{"id":58122,"date":"2024-06-25T11:06:26","date_gmt":"2024-06-25T11:06:26","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=58122"},"modified":"2024-07-03T17:20:14","modified_gmt":"2024-07-03T17:20:14","slug":"the-binding-capacity-of-the-lead-phytochemical-molecule-yo-cancer-cell-target-proteins-and-its-potential-anticancer-properties-with-respect-to-standard-drugs","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/the-binding-capacity-of-the-lead-phytochemical-molecule-yo-cancer-cell-target-proteins-and-its-potential-anticancer-properties-with-respect-to-standard-drugs\/","title":{"rendered":"The Binding Capacity of the Lead Phytochemical Molecule yo Cancer Cell Target Proteins and its Potential Anticancer Properties with Respect to Standard Drugs."},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

The most commonly\ndiscussed cancer is breast cancer (BC). The current treatment has a short-term\neffect of slowing tumor development. Patients frequently experience relapses\nthe disease1<\/sup>. Cell proliferation and apoptotic pathways fail during\nthis process and cancer takes over. BC is slowed by eating nutritious foods and\nstaying physically fit. Foods high in saturated fat, processed meat and so on\nraise circulating levels of endogenous estrogens, pro-inflammatory cytokines,\nand growth factors. These in turn contribute to the development of breast\ncancer2<\/sup>. Natural fruits and vegetables are high in antioxidants and\nthus protect against the development of BC. Regular consumption of fresh fruits\nand vegetable, triglycerides, soy products and limited consumption of red wine\nand carbohydrates raises polyphenol and fibre levels and provides tumorigenesis\nresistance3<\/sup>.<\/p>\n\n\n\n

In silico<\/em>\/docking approach\nhas been shown to improve the drug discovery process by using free online\nsoftware (s) in less time as well as understanding and estimating the toxicity\nand efficiency of the small molecules or drugs4<\/sup>. The two of the\nqualities directly linked to the primary structure are selectivity and\naffinity. Protein (target) and ligand (drug) interaction will have to overcome\ndifficulties such as toxicity because of non-specific protein binding and\ninsufficient efficacy because of low affinity5<\/sup>. <\/p>\n\n\n\n

Quercetin: The\nhuman diet is high in flavonoids which have promising therapeutic properties\nfor a variety of illnesses, including cancer. The flavonoid quercetin has been\nextensively researched and is found in major amounts in commonly used plants\nsuch as Allium cepa, Brassica, Allium\nsativum, <\/em>spinach and others. According to research, quercetin works well on\nmalaria, inflammations, Alzheimer\u2019s, obesity, and breast cancer on par with\nstandard drugs6<\/sup>. Based on research findings, quercetin inhibits BC\nby preventing signal transduction, encouraging cancer cell apoptosis and\nsuppressing cancer cell proliferation and metastasis7<\/sup>.<\/p>\n\n\n\n

Anastrozole:\nAromatase inhibitors of type II are non-steroids and anastrozole is a type II\npotent aromatase inhibitor. Anastrozole binds to the heme ion of aromatase in a\nreversible manner, lowers the levels of estrone (E1), 17-beta-estradiol (E2)\nand estrone sulphate (E1S). Aromatase inhibitors are the endocrine therapy of\nchoice for treating breast cancer, particularly in postmenopausal women.\nAnastrozole is the first-line treatment choice for metastatic situations and\npostmenopausal women with oestrogen receptor-positive BC8<\/sup>.<\/p>\n\n\n\n

Capecitabine: Synonym Xeloda, is a fluoropyrimidine deoxynucleoside\ncarbamate antimetabolic drug. In in-vivo<\/em> conditions, thymidine phosphorylase (dThdPase)\nconverts this drug to 5-fluorouracil (5-FU). It is far more effective as an\nadjuvant treatment in metastasis and in advanced BC, also referred to as a\nrescue drug. It can be effective when combined with other medications9<\/sup>.<\/p>\n\n\n\n

The benefits of combination therapy include improved or maintained efficiency, dose and toxicity reduction; and a delay in the development of drug resistance. In our previous study10<\/sup>, we established that a very low dose of quercetin (16 g\/ml) inhibited cell growth, while increasing cell death, arresting cell cycle, inducing mitochondrial depolarization, and expressing caspase in combination with anastrozole and capecitabine. The current study backs up these findings by docking various BC proteins with the three drugs and comparing their efficacy in binding to the targets. Anti-apoptotic proteins, hydrolases, isomerases, oxidoreductases, transcription factors, binding proteins, signaling proteins, and transferases are all included in this category.<\/p>\n\n\n\n

Material and Methods<\/strong><\/p>\n\n\n\n

CB dock was used\nto dock the drugs (anastrozole, capecitabine,\nand quercetin) with the target proteins. Each target protein was docked\nseparately on each of the three ligands. A total 117 proteins were docked. The\nselected target molecules majorly belong to oxidoreductases\/oxidoreductase\ninhibitors, hydrolases\/hydrolase inhibitors, isomerases, kinase\/kinase\ninhibitors, transferase\/transferase inhibitors, hormone, and cell cycle\ntranscription factors, growth factor receptors, apoptosis regulators, and\nsignaling proteins.  Small molecules\u2019\ninteraction with targets enables biological functions, interpretation, prediction and drug development process. Blind docking\naids in determining the precise binding sides of proteins and predicts the bind\nposes of any given molecule.<\/p>\n\n\n\n

SwissADME<\/strong><\/p>\n\n\n\n

In silico <\/em>methods predict Absorption, Distribution, Metabolism, and Excretion (ADME) parameters based on available molecular structure. The Swiss ADME web tool, which is simple to use, assisted in predicting the physicochemical functions, medicinal chemistry, water solubility, drug-likeness, lipophilicity, and pharmacokinetics. To obtain all these mentioned parameters, the smiles from PubChem for Anastrozole, capecitabine, and quercetin were copied and submitted on the SwissADME page. Following completion, the \u201cBOILED-Egg\u201d button was pressed to record the key parameters of gastrointestinal absorption and blood-brain barrier (BBB)11<\/sup>. <\/p>\n\n\n\n

Drug likeness<\/strong><\/p>\n\n\n\n

Drug\nlikeness provides a balance between molecule properties and structure,\ndetermines the likelihood of a small molecule becoming an oral drug, and\nidentifies the similarities to known drugs. This tool provides molecular\nformula, number of (hydrogen) bond donors and acceptors (HBA and HBD), logP,\nlogS, pKA value, molecular weight, BBB, and likeness score after entering the\nsmiles. The higher the probability, the higher the score value of an active\ndrug. The water partition coefficient predicts an oral drug\u2019s water solubility.\nHigh potency at the biological target is a required quality in drug candidate\npotency. It summarizes the ligand and lipophilic efficiencies. The number of\n(hydrogen) bonds versus side chains (alkyl) of a molecule is used to calculate\nsolubility factor. Slower absorption and action result from lower solubility.\nToo many hydrogen bonds result in low-fat solubility and a failure to penetrate\nthe cell membrane and act inside the cell. The LogP value should be between 0.4\nand 5.6, the molecular weight should be from 160 to 480\/ mol, and the molar\nrefractivity should be from 40 to 130 with 20 to 70 atoms. The drug molecules\u2019\nmolecular properties and drug likeness were provided by MolSoft L.L.C.\nsoftware12<\/sup>. <\/p>\n\n\n\n

Lipinski\u2019s\nrule<\/strong><\/p>\n\n\n\n

The \u201cRule of five\n(RO5)\u201d or \u201cLipinski\u2019s rule\u201d determines whether a predicted molecule adheres to\nfive rules: molecular weight (<500 g\/mol), hydrophobicity (Log P<\/em> <5), HBA (no. <10), HBD (no.\n<5), Polar Surface Area (PSA) (\u2264140 A\u02da) and rotatable bonds (< 10Rot B).\nIt determines the chemical\u2019s oral bioavailability as well as its chemical and\nphysical properties. A molecule is predicted to be a drug should if it meets at\nleast three of the five rules, and a non-oral drug if it violates more than two\nrules13<\/sup>. <\/p>\n\n\n\n

SwissTargetPrediction\n(STP) <\/strong><\/p>\n\n\n\n

This tool\npredicts innate small protein molecule targets. Humans provide the default\nprediction. STP works by providing smile input or by drawing the 2D structure\nprotein probe molecules from PubChem (both synchronise automatically)14,\n15<\/sup>.<\/p>\n\n\n\n

Ligand\nand protein selection<\/strong><\/p>\n\n\n\n

PubChem provided\nthe 3 dimensional (3D) drug structures and isomeric smiles for anastrozole, capecitabine, and quercetin16-19<\/sup>\nand the RCSB protein databank (RCSB PDB) provided the protein targets20<\/sup>.\n<\/p>\n\n\n\n

Docking study<\/strong><\/p>\n\n\n\n

CB-Dock2\nwas used in this study to detect protein surface curvature (CurPocket) and\nguide molecular docking by Auto Dock Vina (1.1.2 version). CB-dock has many\nbenefits over other docking methods21 <\/sup>available. The four steps\ninvolved in quick protein-ligand blind docking are data input and processing;\ncavity detection, visualization and data analysis. CB dock2 examines the ligand\nfor hydrogens, adds hydrogens and partial charges, generates the initial 3D\nconfirmation, adds missing side chain atoms, adds hydrogen atoms, examines the\nmissing residues, and removes the co-crystallized water and hetero groups.<\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

A\nlibrary of targets has been collected from the literature search and structures\nwere retrieved from RCSB. The blind docking method is a model that can be\npreferred for understanding the relation between drug and target at atom\nlevel.  It describes the ability of a\ndrug or small molecule to bind to a target protein.  It is a two-step process that aids in\npredicting ligand confirmation, position, orientation (pose), and affinity\nassessment.<\/p>\n\n\n\n

The\ncurrent study focuses on drug molecule interactions with target proteins in\nBCs. in vitro<\/em> compared the efficiency\nof purified quercetin from radish leaves and dill weed leaves with anastrozole\nand capecitabine. Our findings indicated that quercetin, in conjuction with\nanastrozole and capecitabine, could reduce the toxic burden at a low\nconcentration (16 \u00b5g\/ml)10<\/sup>.<\/p>\n\n\n\n

Docking experiments were conducted to determine which of the three drugs (anastrozole, capecitabine and quercetin) had the highest binding efficiency (Table 1). The protein targets were classified and docked against the three drug molecules using SwissTarget predictions and published literature.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Table 1: The 3 dimensional structure, molecular weight, formula and canonical smiles of the selected drug.<\/strong><\/p>\n

<\/p>\n

Click here to view Table<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Molecular\nweight <5 denotes the light weight of the molecules, that can pass through\nthe target cell\u2019s membrane. Lower MW favours oral absorption, and higher\nmolecules choose an alternate route namely through the membranes. The table\nshows the molecular weight of the selected compounds according to Lipinski\u2019s\nrule. The test compound\u2019s bioavailability radar revealed an immediate\nconsideration of drug-likeness (Table 2 and Fig. 1). XlogP (between -0.7 and\n+5.0), MW (between 150 and 500 g\/mol), polarity (TPSA: between 20 and 130 \u00c5; a little higher for quercetin), solubility (Logs: <6), flexibility\n(rotatable bonds: <9) are the six major properties considered22<\/sup>.<\/p>\n\n\n\n

Table 2: Physicochemical properties of anastrozole, capecitabine and quercetin from SwissADME<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Property<\/strong><\/p>\n<\/td>\n

\n

Anastrozole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Molecular weight (g\/mol)<\/p>\n<\/td>\n

\n

293.37<\/p>\n<\/td>\n

\n

359.35 g\/mol<\/p>\n<\/td>\n

\n

302.24 g\/mol<\/p>\n<\/td>\n<\/tr>\n

\n

Fraction Csp3<\/p>\n<\/td>\n

\n

0.41<\/p>\n<\/td>\n

\n

0.67<\/p>\n<\/td>\n

\n

0.00<\/p>\n<\/td>\n<\/tr>\n

\n

Number of rotatable bonds<\/p>\n<\/td>\n

\n

4<\/p>\n<\/td>\n

\n

8<\/p>\n<\/td>\n

\n

1<\/p>\n<\/td>\n<\/tr>\n

\n

Number of HBA<\/p>\n<\/td>\n

\n

4<\/p>\n<\/td>\n

\n

8<\/p>\n<\/td>\n

\n

7<\/p>\n<\/td>\n<\/tr>\n

\n

Number of HBD<\/p>\n<\/td>\n

\n

0<\/p>\n<\/td>\n

\n

3<\/p>\n<\/td>\n

\n

5<\/p>\n<\/td>\n<\/tr>\n

\n

TPSA<\/p>\n<\/td>\n

\n

78.29 \u00c5<\/p>\n<\/td>\n

\n

122.91 \u00c5<\/p>\n<\/td>\n

\n

131.36 \u00c5<\/p>\n<\/td>\n<\/tr>\n

\n

XLogP3 (lipophilicity)<\/p>\n<\/td>\n

\n

2.03<\/p>\n<\/td>\n

\n

0.56<\/p>\n<\/td>\n

\n

1.54<\/p>\n<\/td>\n<\/tr>\n

\n

Log S (ESOL)<\/p>\n<\/td>\n

\n

-3.04<\/p>\n<\/td>\n

\n

-2.07<\/p>\n<\/td>\n

\n

-3.16<\/p>\n<\/td>\n<\/tr>\n

\n

GI absorption<\/p>\n<\/td>\n

\n

High<\/p>\n<\/td>\n

\n

High<\/p>\n<\/td>\n

\n

High<\/p>\n<\/td>\n<\/tr>\n

\n

BBB permeant<\/p>\n<\/td>\n

\n

Yes<\/p>\n<\/td>\n

\n

No<\/p>\n<\/td>\n

\n

No<\/p>\n<\/td>\n<\/tr>\n

\n

Lipinski<\/p>\n<\/td>\n

\n

0 violation<\/p>\n<\/td>\n

\n

0 violation<\/p>\n<\/td>\n

\n

0 violation<\/p>\n<\/td>\n<\/tr>\n

\n

Synthetic accessibility<\/p>\n<\/td>\n

\n

2.21<\/p>\n<\/td>\n

\n

4.67<\/p>\n<\/td>\n

\n

3.23<\/p>\n<\/td>\n<\/tr>\n

\n

Lead-likeness<\/p>\n<\/td>\n

\n

Yes<\/p>\n<\/td>\n

\n

No<\/p>\n<\/td>\n

\n

Yes<\/p>\n<\/td>\n<\/tr>\n

\n

Bioavailability<\/p>\n<\/td>\n

\n

0.55<\/p>\n<\/td>\n

\n

0.55<\/p>\n<\/td>\n

\n

0.55<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 1: The bioavailability radar from Swiss ADME is presented. A: Anastrozole, B: Capecitabine, C: Quercetin<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

The \u201cBOILED-Egg\u201d graphical output predicts two important ADME parameters at the same time: passive gastrointestinal absorption and BBB15<\/sup>. While the area in the figure represents passive absorption by GI track (Capecitabine and Quercetin), the yolk region (Anastrozole) has higher probability of penetrating the brain (Fig. 2).  <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Boiled egg graphical prediction of ADME parameters at the same time<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

The\nmolecular properties of Ana, Cap, and Que were predicted using MolSoft. The\noutcomes are predicted in (Fig. 3). Green and blue lines represent non-drug and\ndrug-like behavior. Non-drug peaks are those with values between zero and\nnegative. Based on their drug-likeness scores, among the three, Capecitabine\n(positive value of 0.40) and Quercetin (positive value of 0.52) were considered\ndrug molecules, whereas Anastrozole appears to be a non-drug (-0.95).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 3: Plotted drug likeness scores of Anastrazole, Capecitabine and<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

To\nmodify the action of macromolecule targets, drugs or bioactive molecules shall\nbind to them. The mapping of targeted bioactive small molecules is an important\nstep in understanding the molecular actions behind their activity and\nforecasting cross reactivity or potential side effects. The targeted classes\nfor the three drugs tested were provided by SwissTargetPrediction (Fig. 4). The\nchoice of a protein for docking research is critical, particularly its\nresolution. A crystal structure contains either protein or nucleic acid. The\nobtained data from these crystals is the measure of resolution. Majorly, the\ncrystallographic structures have resolution values between 1 \u00c5 and 3 \u00c5.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 4: Swiss Target Prediction of the three drugs and their classes in percentages<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Apoptotic\nproteins as targets<\/strong><\/p>\n\n\n\n

A few\nanit-apoptotic proteins will be targeted to gain insight into the drug\u2019s mode\nof action. With a few exceptions, anastrozole had higher vina scores than the\nother two with apoptotic proteins studied in the present work (Tables 3 and 4,\nFig. 5).<\/p>\n\n\n\n

Table 3: Apoptosis target classes used in the present study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Sl.No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

CASP8 and FADD-like apoptosis regulator<\/p>\n<\/td>\n

\n

3H13<\/p>\n<\/td>\n

\n

272<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-6; C:-6.8; Q:-6.9<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

Apoptosis regulator Bcl-X<\/p>\n<\/td>\n

\n

2YXJ<\/p>\n<\/td>\n

\n

181<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-7.4; C:-6.9; Q:-7.2<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

Apoptosis regulator Bcl-2<\/p>\n<\/td>\n

\n

2O2F<\/p>\n<\/td>\n

\n

138<\/p>\n<\/td>\n

 <\/td>\n\n

A:-7.2; C:-6.9; Q:-7.1<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

Apoptosis regulator Bcl-2, Bcl-2-like protein 1 chimera<\/p>\n<\/td>\n

\n

4IEH<\/p>\n<\/td>\n

\n

169<\/p>\n<\/td>\n

\n

2.10 \u00c5<\/p>\n<\/td>\n

\n

A:-7.7; C:-6.8; Q:-7.2<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

Apoptosis inhibitor survivin<\/p>\n<\/td>\n

\n

1E31<\/p>\n<\/td>\n

\n

142<\/p>\n<\/td>\n

\n

2.71 \u00c5<\/p>\n<\/td>\n

\n

A:-7.1; C:-7.5; Q:-7.5<\/p>\n<\/td>\n<\/tr>\n

\n

6.      <\/p>\n<\/td>\n

\n

Apoptosis regulator Bcl-2<\/p>\n<\/td>\n

\n

2W3L<\/p>\n<\/td>\n

\n

144<\/p>\n<\/td>\n

\n

2.10 \u00c5<\/p>\n<\/td>\n

\n

A:-7.5; C:-7.7; Q:-7.4<\/p>\n<\/td>\n<\/tr>\n

\n

7.      <\/p>\n<\/td>\n

\n

Apoptosis regulator Bcl-X<\/p>\n<\/td>\n

\n

2YXJ<\/p>\n<\/td>\n

\n

181<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-7.5; C:-6.9; Q:-7.1<\/p>\n<\/td>\n<\/tr>\n

\n

8.      <\/p>\n<\/td>\n

\n

Mcl-1<\/p>\n<\/td>\n

\n

3KZ0<\/p>\n<\/td>\n

\n

158<\/p>\n<\/td>\n

\n

2.35 \u00c5<\/p>\n<\/td>\n

\n

A:-7.1; C:-6.2; Q:-6.6<\/p>\n<\/td>\n<\/tr>\n

\n

9.      <\/p>\n<\/td>\n

\n

Bcl-2-like protein 1<\/p>\n<\/td>\n

\n

3ZLN<\/p>\n<\/td>\n

\n

181<\/p>\n<\/td>\n

\n

2.29 \u00c5<\/p>\n<\/td>\n

\n

A:-9.1; C:-7.9; Q:-7.9<\/p>\n<\/td>\n<\/tr>\n

\n

10.   <\/p>\n<\/td>\n

\n

Induced myeloid leukemia cell differentiation protein Mcl-1<\/p>\n<\/td>\n

\n

5IEZ<\/p>\n<\/td>\n

\n

159<\/p>\n<\/td>\n

\n

2.60 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9; C:-7.7; Q:-8.5<\/p>\n<\/td>\n<\/tr>\n

\n

11.   <\/p>\n<\/td>\n

\n

Apoptosis regulator Bcl-2<\/p>\n<\/td>\n

\n

1GJH<\/p>\n<\/td>\n

\n

166<\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n<\/td>\n

\n

A:-6.2; C:-6.2; Q:-6.9<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

\u00c5: Angstrom; CASP: Caspase; FADD: Fas-associated\ndeath domain; Bcl-X: <\/strong>B-cell lymphoma extra; Bcl 2:B-cell\nlymphoma 2; Mcl-1: Induced myeloid leukemia cell differentiation\nprotein<\/p>\n\n\n\n

Table 4: Contact amino acids and varieties of bonds between the target and the ligand molecules belong to apoptotic proteins involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/p>\n<\/td>\n

\n

Contact residues, bond pattern and number of bonds<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

3H13<\/p>\n<\/td>\n

\n

SER318GLN3
19PRO332L
EU333HIS334AR
G337TRP403L
EU405TRP466<\/p>\n

Weak (2), hydrophobic (5)<\/p>\n<\/td>\n

\n

GLY317SER318
GLN319 LEU405
CYS406THR407
ASN447MET450
TYR451ASN454
TYR463TYR464
VAL465TRP466<\/p>\n

Weak (3),
Hydrogen (8),
Hydrophobic (5)<\/p>\n<\/td>\n

\n

ASN262 TYR360SER411
LEU412 LEU413GLN41
5SER416SER419PRO42
0SER421LEU42GLN42
5TYR449TRP453TYR463<\/p>\n

Weak (3), Hydrogen (9),
hydrophobic (9)<\/p>\n<\/td>\n<\/tr>\n

\n

2YXJ<\/p>\n<\/td>\n

\n

THR344LYS345A
SN346ASP348GL
N351ASP354
GLN307THR
308TYR311ASP312
GLU356ASP357TR
P358PHE368LYS37
4LYS376 LYS379<\/p>\n

Weak (1), hydrogen
(1), hydrophobic,
(15)pi-pi (1)<\/p>\n<\/td>\n

\n

SER164
ARG165ALA168
ALA171
THR172TYR120PHE123
GLU124
VAL127ASN128
PHE131 ARG132
ASP133GLY134
VAL135TRP169
THR172TYR173
ASP176HIS177<\/p>\n

Weak (3),
hydrogen (5),
hydrophobic (14),
ionic (2)<\/p>\n<\/td>\n

\n

TYR120PHE123GLU
124GLN125VAL127
ASN128TRP169THR
172TYR173ASP176HI
S177PRO116GLY117T
YR120ARG165TRP169<\/p>\n

Hydrogen (3), hydrophobic
(10), pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

2O2F<\/p>\n<\/td>\n

\n

PHE101TYR105
ASP108PHE109
MET112VAL130
GLU133LEU134
GLY142ARG143
ALA146PHE147
PHE150<\/p>\n

Hydrophobic (9)<\/p>\n<\/td>\n

\n

PHE101ASP108
PHE109MET112
VAL130GLU133
LEU134PHE135
ARG136ASP137
ARG143ALA146
PHE147 PHE150<\/p>\n

Hydrophobic (15),
hydrogen (2), weak (1),
ionic (1)<\/p>\n<\/td>\n

\n

GLN96ALA97GLY
98ASP100PHE101
ARG104TYR105ASP
108TRP141GLY142
ARG143VAL145<\/p>\n

Hydrophobic (7),
pi-pi (1),weak (1),
Hydrogen (2)<\/p>\n<\/td>\n<\/tr>\n

\n

4IEH<\/p>\n

\n<\/p><\/td>\n

\n

PHE63TYR67ASP70
PHE71MET74VAL92
GLU95LEU96GLY
104ARG105ALA
108PHE109GLU111
PHE112VAL115<\/p>\n

Pi-pi (1), weak
(1), Hydrophobic (14)<\/p>\n<\/td>\n

\n

ALA59ASP62
PHE63ARG66<\/p>\n

TYR67LEU96ASN
102TRP103GLY104
ARG105VAL107
ALA108PHE157TYR161<\/p>\n

Pi-pi (1), weak (1),
hydrophobic (15),
ionic (2) Hydrogen (2)<\/p>\n<\/td>\n

\n

PHE63ASP70PHE
71MET74VAL92GL
U95LEU96PHE97
ARG105ALA108PH
E109GLU111PHE112<\/p>\n

VAL115<\/p>\n

Pi-pi (1), weak (3),
Hydrophobic (9),
Hydrogen (2)<\/p>\n<\/td>\n<\/tr>\n

\n

1E31<\/p>\n

\n<\/p><\/td>\n

\n

PHE13 LEU14LYS15
ARG18GLU40PHE
58PHE86VAL89
LYS91GLN92PHE93
GLU94LEU96LEU104<\/p>\n

Hydrogen (3),
hydrophobic (5),
pi-pi (2), ionic (1)<\/p>\n<\/td>\n

\n

PHE13LEU14LYS
15ASP16ARG18GLU
40ILE74LYS78PHE86
LEU87SER88VAL89LY
S90LYS91GLN92PHE93<\/p>\n

Hydrogen (7),
hydrophobic (5),
weak (1)<\/p>\n<\/td>\n

\n

PRO12PHE13L
EU14LYS15ARG
18GLU40ILE74LY
S78PHE86LEU87S
ER88VAL89LYS90
LYS91GLN92PHE
93LEU96<\/p>\n

Hydrogen (7),
hydrophobic (4),
weak (3), ionic (1),
pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

2W3L<\/p>\n<\/td>\n

\n

LYS22ARG26SER
64ARG65ARG68
PHE71SER75GLU111
GLY114VAL115VAL
18GLU119ASN122ASP
62ARG66TYR67<\/p>\n

Hydrogen (2),
hydrophobic (6),
weak (1), ionic (1),
cation pi (1)<\/p>\n<\/td>\n

\n

LYS22ARG26SER64
PHE71SER75GLU111
VAL115VAL118ALA59
ASP62PHE63ARG66
TYR67GLY104
VAL107TYR161<\/p>\n

Hydrogen (7),
hydrophobic (13),
ionic (1)<\/p>\n

<\/p>\n<\/td>\n

\n

LYS22ARG26
ASP61SER64A
RG65ARG68PHE
71ALA72SER75
VAL115VAL118
GLU119ASN122
ARG66<\/p>\n

Hydrogen (7),
hydrophobic (3),
weak (3)<\/span><\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3KZ0<\/p>\n<\/td>\n

\n

GLN189ALA190
GLN221ARG222
GLU225GLN229
LEU232PHE273
LYS276HIS277
LYS279THR280<\/p>\n

Hydrogen (5),
hydrophobic (7),
weak (1), ionic (1)<\/p>\n

<\/p>\n<\/td>\n

\n

GLN189ALA190
THR191LEU232
PHE273LYS276
HIS277LYS279
THR280ASN282
GLN283<\/p>\n

Hydrogen (3),
hydrophobic (8)
weak (4)<\/p>\n

<\/p>\n<\/td>\n

\n

ARG187THR191
LYS279GLN283
GLU284SER285
CYS286ILE287
GLU288ARG187
ALA190THR191
GLU240LYS279
GLN283GLU284
SER285CYS286
ILE287<\/p>\n

Hydrogen (11),
hydrophobic (4),
weak (7)<\/p>\n<\/td>\n<\/tr>\n

\n

3ZLN<\/p>\n<\/td>\n

\n

PHE97ARG102
PHE105SER106
ASP107LEU108
THR109GLU129
LEU130ARG132
GLY138ARG139
ALA142SER145<\/p>\n

PHE146<\/p>\n

Hydrogen (2), ionic (3),
hydrophobic (11),pi-pi
(1), weak (1)<\/p>\n<\/td>\n

\n

LYS16LYS20PHE97
GLU98ARG102ARG
103PHE105SER106
ASP107LEU108THR
109LEU130ALA142
SER145PHE146GLY
148ALA149<\/p>\n

Ionic (3), weak (4),
hydrogen (6),hydrophobic
(13),cation pi (1)<\/p>\n<\/td>\n

\n

LYS20PHE97
GLU98LEU99
ARG102ARG103
ASP107LEU108
THR109LEU130
ALA142PHE143
SER145PHE146
ALA149<\/p>\n

Ionic (2), cation
(1),Hydrogen (8),
hydrophobic (11),
weak (1)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

5IEZ<\/p>\n<\/td>\n

\n

HIS224ALA227
PHE228MET231
LEU235LEU246
VAL249MET250
VAL253PHE254
ARG263THR266
LEU267PHE270<\/p>\n

Hydrogen (20,
weak (1),
hydrophobic (13)<\/p>\n<\/td>\n

\n

ASN239GLU240
ASN282GLN283GLU
284SER285CYS286
ChainB:GLU173
ARG176GLN177
LEU179GLU180
SER183ARG184
GLY200ARG201
SER202GLU288<\/p>\n

Hydrogen (7),
hydrophobic (4),
weak (5)<\/p>\n<\/td>\n

\n

ASN239GLU240
LYS279ASN282
GLN283GLU284
SER285ChainB:
ASP172GLU173
TYR175ARG176G
LN177LEU179GL
U180SER183ARG
184GLY200ARG20
1SER202 GLU288<\/p>\n

Hydrophobic (3),
weak (4),
Hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

1GJH<\/p>\n<\/td>\n

\n

HIS3ALA4GLY
5ARG6THR7
GLY8TYR9HIS
186GLN190GLY
193GLY194TRP
195ASP196
ALA197<\/p>\n

Hydrogen (2), cation pi (1), hydrophobic (7)<\/p>\n<\/td>\n

\n

HIS3ALA4GLY
5TYR9ASP10A
SN11ASN182HIS
186ILE189GLN
190GLY193 GLY194TRP195<\/p>\n

Pi-pi (1), hydrogen (6) hydrophobic (5)<\/p>\n<\/td>\n

\n

HIS3ALA4GLY5
GLY8TYR9ASP
10ASN11HIS186
ILE189GLN190
GLY193GLY194
TRP195ASP196
ALA197<\/p>\n

Hydrogen (3),
pi-pi (1), hydrophobic (2)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 5: Docking profile of protein and ligand binding of the apoptotic proteins studied.  Ana: Anastrazole, Cap: Capecitabine and Que: Quercetin<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Tumor\ncells escape, protect and develop drug resistance by avoiding receptor mediated\napoptosis. C-FLIP (Cellular FLICE like inhibitory protein) is a key regulator\nprotein in the extrinsic cell death pathway (FADD-like IL-1beta-converting\nenzyme inhibitory protein). Overexpression of c-FLIP protects the tumor cells.\nThis is a capable caspase activation initiator and cell death inhibitor as well\nas an enhancer of procaspase-8 activation. Bcl-2 and Bcl-xL overexpression in\ncancer cells confers a survival benefit over standard chemotherapy\n(anti-apoptotic or pro-survival proteins). Survivin, a mitotic spindle\nfiber-associated protein, acts as an apoptosis activator. Myeloid cell\nLeukemia-1 is a Bcl-2 anti-apoptotic member. Anti-apoptotic protein\nover-expression promotes cell survival and proliferation. Targeting these\nproteins will aid in the development of new drugs and drug combinations20<\/sup>.\n<\/p>\n\n\n\n

Hydrolases as targets<\/strong><\/p>\n\n\n\n

The vina scores\nof quercetin seem to be the highest among the three drugs tested by docking for\nhydrolases (Tables 5, 6) (Fig. 6)20<\/sup>. DPP-4 is a cell surface protein that either suppresses or\nactivates tumors. MMP-9 is essential in inflammatory and oncological\ndisorders.  ADAMTSs\nare members of extracellular zinc metalloproteinase family. Chemokine receptors\nare cell migration receptors linked to cancer metastasis. VEGF is a type of\nangiogenesis factor. Chemokine receptors regulate cell migration, cancer,\nimmune responses, inflammation, and so on. Butyrylcholinesterase (BChE) and its\ngenes are found in a variety of human cancers. Tumorigenesis, cell\nproliferation, and cell differentiation have all linked to it. DHS36 interacts\nwith RNA and DNA G-quadruples to control transcription and post-transcriptional\nregulation. Cysteine protease relates to the mammalian interleukin-1 beta\nconverting enzyme (ICE). Caspases, the cysteine proteases, are key role players\nin apoptosis and inflammation. MMP-9 is a protein that is participates in\ninflammation, wound healing, tumour growth and metastasis20<\/sup>.<\/p>\n\n\n\n

Table 5: Hydrolases target classes used in the present study<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Sl.No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

Dipeptidyl peptidase 4 soluble form<\/p>\n<\/td>\n

\n

4A5S<\/p>\n<\/td>\n

\n

740<\/p>\n<\/td>\n

\n

1.62 \u00c5<\/p>\n<\/td>\n

\n

A:-8;C:-7.2;Q:-9<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

Matrix metalloproteinase-9,<\/p>\n<\/td>\n

\n

5TH6<\/p>\n<\/td>\n

\n

231<\/p>\n<\/td>\n

\n

1.70 \u00c5<\/p>\n<\/td>\n

\n

A:-7.3;C:-7.0;Q:-8.6<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

A disintegrin and metalloproteinase with thrombospondin motifs 4<\/p>\n<\/td>\n

\n

4WKE<\/p>\n<\/td>\n

\n

235<\/p>\n<\/td>\n

\n

1.62 \u00c5<\/p>\n<\/td>\n

\n

A:-7.4;C:-7.5;Q:-8.6<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

C-X-C chemokine receptor type 4, Lysozyme Chimera<\/p>\n<\/td>\n

\n

3OE0<\/p>\n<\/td>\n

\n

499<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9;C:-8.1;Q:-8.2<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

protein (vascular endothelial growth factor)<\/p>\n<\/td>\n

\n

1VPP<\/p>\n<\/td>\n

\n

102<\/p>\n<\/td>\n

\n

1.90 \u00c5<\/p>\n<\/td>\n

\n

A:-6.5;C:-6.6;Q:-6.7<\/p>\n<\/td>\n<\/tr>\n

\n

6.      <\/p>\n<\/td>\n

\n

NHE-RF1<\/p>\n<\/td>\n

\n

4JL7<\/p>\n<\/td>\n

\n

91<\/p>\n<\/td>\n

\n

1.16 \u00c5<\/p>\n<\/td>\n

\n

A:-6.7;C:-6.2;Q:-6.7<\/p>\n<\/td>\n<\/tr>\n

\n

7.      <\/p>\n<\/td>\n

\n

Apopain<\/p>\n<\/td>\n

\n

1PAU<\/p>\n<\/td>\n

\n

147<\/p>\n<\/td>\n

\n

2.50 \u00c5<\/p>\n<\/td>\n

\n

A:-5.8;C:-6;Q:-6<\/p>\n<\/td>\n<\/tr>\n

\n

8.      <\/p>\n<\/td>\n

\n

Caspase-8<\/p>\n<\/td>\n

\n

1QTN<\/p>\n<\/td>\n

\n

164<\/p>\n<\/td>\n

\n

1.20 \u00c5<\/p>\n<\/td>\n

\n

A:-6.7;C:-7.2;Q:-7.2<\/p>\n<\/td>\n<\/tr>\n

\n

9.      <\/p>\n<\/td>\n

\n

Matrix metalloproteinase-9 (EC 3.4.24.35) (MMP-9) (92 kDa type IV collagenase) (92 kDa gelatinase) (Gelatinase B) (GELB)<\/p>\n<\/td>\n

\n

2OVX<\/p>\n<\/td>\n

\n

159<\/p>\n<\/td>\n

\n

2.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.1;C:-8.6;Q:-10.4<\/p>\n<\/td>\n<\/tr>\n

\n

10.   <\/p>\n<\/td>\n

\n

DEAH (Asp-Glu-Ala-His) box polypeptide 36<\/p>\n<\/td>\n

\n

5VHE<\/p>\n<\/td>\n

\n

933<\/p>\n<\/td>\n

\n

3.79 \u00c5<\/p>\n<\/td>\n

\n

A:-8.5;C:-8.4;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

11.   <\/p>\n<\/td>\n

\n

Cholinesterase<\/p>\n<\/td>\n

\n

4BDS<\/p>\n<\/td>\n

\n

529<\/p>\n<\/td>\n

\n

2.10 \u00c5<\/p>\n<\/td>\n

\n

A:-8.9;C:-8.2;Q:-9.3<\/p>\n<\/td>\n<\/tr>\n

\n

12.   <\/p>\n<\/td>\n

\n

C-X-C chemokine receptor type 4, Lysozyme Chimera<\/p>\n<\/td>\n

\n

3ODU<\/p>\n<\/td>\n

\n

502<\/p>\n<\/td>\n

\n

2.50 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-7.9;Q:-8.3<\/p>\n<\/td>\n<\/tr>\n

\n

13.   <\/p>\n<\/td>\n

\n

C-X-C chemokine receptor type 4, Lysozyme Chimera<\/p>\n<\/td>\n

\n

3OE9<\/p>\n<\/td>\n

\n

499<\/p>\n<\/td>\n

\n

3.10 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-7.2;Q:-8.1<\/p>\n<\/td>\n<\/tr>\n

\n

14.   <\/p>\n<\/td>\n

\n

C-X-C chemokine receptor type 4, Lysozyme Chimera<\/p>\n<\/td>\n

\n

3OE8<\/p>\n<\/td>\n

\n

502<\/p>\n<\/td>\n

\n

3.10 \u00c5<\/p>\n<\/td>\n

\n

A:-8.6;C:-7.6;Q:-8.2<\/p>\n<\/td>\n<\/tr>\n

\n

15.   <\/p>\n<\/td>\n

\n

C-X-C chemokine receptor type 4\/Endolysin chimeric protein<\/p>\n<\/td>\n

\n

4RWS<\/p>\n<\/td>\n

\n

498<\/p>\n<\/td>\n

\n

3.10 \u00c5<\/p>\n<\/td>\n

\n

A:-7.5;C:-7.1;Q:-8.2<\/p>\n<\/td>\n<\/tr>\n

\n

16.   <\/p>\n<\/td>\n

\n

Beta-secretase 1<\/p>\n<\/td>\n

\n

4IVT<\/p>\n<\/td>\n

\n

433<\/p>\n<\/td>\n

\n

1.60 \u00c5<\/p>\n<\/td>\n

\n

A:-7.4;C:-7.1;Q:-7.8<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

NHE-RF1: Sodium (+)\/Hydrogen (+) exchange regulatory cofactor 1<\/p>\n\n\n

Table 6: Contact amino acids and varieties of bonds between the target and the ligand molecules belong to hydrolases involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues, bond pattern and number of bonds<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/p>\n<\/td>\n

\n

Quercetin<\/p>\n<\/td>\n<\/tr>\n

\n

4A5S<\/p>\n<\/td>\n

\n

PRO475GLY476
MET509PRO510
SER511LYS512G
LN527ILE529ASP
556VAL558PHE5
59ARG560LEU56
1ASN562ALA564
THR565<\/p>\n

Ionic (2), hydrogen (5),
weak (3), hydrophobic (4)<\/p>\n

<\/p>\n<\/td>\n

\n

GLN314MET325
HIS345ILE346G
LU347ET348SE
R349THR350TH
R351GLY52LYS
373ILE375SER376
ASN377GLU378
GLY380PHE387
LYS392CS394P
HE396ASP588HIS592<\/p>\n

Cation pi (1), ionic (2),
hydrogen (8),  weak (3),
Hydrophobic (9)<\/p>\n<\/td>\n

\n

PRO475GLY476MET
509PRO510SER511
LYS512GLN527ILE5
29ASP556VAL558PH
E559ARG560LEU561
ASN562ALA564THR565
Ionic (2), hydrogen (17),<\/p>\n

Hydrophobic (11), weak (6)<\/p>\n<\/td>\n<\/tr>\n

\n

5TH6<\/p>\n<\/td>\n

\n

ARG143LEU147LEU
212SER394PHE396
LEU397PHE425TH
R426GLU427GLY4
28PRO429PRO430
ARG143LEU212PHE
396PHE425THR426
GLU427GLY428PRO
429PRO430<\/p>\n

Cation pi (2), hydrophobic
(12), weak (2), hydrogen (4)<\/p>\n<\/td>\n

\n

ARG143LEU147
LEU212GLY213
SER394PHE396
LEU397PHE425
THR426GLU427
GLY428PRO429
PRO430LEU431
ARG143ALA146
LEU147ALA150
PHE396GLU427
GLY428PRO429
PRO430LEU431<\/p>\n

Cation pi (2),
hydrophobic (20),
weak (2), hydrogen (3)<\/p>\n<\/td>\n

\n

LEU397VAL398
HIS401PRO415G
LU416ALA417LE
U418MET419TYR
420PRO421MET4
22TYR423ARG424
THR426GLY428PR
O429PRO430HIS432<\/p>\n

Hydrophobic (7),
hydrogen (9)
weak (6)<\/span><\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

4WKE<\/p>\n<\/td>\n

\n

THR326ASP328THR
329LEU330GLY331
THR358HIS361VAL
390ALA392PRO393
VAL394MET395<\/p>\n

Cation pi (3),
hydrogen (4),
weak hydrogen (1),
hydrophobic (5)<\/span><\/p>\n

<\/p>\n<\/td>\n

\n

GLY323ASP328
THR329LEU330
GLY33MET332
PHE357THR358
HIS361GLU362
HIS365HIS371
HIS389VAL390
ALA392PRO393
VAL394MET395
ALA396VAL398<\/p>\n

Hydrogen (9),
weak hydrogen (3),
hydrophobic (8)<\/p>\n<\/td>\n

\n

ASP328THR329
LEU330GLY331
MET332PHE357
THR358HIS361
GLU362HIS365
HIS371HIS389
VAL390MET391
ALA392PRO393
VAL394MET395
ALA396VAL398<\/p>\n

hydrogen (8),
weak hydrogen<\/p>\n

(6), hydrophobic (4),
pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

3OE0<\/p>\n<\/td>\n

\n

ALA137ILE138ALA
141LYS225LEU226
ASN1002GLU1005
VAL1094THR1157T
RP1158ASP1159TYR
1161LYS234 LYS236<\/p>\n

Hydrogen (4),
hydrophobic (6)
weak hydrogen (2)<\/p>\n<\/td>\n

\n

ARG30GLU32ASN33
PHE36ASN37LEU
41ASP97ALA98
ARG183ILE185
CYS186ASP187LY
S282SER285
ILE286ARG1<\/p>\n

Hydrogen (7),
hydrophobic (13),
ionic interaction (4),
weak hydrogen (1)<\/p>\n<\/td>\n

\n

ALA137ILE138
ALA141LEU226
ALA1093VAL1094
GLY1156THR1157
TRP1158ASP1159
GLY231HIS232LYS
234ARG235LYS236
ALA237LEU238<\/p>\n

Hydrogen (9),
pi-pi sticking (1),
hydrophobic (6),
weak hydrogen (5)<\/p>\n<\/td>\n<\/tr>\n

\n

1VPP<\/p>\n<\/td>\n

\n

ASP34ILE35PHE
36TYR39PRO40
GLU42ILE43TYR
45PHE47SER50
GLU64LYS107<\/p>\n

Hydrogen (1),
pi-pi sticking (1),
hydrophobic (9),
ionic interaction (2),
weak hydrogen (1)<\/span><\/p>\n<\/td>\n

\n

GLU64Chain
W:ASP34ILE35
PHE36ILE43GLU
44TYR45ILE46P
HE47SER50CYS51<\/p>\n

Hydrogen (10),
pi-pi sticking (1),
hydrophobic (5),
weak hydrogen (1)<\/p>\n<\/td>\n

\n

ILE35PHE36
TYR39PRO40ASP
41GLU2ILE43TYR
45ILE46PHE47SER
50 PRO85GLU64<\/p>\n

Hydrogen (2),
hydrophobic (9),
<\/span>weak hydrogen (2)<\/p>\n<\/td>\n<\/tr>\n

\n

3OE8<\/p>\n<\/td>\n

\n

LEU41TYR45PHE
93TRP94ASP97AL
A98TRP102VAL112
HIS113TYR116CYS1
86ASP187ARG188
SER285 GLU288<\/p>\n

Hydrogen bond (1),
pi-pi sticking (1),
hydrophobic (4),
ionic interaction (1),
Weak hydrogen (1)<\/span><\/p>\n<\/td>\n

\n

HIS113TYR11
6THR117LEU120
TYR121LEU167ASP
171ARG188TYR190
PHE199GLN200HIS20
3TYR255GLY258ILE
259ASP262SER263
HIS281ILE284GLU288<\/p>\n

Weak hydrogen (2),
ionic interaction (1),
hydrophobic (15),
Hydrogen (8), cation-pi (1)<\/span><\/p>\n<\/td>\n

\n

TYR45PHE93
TRP94ASP97TR
P102CYS109VAL
112HIS113TYR11
6ARG188HIS281
ILE284SER285
GLU288<\/p>\n

Hydrogen (6),
pi-pi sticking (3),<\/p>\n

hydrophobic (6),
weak (2)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

4JL7<\/p>\n<\/td>\n

\n

LYS19ASN22GLY
23TYR24GLY25PHE
26LEU28HIS72VAL
75VAL76ILE79 ARG80<\/p>\n

Weak hydrogen (1),
hydrophobic (7),
cation-pi interaction (1)
hydrogen bond (1)<\/p>\n<\/td>\n

\n

ASN22GLY23TYR
24GLY25PHE26
HIS27LEU28LEU
41GLU43VAL76ILE79<\/p>\n

Weak hydrogen (2),
hydrophobic (6),
hydrogen (3)<\/p>\n

<\/p>\n<\/td>\n

\n

LYS19GLY23TYR24
PHE26HIS27LEU28
HIS72VAL76ILE79
ARG80ALA81ALA
82LEU83 ASN84<\/p>\n

Weak hydrogen (3),
hydrophobic (9),
hydrogen (6),
cation-pi interaction (2),
pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

3OE9<\/p>\n<\/td>\n

\n

LEU41TYR45PHE93
TRP94ASP97TRP102
VAL112HIS113TYR116
CYS186ASP187ARG
188SER285GLU288<\/p>\n

Ionic (2),
hydrophobic (6),
hydrogen (4),
pi-pi (2)<\/p>\n

<\/p>\n<\/td>\n

\n

TRP94ASP97HIS113
TYR116THR117LEU
120TYR121ASP171
ARG183CYS186ASP
187ARG188GLN200
HIS203TYR255GLU288<\/p>\n

Weak hydrogen (6),
ionic interaction (1),
hydrophobic (15),
hydrogen (7)<\/p>\n<\/td>\n

\n

LEU41TYR45TRP94ASP97
ALA98CYS109VAL112HIS
113TYR116ARG183CYS
186ARG188ILE284SER
285ILE286GLU288<\/p>\n

Weak hydrogen (3),
ionic interaction (1),
hydrophobic (4),<\/p>\n

Hydrogen (9),
pi-pi (2)<\/p>\n<\/td>\n<\/tr>\n

\n

4RWS<\/p>\n<\/td>\n

\n

HIS113TYR116
THR117LEU120
TYR121ASP171
ARG188TYR190
VAL196PHE199
GLN200HIS203
LEU1GLY2CYS5<\/p>\n

Weak hydrogen (2),
ionic (3), hydrophobic (7),
hydrogen (7), cation-pi (1)<\/span><\/p>\n<\/td>\n

\n

ALA137ILE138ALA
141THR142LYS225L
EU226ASN1002ILE
1003ALA1093VAL1
094ALA1097TRP11
58ASP1159SER1162
SER1164GLY231LY
S234 LYS236<\/p>\n

Weak hydrogen (2)
hydrophobic (12),
hydrogen (3)<\/p>\n<\/td>\n

\n

HIS113TYR116
THR117LEU120
TYR121ASP171CYS
186CYS187ARG188
TYR190PHE199
GLN200GLN202
HIS203LEU1GLY2CYS5<\/p>\n

Weak hydrogen (2)
hydrophobic (7),
hydrogen (6)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3ODU<\/p>\n<\/td>\n

\n

LEU41TYR45PHE
93TRP94ASP97AL
A98TRP102CYS109
VAL112HIS113TYR
116CYS186ASP187
ARG188SER285GLU288<\/p>\n

Weak hydrogen (1),
ionic (5), hydrophobic (8),
Hydrogen (2), pi-pi (1)<\/p>\n<\/td>\n

\n

GLU31GLU32ASN
33ASN37LYS38LEU
41TYR45TRP94ASP
97ALA98VAL112HI
S113TYR116CYS186
HIS281LYS282SER
285GLU288<\/p>\n

Ionic (1), hydrogen (3)
, hydrophobic (8),
weak hydrogen (5)<\/p>\n<\/td>\n

\n

GLU32LEU41TYR45
PHE93TRP94ASP97
ALA98TRP102VAL
112HIS113TYR116
ARG188SER285<\/p>\n

GLU288<\/p>\n

Hydrogen (4),
hydrophobic (7),
weak hydrogen (1),<\/p>\n

pi-pi (1)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

4BDS<\/p>\n<\/td>\n

\n

ASP70GLY78SER
79TRP82ASN83
GLY115GLY116
GLY117THR120
TYR128GLU197
SER198ALA199
ALA328PHE329
TYR332TRP430
MET437HIS438
GLY439TYR440
ILE442<\/p>\n

Ionic (3), pi-pi (1) hydrophobic(7), weak hydrogen (5), hydrogen (10)<\/p>\n<\/td>\n

\n

TRP82GLY115GLY
116GLY117GLN119
THR120GLU197SER
198ALA199THR284PR
O285LEU286SER287VAL
288ASN289PHE329HIS
438GLY439<\/p>\n

Hydrophobic (14),
weak hydrogen (3),
hydrogen (11)<\/p>\n

<\/p>\n<\/td>\n

\n

GLN67ASN68ILE
69ASP70TRP82AS
N83PRO84TYR114
GLY115GLY116THR
120GLY121TYR128
GLU197SER198TYR
332HIS438GLY439ILE442<\/p>\n

Ionic (1),
hydrophobic (4),
weak hydrogen (5),
hydrogen (10), pi-pi (2)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

5HVE<\/p>\n<\/td>\n

\n

LYS78GLU79GLU
81ARG82ARG85LYS
847TRP887GLN922
THR929TRP935ILE
936ILE937PHE938
GLN939<\/p>\n

Ionic (3), hydrophobic (7),
weak hydrogen (3), hydrogen (4)<\/p>\n<\/td>\n

\n

PHE579ASN584ILE
585SER586THR636
PRO637LEU638GLU
639GLU640GLU701
PRO702PHE729LYS
844HIS891LEU892
LYS893<\/p>\n

MET894<\/p>\n

Ionic (3),
hydrophobic (4),
weak hydrogen (1),
hydrogen (6)<\/p>\n<\/td>\n

\n

LEU343PRO637
LEU638GLU639
GLU640LEU641
GLU701PRO702
HIS703PHE729L
YS844HIS891<\/p>\n

LEU892<\/p>\n

Ionic (1), cation-pi (1),
hydrophobic (7),
weak hydrogen (2),
<\/span>hydrogen (10)<\/p>\n<\/td>\n<\/tr>\n

\n

1PAU<\/p>\n<\/td>\n

\n

THR177HIS237
ChainB:TRP340
ARG341PHE381
SER381PHE381
ASP381PHE381
ASP502GLU503V
AL504<\/p>\n

Hydrogen (6),
ionic (1), cation pi (1),
hydrophobic (6),
weak hydrogen (4)<\/span><\/p>\n<\/td>\n

\n

MET176THR177HIS
237GLY238PHE244
CYS285GLY287THR
288ChainB:TYR338
TRP340SER381ASP381
PHE381ASP502GLU
503VAL504<\/p>\n

Hydrogen (5),
hydrophobic (16),
weak hydrogen (2)<\/p>\n<\/td>\n

\n

ChainA:GLU191THR
192ASN195LEU196
ChainB:LYS358AL
A361ASP362LYS363
PHE400TYR401<\/p>\n

Hydrogen (6),
hydrophobic (9),
<\/span> ionic (1),
weak hydrogen (2)<\/span><\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

1QTN<\/p>\n<\/td>\n

\n

LYS253 LEU254
HIS255<\/p>\n

SER256ILE257
ARG258HIS317
GLY318ASP319
TYR324CYS360
GLY362ASP363
THR503<\/p>\n

Ionic (1), cation pi (2),
weak hydrogen (3),
hydrophobic (11),
hydrogen (3)<\/span><\/p>\n<\/td>\n

\n

LYS320GLY321PRO
332ILE333TYR334
THR337SER338THR
341GLN361GLU396
PHE399LEU401MET
403ASN407GLN465
THR467 THR469<\/p>\n

Hydrogen (10),
hydrophobic (7),
weak hydrogen (5)<\/p>\n<\/td>\n

\n

LYS253LEU254
SER256ILE257
ARG258HIS317
GLY318ASP319
TYR324CYS360
GLY362ARG413
GLU502THR503<\/p>\n

Cation-pi (1),
ionic (1), hydrogen (11),
weak hydrogen (3),
<\/span>hydrophobic (6)<\/p>\n<\/td>\n<\/tr>\n

\n

2OVX<\/p>\n<\/td>\n

\n

GLN126VAL167
GLN169HIS175
GLY176ASP177
GLY197ILE198
ASP201HIS203
TRP124TYR160
SER161ARG162ASP163<\/p>\n

Hydrogen (6),
ionic (4),
hydrophobic (5),
weak hydrogen (2)<\/p>\n<\/td>\n

\n

GLY186LEU187
LEU188ALA189
LEU397VAL398
HIS401GLN402
HIS405HIS411
GLU416ALA417
LEU418TYR420P
RO421MET422TY
R423ARG424THR<\/p>\n

426PRO430<\/p>\n

Hydrophobic (8), hydrogen (3), weak hydrogen (2)<\/p>\n<\/td>\n

\n

LEU188LEU397VAL398
HIS401GLN402PRO415
GLU416ALA417LEU418
TYR420PRO421MET422
TYR423ARG424THR426
GLU427GLY428
PRO429PRO430<\/p>\n

Hydrogen (8), weak hydrogen (3), hydrophobic (7)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 6: Docking poses of hydrolases with the ligannds<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Isomerases as targets<\/strong><\/p>\n\n\n\n

The\nvina scores of quercetin were the highest of the three drugs tested (Tables 7,\n8) (Fig. 7)20<\/sup>. Type IIA DNA topoisomerases are required for the\nmaintenance of higher order DNA structure. The double standard DNA is\ncovalently joined by human topoisomerase I. Type II topoisomerases (TOP2s) cleaves both the DNA duplex and cause\ncancer cell death. Kinase complexed mTOR is an important growth and\nproliferation regulator. DNA topoisomerases, particularly type IIA\ntopoisomerases, have been identified as anti-bacterial and anti-cancer drug\ntargets. Topoisomerase-targeting anticancer drugs work by poisoning\ntopoisomerase, causing replication fork arrest and double-strand break\nformation20<\/sup>.<\/p>\n\n\n\n

Table 7: Isomerases target classes used in the present study<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n
\n

Sl. No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

Peptidyl-prolyl cis-trans isomerase FKBP5<\/p>\n<\/td>\n

\n

4DRH<\/p>\n<\/td>\n

\n

144<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4; C:-8.5;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

DNA topoisomerase 2-beta<\/p>\n<\/td>\n

\n

3QX3<\/p>\n<\/td>\n

\n

803<\/p>\n<\/td>\n

\n

2.16 \u00c5<\/p>\n<\/td>\n

\n

A:-8.5;C:-7.8;Q:-9<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

DNA topoisomerase I<\/p>\n<\/td>\n

\n

1K4T<\/p>\n<\/td>\n

\n

592<\/p>\n<\/td>\n

\n

2.10 \u00c5<\/p>\n<\/td>\n

\n

A:-8.5;C:-8.4;Q:-9.1<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

DNA topoisomerase II, alpha isozyme<\/p>\n<\/td>\n

\n

1ZXM<\/p>\n<\/td>\n

\n

400<\/p>\n<\/td>\n

\n

1.87 \u00c5<\/p>\n<\/td>\n

\n

A:-8.9;C:-8.5;Q:-10.1<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

DNA topoisomerase I<\/p>\n<\/td>\n

\n

1T8I<\/p>\n<\/td>\n

\n

592<\/p>\n<\/td>\n

\n

3.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-8.2;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

FKBP5: FK506-binding protein 5<\/p>\n\n\n

Table 8: Contact amino acids and varieties of bonds between the target and the ligand molecules belong to isomerases involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues and bond pattern<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

IZXM<\/p>\n<\/td>\n

\n

ASN91ALA92
ASP94ASN95
ARG98ASN120
ILE125ILE141
PHE142THR
147SER148SER
149ASN150THR
159GLY161ALA167
LYS168THR
215ILE217 TYR34<\/p>\n

Hydrogen (8),
weak hydrogen(2),
Hydrophobic (12)<\/p>\n<\/td>\n

\n

TYR34GLU87ASN
91ASP94ASN95ARG
98ILE125ILE141PHE
142THR147SER148SER<\/p>\n

149ASN150THR159
GLY161ARG162ASN
163GLY164TYR165
GLY166ALA167LYS168
GLN376LYS378<\/p>\n

Hydrogen (13),
weak hydrogen (5),
ionic (1) hydrophobic (8)<\/p>\n<\/td>\n

\n

ASN91ALA92ASP94
ASN95ARG98ASN120
LYS123GLY124ILE125
ILE141PHE142THR147
SER148SER149ASN150
GLY164ALA167LYS168
THR181TYR214THR215<\/p>\n

Hydrogen (19),
weak hydrogen (6),
hydrophobic (6)<\/p>\n<\/td>\n<\/tr>\n

\n

1K4T<\/p>\n<\/td>\n

\n

LYS354ILE355GLU
356PRO357PRO358
PHE361LYS374ARG
375ARG376ILE377TR
P416GLU418ASN419I
LE420SER423 LYS425TYR426<\/p>\n

Hydrogen (3),
hydrophobic (8),
weak hydrogen (3),
ionic (2), pi-pi (3)<\/span><\/p>\n<\/td>\n

\n

LYS202TRP203LYS
204TRP205TRP206
LYS347GLU348ARG
349ASN430SER432SER
433ARG434ARG749
GLU750ALA753ILE756<\/p>\n

ASP757<\/p>\n

Hydrogen (27),
hydrophobic (9),
weak hydrogen (10),
ionic (1) (1), pi-pi (16)<\/p>\n<\/td>\n

\n

ASN352LYS354ILE355 GLU356<\/p>\n

PHE361LYS374
ARG375ILE377
TRP416GLU418
ASN419ILE420
LYS425TYR426ILE427<\/p>\n

Hydrogen (24),
hydrophobic (5),
weak hydrogen (11),
ionic (2), pi-pi (11)<\/p>\n<\/td>\n<\/tr>\n

\n

3QX3<\/p>\n<\/td>\n

\n

ARG503GLY776
GLU777GLN778
ALA779MET782<\/p>\n

Weak hydrogen (2),
hydrgoen (9),
hydrophobic (3),  
pi-pi (4)<\/p>\n<\/td>\n

\n

GLU477GLY
478ASP479LEU
502ARG503GLY
504MET782<\/p>\n

Weak hydrogen (7),
hydrogen (19),
hydrophobic (3),
pi-pi (4)<\/p>\n<\/td>\n

\n

LYS456GLY478
ASP479SER480
LEU502ARG503
GLY504GLN778
MET782<\/p>\n

Weak hydrogen (11),
hydrogen (16),
Hydrophobic (1),
pi-pi (4), ionic (1)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

4DRH<\/p>\n<\/td>\n

\n

TYR57PHE67ASP
68HIS71PHE77
TYR113PRO120
PHE130Chain
E:SER2035TYR
2038PHE2039LEU
2097THR2098TRP
2101ASP2102TYR2105<\/p>\n

Ionic (2), hydrogen
(1), weak hydrogen
(3), hydrophobic (10)<\/p>\n<\/td>\n

\n

TYR57ASP68SER
70HIS71PHE77
PRO120Chain
E:LEU2031GLU
2032SER2035
PHE2039LEU
2097THR2098
TRP2101ASP2102
TYR2104TYR2105
PHE2108<\/p>\n

Ionic (1), hydrogen (5),
weak hydrogen (4),
Hydrophobic (15), pi-pi (1)<\/p>\n<\/td>\n

\n

ASP68HIS71PHE
77VAL78GLN85
ChainB:LEU2031
GLU2032SER2035
PHE2039LEU2097
THR2098GLN2099
TRP2101ASP2102TYR
2104TYR2105PHE2108<\/p>\n

Ionic (2), hydrogen (4),
weak hydrogen (5),
Hydrophobic (8),  pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

1T81<\/p>\n<\/td>\n

\n

ASN352LYS354ILE
355GLU356PRO357
PRO358PHE361LYS374
ARG375ILE377TRP416
GLU418ASN419
LYS425TYR426<\/p>\n

Weak hydrogen (4), hydrogen (16), ionic (2), pi-pi (9), hydrophobic (8)<\/p>\n<\/td>\n

\n

ILE355GLU356PRO
357PRO358PHE361
GLY363ARG364HIS
367LYS374ARG375
ILE377TRP416GLU
418ASN419ILE420
GLN421SER
423LYS425<\/p>\n

Weak hydrogen(6), hydrogen (21), ionic (2), pi-pi (11), hydrophoic (12)<\/p>\n<\/td>\n

\n

ASN352GLU356PR
O357LEU373LYS374
ARG375ARG376ILE
377TRP416GLU418
ASN419ILE420LYS
425TYR426ILE427<\/p>\n

Weak hydrogen (6),
hydrogen (18), ionic (1),
pi-pi (13), hydrophobic (4)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\nFigure 7: Interaction between the isomerase targets and ligands.<\/strong><\/strong>

<\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Oxidoreductases as targets<\/strong><\/em><\/p>\n\n\n\n

The vina score of quercetin is the highest\namong the tested drugs against the goals of oxidoreductases (Tables 9, 10)\n(Fig. 8)20<\/sup>. Myeloperoxidase (MPO), a\nneutrophilic enzyme, promotes oxidative stress in a number of inflammatory\npathologies. Catalysis of human cytochrome P450 aromatase enzyme results to\nform estrogens from androgens. Human Aldehyde\ndehydrogenase 1A3\u2019s expression is more in cancers. COX\ntakes charge of the increased production of prostaglandins during inflammation.\nP450 1A2 is accountable for the activation\nof carcinogenic compounds. Increased GSH levels in tumor cells are linked to\ntumor progression and resistance to chemotherapeutic drugs. Cancer cells show\nelevated levels of FTO expression. eNOS is involved in promotion or inhibition\nof cancer etiology. Cyclooxygenase 1 is an anti-inflammatory responsive enzyme.\nAromatase inhibitors are thus first-line therapy for estrogen-dependent breast\ncancer. <\/p>\n\n\n\n

Table 9: Oxidoreductases target classes used in the present study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Sl. No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

Prostaglandin G\/H synthase 2<\/p>\n<\/td>\n

\n

3LN1<\/p>\n<\/td>\n

\n

587<\/p>\n<\/td>\n

\n

2.40 \u00c5<\/p>\n<\/td>\n

\n

A:-8.5;C:-8.3;Q:-9.8<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

prostaglandin h2 synthase-1<\/p>\n<\/td>\n

\n

1EQH<\/p>\n<\/td>\n

\n

580<\/p>\n<\/td>\n

\n

2.70 \u00c5<\/p>\n<\/td>\n

\n

A:-8.0;C:-8.0;Q:-9.2<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

Corticosteroid 11-beta-dehydrogenase isozyme 1<\/p>\n<\/td>\n

\n

2ILT<\/p>\n<\/td>\n

\n

275<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-8.1;C:-8.6;Q:-8.8<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

Prostaglandin G\/H synthase 2<\/p>\n<\/td>\n

\n

5KIR<\/p>\n<\/td>\n

\n

551<\/p>\n<\/td>\n

\n

2.70 \u00c5<\/p>\n<\/td>\n

\n

A:-8.7;C:-8.4;Q:-9.5<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

myeloperoxidase light chain<\/p>\n<\/td>\n

\n

4C1M<\/p>\n<\/td>\n

\n

108<\/p>\n<\/td>\n

\n

2.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.1;C:-8.1;Q:-9.6<\/p>\n<\/td>\n<\/tr>\n

\n

6.      <\/p>\n<\/td>\n

\n

Cytochrome P450 19A1<\/p>\n<\/td>\n

\n

3S7S<\/p>\n<\/td>\n

\n

503<\/p>\n<\/td>\n

\n

3.21 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4;C:-7.6;Q:-8<\/p>\n<\/td>\n<\/tr>\n

\n

7.      <\/p>\n<\/td>\n

\n

Aldehyde dehydrogenase family 1 member A3<\/p>\n<\/td>\n

\n

6TRY<\/p>\n<\/td>\n

\n

512<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-8.3;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

8.      <\/p>\n<\/td>\n

\n

endothelial Nitric-oxide synthase<\/p>\n<\/td>\n

\n

1M9K<\/p>\n<\/td>\n

\n

415<\/p>\n<\/td>\n

\n

2.01 \u00c5<\/p>\n<\/td>\n

\n

A:-7.5;C:-7.8;Q:-9.5<\/p>\n<\/td>\n<\/tr>\n

\n

9.      <\/p>\n<\/td>\n

\n

Cytochrome P450 2C9<\/p>\n<\/td>\n

\n

1R9O<\/p>\n<\/td>\n

\n

477<\/p>\n<\/td>\n

\n

2.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-7.8;Q:-8.2<\/p>\n<\/td>\n<\/tr>\n

\n

10.   <\/p>\n<\/td>\n

\n

Inducible nitric oxide synthase<\/p>\n<\/td>\n

\n

4NOS<\/p>\n<\/td>\n

\n

427<\/p>\n<\/td>\n

\n

2.25 \u00c5<\/p>\n<\/td>\n

\n

A:-8.5;C:-7.6;Q:-9.3<\/p>\n<\/td>\n<\/tr>\n

\n

11.   <\/p>\n<\/td>\n

\n

Cyclooxygenase-2<\/p>\n<\/td>\n

\n

4COX<\/p>\n<\/td>\n

\n

587<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4;C:-8.6;Q:-9.5<\/p>\n<\/td>\n<\/tr>\n

\n

12.   <\/p>\n<\/td>\n

\n

Cytochrome P450 1A1<\/p>\n<\/td>\n

\n

6DWN<\/p>\n<\/td>\n

\n

491<\/p>\n<\/td>\n

\n

3.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-8.6;Q:-10.5<\/p>\n<\/td>\n<\/tr>\n

\n

13.   <\/p>\n<\/td>\n

\n

Cytochrome P450 1A2<\/p>\n<\/td>\n

\n

2HI4<\/p>\n<\/td>\n

\n

495<\/p>\n<\/td>\n

\n

1.95 \u00c5<\/p>\n<\/td>\n

\n

A:-8.6;C:-9;Q:-9.8<\/p>\n<\/td>\n<\/tr>\n

\n

14.<\/p>\n<\/td>\n

\n

Polyphenol oxidase<\/p>\n<\/td>\n

\n

2Y9X<\/p>\n<\/td>\n

\n

391<\/p>\n<\/td>\n

\n

2.78 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-7.6;Q:-9<\/p>\n<\/td>\n<\/tr>\n

\n

15.<\/p>\n<\/td>\n

\n

Glutathione reductase<\/p>\n<\/td>\n

\n

3DK8<\/p>\n<\/td>\n

\n

478<\/p>\n<\/td>\n

\n

1.10 \u00c5<\/p>\n<\/td>\n

\n

A:-6.9:C:-7.9;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

16.<\/p>\n<\/td>\n

\n

Protein fto<\/p>\n<\/td>\n

\n

3LFM<\/p>\n<\/td>\n

\n

494<\/p>\n<\/td>\n

\n

2.50 \u00c5<\/p>\n<\/td>\n

\n

A:-7.8;C:-7;Q:-7.7<\/p>\n<\/td>\n<\/tr>\n

\n

17.<\/p>\n<\/td>\n

\n

Prostaglandin G\/H synthase 1<\/p>\n<\/td>\n

\n

2OYE<\/p>\n<\/td>\n

\n

600<\/p>\n<\/td>\n

\n

2.85 \u00c5<\/p>\n<\/td>\n

\n

A:-8;C:-8.1;Q:-9.1<\/p>\n<\/td>\n<\/tr>\n

\n

18.   <\/p>\n<\/td>\n

\n

Cytochrome P450 19A1<\/p>\n<\/td>\n

\n

3EQM<\/p>\n<\/td>\n

\n

503<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-7.7;Q:-8<\/p>\n<\/td>\n<\/tr>\n

\n

19.<\/p>\n<\/td>\n

\n

Cytochrome P450 21-hydroxylase<\/p>\n<\/td>\n

\n

4Y8W<\/p>\n<\/td>\n

\n

482<\/p>\n<\/td>\n

\n

2.64 \u00c5<\/p>\n<\/td>\n

\n

A:-8;C:-7.9;Q:-8.7<\/p>\n<\/td>\n<\/tr>\n

\n

20.   <\/p>\n<\/td>\n

\n

Aldehyde dehydrogenase family 1 member A3<\/p>\n<\/td>\n

\n

6TE5<\/p>\n<\/td>\n

\n

512<\/p>\n<\/td>\n

\n

3.25 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-8.3;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

21.   <\/p>\n<\/td>\n

\n

Aldehyde dehydrogenase family 1 member A3<\/p>\n<\/td>\n

\n

7A6Q<\/p>\n<\/td>\n

\n

512<\/p>\n<\/td>\n

\n

2.95 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-8.1;Q:-9<\/p>\n<\/td>\n<\/tr>\n

\n

22.   <\/p>\n<\/td>\n

\n

Prostaglandin h2 synthase-1<\/p>\n<\/td>\n

\n

1EQG<\/p>\n<\/td>\n

\n

580<\/p>\n<\/td>\n

\n

2.61 \u00c5<\/p>\n<\/td>\n

\n

A:-7.6;C:-8;Q:-9.2<\/p>\n<\/td>\n<\/tr>\n

\n

23.   <\/p>\n<\/td>\n

\n

Aldehyde dehydrogenase family 1 member A3<\/p>\n<\/td>\n

\n

5FHZ<\/p>\n<\/td>\n

\n

529<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-8.4;Q:-9.1<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 10: Contact amino acids and varieties of bonds between the target and the ligand molecules belong to oxidoreductases involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues, bond pattern and number of bonds<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1EQH<\/p>\n<\/td>\n

\n

PHE142SER143VAL145
ARG374ASN375ARG376
PHE142SER143VAL145
LEU224GLY225HIS226
ARG374ASN375ARG376<\/p>\n

Hydrogen (3),
hydrophobic (5)<\/p>\n

<\/p>\n<\/td>\n

\n

PHE142SER143VAL
145GLY225HIS226
GLY227VAL228TYR
373ARG374ASN375
ARG376GLY533GLY
536ASN537PRO538
TRP139PHE142VAL
145LEU224GLY225
HIS226ARG374<\/p>\n

Hydrogen (7),
weak hydrogen (2),
hydrophobic (7)<\/p>\n<\/td>\n

\n

ALA199ALA202
GLN203THR206
HIS207PHE210T
HR212LEU295A
SN382TYR385H
IS386TRP387HI
S388LEU390ME
T391ILE444<\/p>\n

Hydrogen (7),
weak hydrogen (3),
hydrophobic (10),
cation pi (1) pi-pi (2)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

2ILT<\/p>\n<\/td>\n

\n

THR40GLY41ALA
42LYS44GLY45ILE4
6GLY47ARG48ASN119
HIS120ILE121VAL168
SER169SER170TYR183
LYS187LEU215GLY216
LEU217ILE218
THR220ALA223<\/p>\n

Hydrogen (6),
Hydrophobic (8),
weak hydrogen (2)<\/p>\n<\/td>\n

\n

GLY41ALA42LYS
44GLY45ILE46GLY
47ARG48ASN119
HIS120ILE121VAL
168SER169SER170
LEU171ALA172TYR
177TYR183LEU215
GLY216LEU217ILE
218THR220THR
222ALA223<\/p>\n

Hydrogen(11),
Hydrophobic (10),
weak hydrogen (4)<\/p>\n<\/td>\n

\n

THR40GLY41AL
A42LYS44GLY4
5ILE46GLY47A
RG48ASN119HI
S120ILE121VAL
168SER169SER
170TYR183LYS
187LEU215GLY
216LEU217ILE
218THR220<\/p>\n

ALA223<\/p>\n

Hydrogen (12),
Hydrophobic (4),
weak hydrogen (5)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3lN1<\/p>\n<\/td>\n

\n

HIS75ARG106GLN
178TYR334VAL335
LEU338SER339TYR
341LEU345LEU370
TYR371TRP373ARG
499ALA502ILE503PHE
504MET508VAL509GLU
510GLY512ALA513SER
516LEU517<\/p>\n

Hydrophobic (8),
weak hydrogen (1),
hydrogen (6)<\/p>\n<\/td>\n

\n

ASN19CYS21CYS
22ASN24PRO25
CYS26ARG29GLY
30GLU31CYS32TYR
120GLY121TYR122
LEU138PRO139PRO
140VAL141ALA142
CYS145GLN447GLU
451LYS454ARG455
GLN313<\/p>\n

Hydrophobic (11),
weak hydrogen (4),
hydrogen (9)<\/p>\n<\/td>\n

\n

ASN19CYS21
CYS22ASN24
CYS26GLN27
ARG29GLY30
GLU31CYS32
MET33TYR116
GLY121LEU138
PRO139PRO140
VAL141ALA142
GLN447GLU451
LYS454ARG455<\/p>\n

Ionic (4),
Hydrophobic (6),
weak hydrogen (4),
hydrogen (19)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

4C1M<\/p>\n<\/td>\n

\n

ALA28PHE29VAL
30ARG31PRO34
ALA35ARG31
ALA152THR159
ILE160ARG161A
SN162ARG323
THR159ILE160ARG323<\/p>\n

Hydrophobic (8),
hydrogen bonds (3)<\/p>\n

<\/p>\n<\/td>\n

\n

MET87GLY90GLN91
ASP94HIS95GLU102
PHE146PHE147ARG
239TYR296PHE332
ARG333TYR334GLY
335HIS336LEU406
PHE407LEU415LEU
417LEU420ARG424<\/p>\n

Hydrophobic (7),
weak hydrogen (2),
ionic (2)hydrogen (6),
cation pi (2)<\/p>\n<\/td>\n

\n

PHE86MET87GL
Y90GLN91ASP9
4HIS95ASP98P
HE99THR100<\/p>\n

ARG239GLU242
TYR296THR329
ASN330PHE332
ARG333TYR334
GLY335HIS336L
EU338<\/p>\n

Cation-pi (1),
weak hydrogen (2),
Hydrophobic (8),
hydrogen (8), ionic (1),
pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

5KIR<\/p>\n<\/td>\n

\n

CYS36HIS39PRO40 CYS41<\/p>\n

GLN42ASN43ARG
44GLY45VAL46CYS
47TYR130LYS137ALA
151LEU152PRO153G
LN461GLU465LYS468<\/p>\n

ARG469<\/p>\n

Hydrophobi (10),
hydrogen (5),
weak hydrogen (2),
ionic (2)<\/p>\n

<\/p>\n<\/td>\n

\n

TRP323GLN327ASN
34CYS36HIS39PRO40
CYS41GLN42ARG44
GLY45VAL46CYS47
MET48SER49TYR130
GLY135TYR136LEU
152PRO153PRO154
VAL155PRO156GL
N461GLU465<\/p>\n

Hydrophobic (9),
hydrogen (8),
weak hydrogen (4),
ionic (1)<\/p>\n<\/td>\n

\n

ASN34CYS36HIS
39CYS41ARG44G
LY45VAL46CYS4
7MET48TYR130
GLY135TYR136
LEU152PRO153
PRO154VAL155
PRO156GLN461
GLU465<\/p>\n

Hydrophobic (5),
hydrogen (10),
weak hydrogen (1),
ionic (1)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

1EQG<\/p>\n<\/td>\n

\n

PHE142SER143
VAL145LEU224
GLY225HIS226
ARG374ASN375
ARG376Chain
B:PHE142SER143
VAL145ARG374
ASN375ARG376<\/p>\n

Hydrogen (4),
hydrophobic (4)<\/p>\n

<\/p>\n<\/td>\n

\n

PHE142SER143VAL
145GLY225HIS226
GLY227VAL228TYR
373ARG374ASN375
ARG376GLY533GLY
536ASN537PRO538
TRP139PHE142SER
143VAL145LEU224
GLY225HIS226ARG
374ASN375ARG376<\/p>\n

Hydrogen (9),
hydrophobic (9),
cation pi (1),
weak hydrogen (2)<\/p>\n<\/td>\n

\n

ALA199PHE200
ALA202GLN203
THR206HIS207
PHE210THR212
LEU295ASN382
TYR385HIS386
TRP387HIS388L
EU390MET391I
LE444VAL447<\/p>\n

Hydrogen (11),
hydrophobic (6)
pi-pi (1), weak
hydrogen (1)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3S7S<\/p>\n<\/td>\n

\n

ARG115ILE132
ILE133TRP<\/p>\n

141ARG145PHE
148LEU152TRP
224GLU302MET
303ILE305ALA
306ASP309THR
310ARG435GLY
436CYS437ALA438<\/p>\n

GLY439<\/p>\n

Cation pi (1),
hydrophobic (18),
hydrogen (8)<\/p>\n<\/td>\n

\n

ARG115ILE132ILE
133PHE134PHE148
LEU152TRP224GLU
302MET303ALA306
VAL370LEU372VAL
373MET374PHE430
ARG435GLY436CYS
437ALA438GLY439
LEU477<\/p>\n

Hydrophobic (18),
weak hydrogen (2)
hydrogen (11)<\/p>\n<\/td>\n

\n

ARG115ILE132IL
E133TRP141ARG
145LEU152PHE203
MET303ALA306AL
A307THR310MET3
11VAL370ARG435
GLY436CYS437AL
A438GLY439ILE4
42ALA443 MET446<\/p>\n

Cation pi (1),
hydrophobic (6),
weak hydrogen
(3)hydrogen bonds (13)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

1R9O<\/p>\n<\/td>\n

\n

ARG97ILE112
VAL113PHE114
TRP120ALA297
THR301LEU362
SER365LEU366
HIS368PHE428
SER429ARG433ILE
434CYS435VAL436<\/p>\n

Pi-pi stacking (1)
Hydrophobic (18)<\/p>\n

<\/p>\n<\/td>\n

\n

ARG97ILE112VAL
113ARG124ILE205
GLY296ALA297GL
U300THR301THR
304LEU361LEU362
LEU366PHE428AR
G433ILE434CYS43
5VAL436GLY437<\/p>\n

ALA477<\/p>\n

Hydrophobic (12),
weak hydrogen (3),
hydrogen (9)<\/p>\n<\/td>\n

\n

ARG97VAL113A
LA297GLY298T
HR301THR302T
HR305GLN356L
EU361LEU362S
ER365LEU366H
IS368LEU391PR
O427PHE428SER
429ARG433CYS4
35ALA441LEU445<\/p>\n

Hydrophobic (8),
weak hydrogen (4),
hydrogen (14)<\/p>\n<\/td>\n<\/tr>\n

\n

6TE5<\/p>\n<\/td>\n

\n

ARG276ASN485
GLY486ARG487
TYR492ALA495
GLU496HIS168
ILE171ARG276
THR278ASN485
GLY486LEU494
ALA495GLU496
TYR497THR498
GLU499VAL500<\/p>\n

Hydrogen (9),
ionic (6), hydrophobic
(4), weak hydrogen (4)<\/p>\n<\/td>\n

\n

LYS266ARG276VAL
277THR278ASN485
GLY486ALA495GLU
496THR498GLU499
VAL500LYS266LYS
275ARG276VAL277
THR278ASN485GLY
486ARG487TYR492
ALA495GLU496<\/p>\n

Weak hydrogen (7),
hydrogen (14), ionic (3),
hydrophobic (10)<\/span><\/p>\n<\/td>\n

\n

LYS266VAL277
THR278GLY479
ASN485GLY486
ARG487GLU496
LYS266LYS275A
RG276VAL277T
HR278ASN485L
EU494ALA495G
LU496THR498
GLU499 VAL500<\/p>\n

Hydrophobic (6),
ionic (2), weak
hydrogen (5),
hydrogen (17)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

2Y9X<\/p>\n<\/td>\n

\n

PHE97TYR101ALA
104PHE105LEU108
VAL126GLU129LEU
130GLY138ARG139
ALA142PHE143SER
145 PHE146<\/p>\n

Hydrophobic (8),
weak hydrogen (3),
hydrogen (6), ionic (3)<\/p>\n

<\/p>\n<\/td>\n

\n

GLN307THR308TYR
311ASP312VAL313S
ER352ASP353ASP354
GLU356ASP357TRP
358SER375LYS376
LYS379SER380ASP
336GLN351ASP353
ASP354GLU356<\/p>\n

Hydrophobic (8),
weak hydrogen (1),
hydrogen (7), ionic (2)<\/p>\n<\/td>\n

\n

SER2ASP3LYS5ASP
336SER337PRO338
TYR343ASN346GLN
347ASP348PRO349
GLN351TYR311ASP
312SER375LYS376
GLU377GLU378AS
N57LEU59ASP60GL
Y61TYR62<\/p>\n

Hydrophobic (2),
weak hydrogen (7),
ionic (1)hydrogen (13)<\/p>\n<\/td>\n<\/tr>\n

\n

6TRY<\/p>\n<\/td>\n

\n

PRO179TRP180ASN
181GLN208PHE255
GLY257SER258VAL
261GLY282GLN312
CYS313CYS314ILE
357ASP358LYS360
GLN361LYS364
GLU411PHE413<\/p>\n

Hydrophobic (7),
ionic (4),
hydrogen (1)<\/p>\n

<\/p>\n<\/td>\n

\n

LYS266ARG276
VAL277ASN485GLY
486ARG487TYR492
ALA495GLU496
ChainB:LYS25LYS
266LYS275ARG276
VAL277THR278ASN
485GLY486ALA495G
LU496THR498GLU499
VAL500<\/p>\n

Hydrophobic (8),
weak hydrogen (4),
ionic (2), hydrogen (8)<\/p>\n<\/td>\n

\n

HIS168ARG276L
EU494ALA495G
LU496THR498G
LU499VAL500
ChainB:GLY479
ASN485GLY486
ARG487GLU491
TYR492ALA493L
EU494 ALA495G
LU496<\/p>\n

Pi-pi stacking (1),
hydrophobic (3),
weak hydrogen (3), 
hydrogen (15), ionic (2)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3EQM<\/p>\n<\/td>\n

\n

ARG115ILE132I
LE133TRP141ARG
145PHE148LEU152
TRP224GLU302MET
303ILE305ALA306
ASP309THR310ARG
435GLY436CYS437
ALA438GLY439<\/p>\n

Cation pi (1), hydrogen
(9), hydrophobic (16)<\/p>\n<\/td>\n

\n

ARG115ILE132IL
E133PHE134ARG
145PHE148LEU152
TRP224GLU302MET
303ALA306VAL370
LEU372VAL373MET
374PHE430GLY436
CYS437ALA438GLY
439LEU477<\/p>\n

Hydrogen (15),
weak hydrogen (2),
hydrophobic (18)<\/p>\n<\/td>\n

\n

ARG192GLN218
PHE221ASP222
GLN225PRO308
ASP309THR310
VAL313ILE474S
ER478HIS480ASP
482GLU483THR484<\/p>\n

Pi-pi (2), cation pi (1),
hydrogen (7,weak
hydrogen (3),
hydrophobic
(6), ionic (1)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3lFM<\/p>\n<\/td>\n

\n

ILE85THR92PRO93
VAL94ARG96TYR106
TYR108LEU109LEU203
ALA227VAL228SER229
TRP230HIS231HIS232ASP233<\/p>\n

GLU234ARG322<\/p>\n

Pi-pi stacking (2),
hydrophobic (9),
weak hydrogen (3),
<\/span>hydrogen (2), ionic (5)<\/p>\n<\/td>\n

\n

ILE85THR92PRO93
VAL94ARG96TYR106
TYR108LEU109LEU
203ALA227VAL228
SER229HIS231HIS
232ASP233GLU234
ARG322<\/p>\n

Pi-pi stacking (2),
hydrophobic (5),
weak hydrogen (2),
hydrogen (8), ionic (3)<\/p>\n<\/td>\n

\n

ILE85ARG96TYR
106TYR108LEU1
09LEU203ASN20
5VAL228SER229
TRP230HIS231H
IS232ASP233GL
U234THR320AR
G322<\/p>\n

Cation-pi (1),
pi-pi stacking (2),
hydrophobic (5),
weak hydrogen (4),
hydrogen (9), ionic (2)<\/p>\n<\/td>\n<\/tr>\n

\n

4COX<\/p>\n<\/td>\n

\n

CYS36ASN39PRO
40CYS41GLN42ASN
43ARG44GLY45GLU
46CYS47ASP125TYR
130ALA151LEU152
PRO153GLN461GLU
465LYS468ARG469<\/p>\n

Ionic (3), hydrophobic
(5), weak hydrogen
(2), hydrogen (4)<\/p>\n

<\/p>\n<\/td>\n

\n

ASN34CYS36CYS37
SER38ASN39CYS47
MET48SER49TYR130
GLY135TYR136LYS
137SER138PRO153
PRO154VAL155ALA
156CYS159GLY164
GLN461TRP323GLN
327THR331LEU334
SER548THR549 GLY551<\/p>\n

Hydrophobic(6),
weak hydrogen (2),
ionic (1) hydrogen (7)<\/p>\n<\/td>\n

\n

ASN34CYS36CYS
37SER38ASN39C
YS41GLN42ARG
44GLY45GLU46
CYS47MET48TYR
130GLY135PRO
153PRO154VAL
155ALA156CYS
159 GLY164GLN461<\/p>\n

Hydrophobic (9),
weak hydrogen (5),
pi-pi (2), cation pi (1),
hydrogen  (11)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

1M9K<\/p>\n<\/td>\n

\n

GLN90GLY92PRO
93ALA181PRO182
ARG183CYS184MET
339ASP444TRP447
ASN466TYR467
PHE468ALA472
PHE473ARG474TYR475<\/p>\n

Hydrophobic (8),
ionic (2), cation pi (1),
hydrogen (2)<\/p>\n

<\/p>\n<\/td>\n

\n

TRP74TRP445PHE
460HIS461GLN462
ChainB:SER102VAL
104GLN247ARG250
ALA266ARG365ASN
366ASP369HIS371AR
G372ALA446TRP447<\/p>\n

Hydrophobic (9),
ionic (1), hydrogen (4),
weak hydrogen (3)<\/p>\n<\/td>\n

\n

VAL71LYS72ASN
73VAL76SER78I
LE79THR80ASP
82MET428LYS4
29LEU431GLU4
32GLU434GLN4
35GY439GLY440
CYS441PRO442G
LN62GLU463ME
T464VAL465<\/p>\n

Hydrophobic (11),
ionic (1), hydrogen
(14), weak hydrogen (5)<\/p>\n<\/td>\n<\/tr>\n

\n

2HI4<\/p>\n<\/td>\n

\n

ARG108LEU123THR
124PHE125TRP133
ARG137ALA317THR
321LEU382PHE384
THR385ILE386HIS388
GLN411LEU450PHE451
GLY452ARG456ARG457<\/p>\n

CYS458ILE459LEU497<\/p>\n

Cation-pi (1),
hydrophobic (13),
weak hydrogen (1),
hydrogen (9)<\/p>\n<\/td>\n

\n

ARG108THR124PHE
125THR223PHE226
VAL227PHE256PHE
260GLY316ALA317
ASP320THR321LEU
382PHE384THR385I
LE386HIS388GLN411
LEU450PHE451GLY45
2ARG456ARG457CYS4
58ILE459LEU497THR498<\/p>\n

Hydrophobic (19),
weak hydrogen (4),
hydrogen (9)<\/p>\n<\/td>\n

\n

ARG108ILE117T
HR118SER122T
HR124PHE125T
HR223PHE226V
AL227PHE256P
HE260ASN312A
SP313GLY316AL
A317ASP320TH
R321LEU382ILE
386LEU497THR498<\/p>\n

Hydrophobic (18),
weak hydrogen (1), 
hydrogen (8), pi-pi (1)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

4NOS<\/p>\n<\/td>\n

\n

TRP90TRP461PHE476
HIS477ChainD:SER118
ILE119MET120ARG199
ARG381ASP385ARG388
ILE462TRP463VAL465<\/p>\n

PRO467<\/p>\n

Pi-pi stacking (1),
cation-pi (2),
hydrophobic (9),
weak hydrogen (3),
ionic (2),
<\/span>hydrogen (5)<\/p>\n<\/td>\n

\n

LEU125ALA197
PRO198ARG199
CYS200ILE201
GLY202MET355
PHE369TRP372
TYR373MET374
GLU377TRP463
PHE488TYR489
TYR490TYR491<\/p>\n

Pi-pi (2), cation pi(1),
hydrophobic (7),
weak hydrogen (1),
hydrogen (5)<\/p>\n<\/td>\n

\n

GLY117SER118
MET120ARG381I
LE462TRP463VAL
465ChainB:LYS88
TRP90TRP461VAL
475PHE476HIS477
GLN478GLU479<\/p>\n

MET480<\/p>\n

Pi-pi stacking (3),
cation-pi (1),
hydrophobic (6),<\/p>\n

weak hydrogen (5),
hydrogen (8)<\/p>\n<\/td>\n<\/tr>\n

\n

3DK8<\/p>\n<\/td>\n

\n

CYS58CYS63VAL
64LYS66LYS67TYR
197LEU337LEU338
THR339PRO340PRO
368THR369VAL370
PHE372ASP441LEU444<\/p>\n

GLN445<\/p>\n

Hydrophobic (1),
hydrogen (7),
ionic (3)<\/span><\/p>\n

<\/p>\n<\/td>\n

\n

GLY27GLY28GLY
29SER30GLY31G
LU50SER51HIS
52LYS53GLY5
5GLY56THR57
CYS58CYS63A
LA155THR156
GLY157GLY15
8TYR197ARG2
91ASN294ASP
331LEU337
LEU338THR339<\/p>\n

ALA342<\/p>\n

Hydrophobic (5),
weak hydrogen (4), 
hydrogen (8) ionic (2)<\/p>\n<\/td>\n

\n

GLY27GLY28
GLY29SER30GL
Y31GLY32GLU5
0SER51HIS52GL
Y55GLY56THR57
CYS58VAL61CYS
63ALA155THR15
6GLY157GLY158
GLY330ASP331L
EU337LEU338TH
R339ALA342<\/p>\n

Hydrophobic (2),
weak hydrogen (4), 
hydrogen (13), ionic (1)<\/p>\n<\/td>\n<\/tr>\n

\n

2OYE<\/p>\n<\/td>\n

\n

CYS36TYR39PRO40
CYS41GLN44GLY45
ILE46CYS47THR129
TYR130ASP135ILE15
1LEU152PRO153GL
N461GLU465<\/p>\n

ARG469<\/p>\n

Ionic (1),
weak hydrogen (1),
hydrogen (2),
Hydrophobic (9)<\/p>\n

<\/p>\n<\/td>\n

\n

ASN34CYS36TYR39
PRO40CYS41GLN42
HIS43GLN44GLY45
ILE46CYS47VAL48
TYR130ASP135TYR
136LEU152PRO153
SER154PRO156GLN
461GLU465LYS468
ARG469<\/p>\n

Ionic (1), weak hydrogen (5), hydrogen (7), Hydrophobic (7)<\/p>\n<\/td>\n

\n

ALA199PHE200A
LA202GLN203THR
206HIS207PHE210L
YS211THR212ASN
382TYR385HIS
386TRP387HI
S388LEU390ME
T391VAL447<\/p>\n

Weak hydrogen
(3), hydrogen (9),
Hydrophobic (8),<\/p>\n

pi-pi (1), cation-pi (1)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 8: Docking poses of oxidoreductases with Anastrazole, Capecitabine and Quercetin ligands<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Proteins as targets<\/strong><\/p>\n\n\n\n

Table\n11 provides the vina score comparison; wherein, quercetin showed the highest\nvina score for protein binding targets and table 12 shows the contact residues\nand bonds (Tables 11, 12) (Fig. 9)20<\/sup>. Overexpressed HSP90 aids\ntransformation by stabilizing the mutated and overexpressed onco-proteins\nidentifed in BC cells. Carcinoma-associated\nantigen is the epithelial cell adhesion\nmolecule (EpCAM).\nHER 2, a member of an oncogenic protein family, involves in development and\nprogression of breast cancers that are aggressive. Methenyltetrahydrofolate\nSynthetase regulates carbon flow by one-carbon metabolic network, which\nprovides vital constituents for cell growth and proliferation; reserve has been\nshown to arrest the cell growth. ALDH1A3 is overexpressed\nand important for tumor cell\u2019s vitality. HER 2 stimulates\ncell propagation in tissues. ER binds to either of structurally and\nfunctionally distinct ERs (ER\u03b1<\/em> and ER\u03b2<\/em>). PKC delta\u2019s C2 domain is activated by diacylglycerol, and functions as a tumor suppressor, a\nregulator of cell cycle progression (positive) and a regulator of apoptosis\n(positive or negative). Estrogen Receptor alpha LBD, (a novel isoform\nof ER\u03b1), promotes endocrine resistance\nand cancer proliferation (breast). Ephrin type-A receptor 2 (EphA2) (a\nreceptor tyrosine kinase), overexpresses in breast cancers (human) and involves\nin a variety of serious progressions related to malignant breast progressions,\nincluding proliferation, migration, survival, invasion, metastasis, drug\nresistance, and angiogenesis20<\/sup>.<\/p>\n\n\n\n

Table 11: Protein binding target classes used in the present study EphA2: ephrin type-A receptor 2<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Sl. No.<\/strong><\/p>\n<\/td>\n

\n

Protein Molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

Estrogen receptor<\/p>\n<\/td>\n

\n

4PPS<\/p>\n<\/td>\n

\n

244<\/p>\n<\/td>\n

\n

1.93 \u00c5<\/p>\n<\/td>\n

\n

A:-7.2;C:-7.5;Q:-7.7<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

Estrogen receptor<\/p>\n<\/td>\n

\n

4PP6<\/p>\n<\/td>\n

\n

244<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-7.3;C:-7.2;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

Protein kinase C, delta type<\/p>\n<\/td>\n

\n

1YRK<\/p>\n<\/td>\n

\n

126<\/p>\n<\/td>\n

\n

1.70 \u00c5<\/p>\n<\/td>\n

\n

A:-6.3;C:-6.4;Q:-7.1<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

Estrogen receptor beta<\/p>\n<\/td>\n

\n

4J26<\/p>\n<\/td>\n

\n

240<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-6.9;C:-7.4;Q:7.7<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

estrogen receptor alpha (hER alpha)<\/p>\n

(protein (estrogen receptor alpha)<\/p>\n<\/td>\n

\n

3ERT<\/p>\n<\/td>\n

\n

261<\/p>\n<\/td>\n

\n

1.90 \u00c5<\/p>\n<\/td>\n

\n

A:-8.1;C:-7.5;Q:-7.8<\/p>\n<\/td>\n<\/tr>\n

\n

6.      <\/p>\n<\/td>\n

\n

EphA2 ectodomain<\/p>\n<\/td>\n

\n

2X10<\/p>\n<\/td>\n

\n

545<\/p>\n<\/td>\n

\n

3.00 \u00c5<\/p>\n<\/td>\n

\n

A:-6.5;C:-5.8;Q:-6.5<\/p>\n<\/td>\n<\/tr>\n

\n

7.      <\/p>\n<\/td>\n

\n

Stress-70 protein, mitochondrial<\/p>\n<\/td>\n

\n

3N8E<\/p>\n<\/td>\n

\n

182<\/p>\n<\/td>\n

\n

2.80 \u00c5<\/p>\n<\/td>\n

\n

A:-7.4;C:-7.6;Q:-7.7<\/p>\n<\/td>\n<\/tr>\n

\n

8.      <\/p>\n<\/td>\n

\n

Aldehyde dehydrogenase family 1 member A3<\/p>\n<\/td>\n

\n

6S6W<\/p>\n<\/td>\n

\n

489<\/p>\n<\/td>\n

\n

3.25 \u00c5<\/p>\n<\/td>\n

\n

A:-8.1;C: -8.5; Q:-9.0<\/p>\n<\/td>\n<\/tr>\n

\n

9.      <\/p>\n<\/td>\n

\n

5,10-Methenyltetrahydrofolate cyclo-ligase<\/p>\n<\/td>\n

\n

3HY3<\/p>\n<\/td>\n

\n

203<\/p>\n<\/td>\n

\n

1.80 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4; C:-7.4; Que:-8.2<\/p>\n<\/td>\n<\/tr>\n

\n

10.   <\/p>\n<\/td>\n

\n

Met and epithelial cell adhesion molecule<\/p>\n<\/td>\n

\n

6I07<\/p>\n<\/td>\n

\n

262<\/p>\n<\/td>\n

\n

2.35 \u00c5<\/p>\n<\/td>\n

\n

A:-6.8; C:-6.9;Q:-7.2<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 12: Contact amino acids and varieties of bonds between the target and the ligand molecules belong to binding proteins involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues, bond pattern and number of bonds<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

6S6W<\/p>\n<\/td>\n

\n

PRO179TRP180
ASN181GLY257
SER258THR259
GLU260LEU281
GLY282GLY283
CYS313CYS314A
LA316GLN361G
LU411PHE413<\/p>\n

Ionic (2), pi-pi, (1)
hydrogen (5),
hydrophobic (4),
cation-pi (1)<\/p>\n<\/td>\n

\n

LYS266ARG276
VAL277ASN485
GLY486ARG487
TYR492ALA495
GLU496Chain
B:LYS266LYS275
ARG276VAL277
THR278ASN485
ALA495GLU496
THR498GLU499
VAL500<\/p>\n

Ionic (4), hydrogen
(12), hydrophobic (7),
cation-pi (1), weak
hydrogen (6)<\/p>\n<\/td>\n

\n

LYS266LYS275
ARG276VAL277
ASN485ALA495
GLU496THR498
GLU499VAL500
ChainB:LYS266LY
S275ARG276VAL277
ASN485GLY486ARG
487TYR492ALA495
GLU496<\/p>\n

Ionic (4), hydrogen (14),
hydrophobic (3),
weak hydrogen (4)<\/p>\n<\/td>\n<\/tr>\n

\n

4PPS<\/p>\n<\/td>\n

\n

MET343LEU346
THR347LEU349
ALA350GLU353
TRP383LEU384L
EU387MET388LE
U391ARG394PHE
404MET421ILE424
PHE425LEU428GLY
521HIS524LEU525<\/p>\n

Ionic (2), weak hydrogen
(2), hydrogen (3),
hydrophobic (23), pi-pi (1)<\/p>\n<\/td>\n

\n

GLU323PRO324PRO
325ILE326GLU353
HIS356MET357TRP
360ILE386LEU387
GLY390TRP393AR
G394GLY442PHE4
45VAL446LYS449<\/p>\n

Hydrogen (2),
hydrophobic (18),
weak  hydrogen (1),
cation-pi (1), ioninc
(2), pi-pi (1)<\/p>\n<\/td>\n

\n

MET343LEU346
THR347LEU349
ALA350ASP351
GLU353LEU384
LEU387MET388
GLY390LEU391
ARG394PHE404
VAL418MET421I
LE424LEU428GL
Y521MET522HIS
524LEU525TY
R526MET528<\/p>\n

Hydrophobic (13),
hydrogen 2 (4),
pi-pi (1), ionic (1)<\/p>\n<\/td>\n<\/tr>\n

\n

4PP6<\/p>\n<\/td>\n

\n

MET343LEU346
THR347LEU349
ALA350GLU353
TRP383LEU384
LEU387MET388
LEU391ARG394
PHE404MET421
ILE424PHE425
LEU428GLY521
MET522LEU525
LEU540<\/p>\n

Hydrophobic (26),
hydrogen (1), ionic
(3), weak hydrogen (2)<\/p>\n

<\/p>\n<\/td>\n

\n

GLU323PRO324
PRO325ILE326
GLU353HIS356
MET357TRP360I
LE386LEU387GL
Y390TRP393ARG
394GLY442PHE44
5VAL446 LYS449<\/p>\n

Hydrophobic (16),
pi-pi (1), ionic (2),
cation-pi (2), hydrogen (1)<\/p>\n

<\/p>\n<\/td>\n

\n

MET343LEU346
THR347LEU349
ALA350GLU353
LEU384LEU387
MET388ILE389
LEU391ARG394
PHE404VAL418
MET421ILE424
LEU428LYS520
GLY521MET52
2HIS524LEU525
MET528<\/p>\n

Hydrogen (7), ionic
(1), pi-pi (2), hydrophobic
(11), weak hydrogen (1)<\/p>\n<\/td>\n<\/tr>\n

\n

1YRK<\/p>\n<\/td>\n

\n

MET32GLU34
LYS47LYS48PR
O49ASP60HIS6
2TYR64<\/p>\n

ARG67GLN8
PRO9TYR10<\/p>\n

PHE12<\/p>\n

Hydrogen (2),
hydrophobic (6),<\/p>\n

pi-pi (2)<\/p>\n<\/td>\n

\n

THR50MET51
TYR52PRO53G
LU54LYS56SER
57THR58PHE59
ChainB:GLN8PRO9
TYR10VAL11
PHE12ALA13<\/p>\n

Hydrogen (8),
hydrophobic (5),<\/p>\n

ionic (1),
cation-pi (1)<\/p>\n<\/td>\n

\n

PHE4LYS48PRO49ASP60
ALA61HIS62TYR64ARG
67GLU123ChainB:ILE
6GLN8PRO9TYR10PHE12<\/p>\n

Hydrogen (7),
hydrophobic (5),
ionic (1) pi-pi (2),
cation-pi (1) weak
hydrogen (1)<\/p>\n<\/td>\n<\/tr>\n

\n

3ERT<\/p>\n<\/td>\n

\n

MET343LEU346
THR347ALA350
ASP351LEU354
TRP383LEU384
LEU387MET522
LEU525MET528L
EU536LEU539<\/p>\n

Hdrogen (3),
hydrophobic (12)<\/p>\n

<\/p>\n<\/td>\n

\n

LEU320GLU323
PRO324PRO325
ILE326LEU327
GLU353LEU354
HIS356MET357
TRP360ILE386
LEU387GLY390
TRP393ARG394
GLY442PHE445
VAL446LYS449<\/p>\n

Hydrogen (4),
hydrophobic (16),
ionic (1),<\/p>\n<\/td>\n

\n

MET343LEU346THR
347LEU349ALA350A
SP351GLU353TRP383
LEU384LEU387MET
388LEU391ARG394
PHE404ILE424LEU428
GLY521<\/p>\n

LEU525MET528<\/p>\n

Hydrogen (5), ionic (1),
hydrophobic (13),<\/p>\n<\/td>\n<\/tr>\n

\n

2X10<\/p>\n<\/td>\n

\n

GLN56
ASN57ILE64TYR
65TYR67SER68
VAL69
THR101ARG
103CYS188VAL
189ALA190LEU
191LEU192<\/p>\n

Hydrophobic (5),
hydrogen (2),
weak hydrogen (3)<\/p>\n<\/td>\n

\n

VAL364THR365CYS366
GLU367PRO378CYS379
GLU380ALA381VAL383
ARG384TYR385 PRO389
HIS390<\/p>\n

Weak hydrogen (3),
Hydrophobic (13)<\/p>\n<\/td>\n

\n

THR365CYS366PRO
378 CYS379GLU380
ALA381SER382VAL
383TYR385PRO389<\/p>\n

HIS390<\/p>\n

Hydrophobic (7),
hydrogen (3), weak
hydrogen (4)<\/p>\n<\/td>\n<\/tr>\n

\n

3N8E<\/p>\n<\/td>\n

\n

ILE447GLU448
THR449LEU450
PHE472SER473
THR474ALA475
GLN479GLN481
VAL482GLU483I
LE484ARG513<\/p>\n

ILE518VAL520<\/p>\n

Hydrophobic (14),
hydrogen (2)<\/p>\n

<\/p>\n<\/td>\n

\n

ILE447GLU448THR
449LEU450PHE472
SER473THR474ALA
475VAL482GLU483I
LE484ARG513ILE518
VAL520ASN583MET58
4GLU586<\/p>\n

GLY587<\/p>\n

Hydrophobic (14),
hydrogen (5), weak
hydrogen (1), ionic (1)<\/p>\n<\/td>\n

\n

ILE447GLU448THR
449LEU450PHE472
SER473THR474ALA
475GLN479VAL482
GLU483ILE484ARG
513ILE518 VAL520<\/p>\n

Hydrophobic (13),
hydrogen (7),
weak hydrogen (1)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

3HY3<\/p>\n<\/td>\n

\n

ILE54PHE55LEU
56MET58GLU61
ILE80PRO81ARG
82TYR83PHE85
THR107TRP109
ILE111PRO112G
LN113PRO135ARG
148TYR152TYR153<\/p>\n

Pi-pi (2), weak hydrogen (1),
hydrogen (2), hydrophobic (6)<\/p>\n<\/td>\n

\n

LEU56MET58PRO
81ARG82TYR83P
HE85THR107TRP
109ILE111PRO112
GLN113GLY147AR
G148GLY149<\/p>\n

LYS150GLY151TYR152<\/p>\n

Pi-pi (2), hydrogen (4),
weak hydrogen (1),
hydrophobic (9)<\/p>\n<\/td>\n

\n

PHE55 LEU56 SER57
MET58GLU61ILE80P
RO81ARG82TYR83P
HE85THR107TRP10
9ILE111PRO112GL
N113PRO135ARG148
LYS150<\/p>\n

TYR152TYR153<\/p>\n

Hydrogen (10), weak
hydrogen (2), ionic (1),
hydrophobic (8), pi-pi (4)<\/p>\n<\/td>\n<\/tr>\n

\n

4J26<\/p>\n<\/td>\n

\n

ARG466HIS467ASN
470LYS471Chain
B:ARG466HIS467
ASN470LYS471
MET473GLU474LEU477
HIS498<\/p>\n

Hydrogen (4), cation-pi
(1), weak hydrogen (1),
hydrophobic (9)<\/p>\n

<\/p>\n<\/td>\n

\n

GLU276PRO277
PRO278HIS279
VAL280LYS304
GLU305LEU306
HIS308MET309
TRP312VAL338L
EU339GLY342TR
P345ARG346ILE
355TYR397LYS401<\/p>\n

Hydrogen (2), cation-pi,
(1) weak hydrogen (3),
hydrophobic (14), pi-pi (1),
ionic (2)<\/p>\n<\/td>\n

\n

MET295LEU298LEU
301ALA302GLU305
TRP335MET336
LEU339MET340LE
U343ARG346PHE35
6ILE373ILE376PHE3
77LEU380GLY472M
ET473HIS475LEU476<\/p>\n

Hydrogen (7),
weak hydrogen (2),
hydrophobic (20),
pi-pi (1), ionic (1)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

6I07<\/p>\n<\/td>\n

\n

ARG125PRO257
PHE259Chain
D:ARG81LEU88
GLN89ASN91
GLN111MET115
TRP117LYS129<\/p>\n

Hydrophobic (4), hydrogen (3), weak hydrogen (2), pi-pi (1)<\/p>\n

<\/p>\n<\/td>\n

\n

GLU217LYS221
GLU223PRO244
GLY245GLN246T
HR247LEU248I
LE249TYR250TY
R251Chain
D:LEU88GLN89
ASN90LYS221GL
U223PRO244GLY245<\/p>\n

Hydrophobic, hydrogen
(10), weak hydrogen
(4), pi-pi (1)<\/p>\n<\/td>\n

\n

ASP1ILE2VAL3MET4T
HR5PRO100ARG101TH
R102PHE103GLY104CY
S105CYS171LEU172LYS
173TRP174MET175ALA
188ASP189ASP190<\/p>\n

Hydrophobic (3), hydrogen (9), weak hydrogen (4)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 9: Docking poses of binding proteins with the three ligands<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Signal\nproteins as targets<\/strong><\/em><\/p>\n\n\n\n

With a minor\ndifference, among the three drugs, quercetin\u2019s vina score is the highest\n(Tables 13, 14) (Fig. 10) for signaling proteins20<\/sup>. EGFR promotes tumorigenesis by regulating epithelial\ntissue development and homeostasis. \u03b2-arrestin regulates cell proliferation,\nmigration, promotes cell invasion, sends anti-apoptotic survival signals,\ninfluences tumor growth rate, metastatic potential, angiogenesis, and drug\nresistance. CXCL12, secreted by carcinoma-associated fibroblasts (CAFs),\ndirectly stimulates tumor growth by acting through CXCR4, which is articulated\nby BC cells and promotes invasiveness. During tumor development, CXCL12 also\nacts as a chemo-attractant. In malignant tumors, its expression promotes\nand contributes for tumor growth and metastasis. CCR5 may indirectly affect\ncancer development by regulating the antitumor immune response20<\/sup>.<\/p>\n\n\n\n

Table 13: Signaling protein target classes used in the present study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n
\n

Sl. No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

Chimera protein of C-C chemokine receptor type 5 and Rubredoxin<\/p>\n<\/td>\n

\n

4MBS<\/p>\n<\/td>\n

\n

414<\/p>\n<\/td>\n

\n

2.71 \u00c5<\/p>\n<\/td>\n

\n

A:-8.6;C:-7.3;Q:-7.9<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

epidermal growth factor<\/p>\n<\/td>\n

\n

1JL9<\/p>\n<\/td>\n

\n

51<\/p>\n<\/td>\n

\n

3.00 \u00c5<\/p>\n<\/td>\n

\n

A:-6.2;C:-6.4;Q:-6.4<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

Beta-arrestin-2<\/p>\n<\/td>\n

\n

6K3F<\/p>\n<\/td>\n

\n

377<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-8.9;C:-8.2Q:-9<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

Stromal cell-derived factor 1<\/p>\n<\/td>\n

\n

2NWG<\/p>\n<\/td>\n

\n

68<\/p>\n<\/td>\n

\n

2.07 \u00c5<\/p>\n<\/td>\n

\n

A:-6.6;C:-5.9;Q:-6.9<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

Receptor tyrosine-protein kinase erbB-2 (HER 2)<\/p>\n<\/td>\n

\n

5O4G<\/p>\n<\/td>\n

\n

606<\/p>\n<\/td>\n

\n

3.00 \u00c5<\/p>\n<\/td>\n

\n

A:7.4;c:8;q:8.4<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 14: Contact amino acids and varieties of bonds between the target and the ligand molecules belong signaling involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues and bond pattern<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

4MBS<\/p>\n<\/td>\n

\n

TYR37TRP86TYR89
LEU104THR105TYR
108PHE109THR167
CYS178SER179SER1
80GLN280GLU283<\/p>\n

THR284 MET287<\/p>\n

Hydrogen (4),
hydrophobic (7),<\/p>\n

ionic (2), weak hydrogen
(2), pi-pi (2)<\/p>\n<\/td>\n

\n

TYR108PHE109
PHE112PHE182
TYR187LYS191
GLN194THR195
ILE198TRP248TYR
251LEU255ASN258
THR259MET279
GLU283<\/p>\n

Hydrogen (3), hydrophobic (9), weak hydrogen (1)<\/p>\n

<\/p>\n<\/td>\n

\n

LEU33TYR37
TRP86TYR89
THR105TYR108
PHE109ASN163
THR167ARG168
CYS178SER179
SER180GLU283
THR284MET287<\/p>\n

Hydrogen (4),
hydrophobic (13),
pi-pi (2) weak hydrogen (2)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

2NWG<\/p>\n<\/td>\n

\n

LEU29ASN30
THR31PRO32
GLN37ARG20
GLU60TYR61L
YS64ALA65ASN67<\/p>\n

Weak hydrogen (3),
ionic (2), hydrogen
(2), hydrophobic (4)<\/p>\n

<\/p>\n<\/td>\n

\n

LYS24HIS25LYS43
ChainB:TYR7PRO
10CYS11LYS27LEU
29ASN30THR31
VAL39GLN48 CYS50<\/p>\n

Weak hydrogen (1),
hydrogen (5),
hydrophobic (9),
<\/span>cation-pi (1)<\/span><\/p>\n<\/td>\n

\n

LYS1VAL3SER
6TYR7ARG8CYS
9PRO10ARG12LYS
27LEU29ASN30
THR31LYS24HIS25<\/p>\n

ARG41<\/p>\n

Weak (1), hydrogen (8),
hydrophobic (6), cation-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

6K3F<\/p>\n

<\/p>\n<\/td>\n

\n

ASP27ARG170
PHE174HIS212
GLU298ASP299
THR300ASN301
LEU302HIS212
GLY213PRO278
LEU279LEU280S
ER281ASP299
THR300ASN301<\/p>\n

Ionic (2), cation-pi (1),
hydrogen (3), hydrophobic
(7), weak hydrogen (1)<\/p>\n<\/td>\n

\n

ASP27ARG170HIS
212PRO278LEU279
LEU280GLU298ASP
299THR300ASN301
LEU302HIS212PRO
278LEU279LEU280
SER281ASP299<\/p>\n

THR300ASN301<\/p>\n

Ionic (1),
hydrogen (10),
hydrophobic (9)<\/p>\n

<\/p>\n<\/td>\n

\n

ASN225SER226
PRO266SER267A
SP30HIS31LEU32
ASP33LYS34VAL35
ILE120PRO121GLN
122ASN123LEU124
LYS171GLN173ILE
307 VAL308LYS309
GLU310<\/p>\n

Ionic (2),
cation-pi (1),
hydrogen (6),
hydrophobic (5),
weak (5)<\/p>\n

<\/p>\n<\/td>\n<\/tr>\n

\n

1JL9<\/p>\n<\/td>\n

\n

TYR44ILE38GLY
39GLU40TYR44
ARG45ASP46<\/p>\n

Pi-pi (1), ionic (1),
weak hydrogen (1),
hydrogen (1),
hydrophobic (5)<\/p>\n

<\/p>\n<\/td>\n

\n

ARG45CYS6PRO7
LEU8SER9HIS10
ASP11GLY12TYR
13CYS14LEU15HIS
16ASP17GLY18
VAL19CYS20<\/p>\n

Hydrogen (6),
hydrophobic (5),
weak hydrogen (5)<\/p>\n<\/td>\n

\n

CYS6PRO7LEU8SER
9HIS10ASP11GLY12
TYR13CYS14LEU15
ASP17GLY18 VAL19
CYS20<\/p>\n

Weak hydrogen (1),
hydrophobic (3),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

5O4G<\/p>\n<\/td>\n

\n

THR5GLY6THR7
ASP8GLN35GLY<\/p>\n

36GLN59GLN84
ASN280TYR281L
EU291GLY411AR
G412ILE413LEU
414GLY417SER441
GLY442<\/p>\n

Hydrogen (6), hydrophobic (8), ionic (2), weak hydrogen (2)<\/p>\n<\/td>\n

\n

ASP163THR164
ASN165ARG166
ARG168ALA169
TYR32SER91TYR
92SER93THR94T
RP47ARG50SER5
9ASP104SER105AL
A106 TRP107<\/p>\n

Hydrogen (7),
hydrophobic (4),
ionic (1), weak
hydrogen (3)<\/p>\n<\/td>\n

\n

THR1VAL3CYS4THR
5GLN35PRO278TYR
279ASN280TYR281
LEU291GY411ARG
412ILE413LEU414
GLY417GLY440SER
441ASN466HIS468<\/p>\n

Hydrogen (11), hydrophobic (8), weak hydrogen (8)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 10: Poses of singling proteins and targets<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Transcription\nfactors as targets<\/strong><\/em><\/p>\n\n\n\n

Vina score of\nquercetin seemed to be the highest when compared to the three drugs (Tables 15,\n16 and Fig. 11) for transcription factors20<\/sup>. Drug activation of ER\nbeta significantly inhibits cancer cell growth.\nHIF-1 activates cancer cell survival genes and allows them to grow in the\nhostile hypoxic tumor environment. Increased tumor HIF-1alpha has been linked\nto aggressive tumor growth, angiogenesis, and poor prognosis. Rb C-terminal\ndomain (RbC) is required for growth inhibition. Above 66% of breast\ncarcinomas express Er\u03b1, and majority ER+ tumors also express progesterone\nreceptors (PRs). Chemotherapy is rendered less effective due to ER mutations.\nPatients with advanced disease condition will have a high mutation rate. NF\u03baB\nencourages the development of an autonomous (hormone-independent), aggressive,\nhigh-grade, and late-stage tumor phenotype. The ER\u03b1’s anti-cancer properties are based on the sealing of its ligand binding domain20<\/sup>.<\/p>\n\n\n\n

Table 15: Transcription factor target classes used in the present study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Sl.No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.      <\/p>\n<\/td>\n

\n

Estrogen receptor<\/p>\n<\/td>\n

\n

7JHD<\/p>\n<\/td>\n

\n

251<\/p>\n<\/td>\n

\n

2.40 \u00c5<\/p>\n<\/td>\n

\n

A:-7.3;C:-7.7;Q:-8.3<\/p>\n<\/td>\n<\/tr>\n

\n

2.      <\/p>\n<\/td>\n

\n

Estrogen receptor<\/p>\n<\/td>\n

\n

6SBO<\/p>\n<\/td>\n

\n

260<\/p>\n<\/td>\n

\n

1.48 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9;C:-7.1;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

3.      <\/p>\n<\/td>\n

\n

Transcription factor Dp-1<\/p>\n<\/td>\n

\n

2AZE<\/p>\n<\/td>\n

\n

155<\/p>\n<\/td>\n

\n

2.55 \u00c5<\/p>\n<\/td>\n

\n

A:-7.1;C:-7.2;Q:-7.7<\/p>\n<\/td>\n<\/tr>\n

\n

4.      <\/p>\n<\/td>\n

\n

Protein (nuclear factor kappa-b (Nf-kB)<\/p>\n<\/td>\n

\n

1NFK<\/p>\n<\/td>\n

\n

325<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-8.4;Q:-9.6<\/p>\n<\/td>\n<\/tr>\n

\n

5.      <\/p>\n<\/td>\n

\n

Progesterone receptor<\/p>\n<\/td>\n

\n

4OAR<\/p>\n<\/td>\n

\n

258<\/p>\n<\/td>\n

\n

2.41 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9;C:-7.8;Q:-8.1<\/p>\n<\/td>\n<\/tr>\n

\n

6.      <\/p>\n<\/td>\n

\n

Estrogen receptor beta<\/p>\n<\/td>\n

\n

2I0G<\/p>\n<\/td>\n

\n

257<\/p>\n<\/td>\n

\n

2.50 \u00c5<\/p>\n<\/td>\n

\n

A:-8.6;C:-7.8;Q:-8.8<\/p>\n<\/td>\n<\/tr>\n

\n

7.      <\/p>\n<\/td>\n

\n

Estrogen receptor beta<\/p>\n<\/td>\n

\n

5TOA<\/p>\n<\/td>\n

\n

249<\/p>\n<\/td>\n

\n

2.50 \u00c5<\/p>\n<\/td>\n

\n

A:-7.4;C:-7.3;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

8.      <\/p>\n<\/td>\n

\n

Hypoxia-inducible factor 1 alpha inhibitor<\/p>\n<\/td>\n

\n

1YCI<\/p>\n<\/td>\n

\n

349<\/p>\n<\/td>\n

\n

2.70 \u00c5<\/p>\n<\/td>\n

\n

A:-8.1;C:-6.7;Q:-7.4<\/p>\n<\/td>\n<\/tr>\n

\n

9.      <\/p>\n<\/td>\n

\n

Stromal cell-derived factor 1 alpha<\/p>\n<\/td>\n

\n

2J7Z<\/p>\n<\/td>\n

\n

68<\/p>\n<\/td>\n

\n

1.95 \u00c5<\/p>\n<\/td>\n

\n

A:-6.2;C:-5.9;Q:-6.7<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 16: Poses, contact amino acids and varieties of bonds between the target and the ligand molecules belong to transcription factors involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues and bond pattern<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

5TOA<\/p>\n<\/td>\n

\n

GLU276
PRO277PRO
278 HIS279VAL
280LEU301GLU
305HIS308MET
309TRP312VAL
338LEU339GLY
342TRP345ARG
346PHE356ALA
357PRO358<\/p>\n

TYR397LYS401<\/p>\n

Hydrophobic (7),
weak hydrogen (4),
hydrophobic (6), ionic (1)<\/p>\n

<\/p>\n<\/td>\n

\n

GLU276PRO
277PRO278<\/p>\n

HIS279VAL280
LYS304GLU305
LEU306HIS308
MET309TRP312
VAL338LEU339
GLY342TRP345
ARG346HIS394<\/p>\n

TYR397LYS401<\/p>\n

Pi-pi (2) Hydrogen (4),
weak hydrogen (2),
hydrophobic (12),
ionic (1)<\/p>\n<\/td>\n

\n

MET295LEU
298THR<\/p>\n

299LEU301ALA302
GLU305MET336
LEU339MET340
LEU343ARG346
PHE356ILE373
ILE376LEU380
GLY472MET473
HIS475LEU476
MET479VAL485<\/p>\n

Hydrogen (8),
weak hydrogen (2),
hydrophobic (13),
ionic (1)<\/p>\n<\/td>\n<\/tr>\n

\n

1YCI<\/p>\n<\/td>\n

\n

TYR93PHE100
LEU101TYR102
TYR145GLN147
LEU186LEU188
VAL195THR196
PRO197HIS199
ASP201PHE207
ARG238ILE281
ASN294 TRP296<\/p>\n

Ionic (4), hydrophobic (10),
hydrogen (2), pi-pi (1),
weak hydrogen (5)<\/p>\n

<\/p>\n<\/td>\n

\n

TYR102TYR
145GLN147<\/p>\n

LEU186LEU188
THR196HIS199
ASP201GLU202
GLN203PHE207
ARG238ILE281
ASN294TRP296<\/p>\n

Pi-pi (1), cation-pi (1),
hydrogen (3),
hydrophobic (7)<\/p>\n

<\/p>\n<\/td>\n

\n

TYR93SER94
PHE100<\/p>\n

LEU101TYR102
TYR103SER118
TYR145GLN147
LEU188THR196
HIS199ASP201
ASN205PHE207
LYS214HIS279ILE
281ASN294<\/p>\n

TRP296<\/p>\n

Ionic (1), hydrophobic (13)
, weak hydrogen(4),
hydrogen (6), cation-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

2I0G<\/p>\n<\/td>\n

\n

MET295LEU298
THR299LEU301
ALA302GLU305
TRP335MET336
LEU339MET340
LEU343ARG346
PHE356ILE373
ILE376PHE377
LEU380GLY472
HIS475LEU476
VAL487<\/p>\n

Ionic (2), hydrophobic
(19), hydrogen (1),
pi-pi (1), weak hydrogen (2)<\/p>\n

<\/p>\n<\/td>\n

\n

GLU276
PRO277PRO278
HIS279GLU305
LEU306HIS308
MET309VAL338
LEU339GLY342
TRP345ARG346
HIS394TYR397
LYS401<\/p>\n

Ionic (1),
hydrophobic (17),
hydrogen (6),
weak hydrogen (1),
pi-pi (1)<\/p>\n

<\/p>\n<\/td>\n

\n

MET295LEU
298THR
299LEU301ALA302
GLU305MET336
LEU339MET340
LEU343ARG346
PHE356ILE373
ILE376LEU380
GLY472MET473
HIS475LEU476
MET479<\/p>\n

Ionic (1),
hydrophobic (14),
hydrogen (8),
pi-pi (1),
weak hydrogen (1)<\/p>\n<\/td>\n<\/tr>\n

\n

1NFK<\/p>\n<\/td>\n

\n

BLYS249VAL251
ARG252LEU<\/p>\n

269ASP271
LYS275PRO300
THR301ASP302
VAL303HIS304
ARG305GLN306
VAL310<\/p>\n

Pi-pi (6), cation-pi (2)
hydrogen (11)
weak hydrogen(4),
hydrophobic (4),
ionic (2)<\/p>\n

<\/p>\n<\/td>\n

\n

ARG161GLY
162ASN164<\/p>\n

PRO165GLY166
LEU167SER171
LEU173ALA174
TYR175LEU176
GLN177PHE217
THR226ARG228<\/p>\n

Pi-pi (13), ionic (3),
hydrogen (23)
weak hydrogen(13)
hydrophobic (11)<\/span><\/p>\n

<\/p>\n<\/td>\n

\n

GLY162
ASN164PRO<\/p>\n

165GLY166
LEU167SER
171LEU173
ALA174TYR175
LEU176GLN177
PHE217PHE225
THR226ARG227
ARG228GLU230<\/p>\n

Pi-pi (9), ionic (3),
hydrogen (21),
weak hydrogen (10),
hydrophobic (4)<\/p>\n<\/td>\n<\/tr>\n

\n

2AZE<\/p>\n<\/td>\n

\n

PHE233LEU259
PRO260PHE<\/p>\n

261ILE262ASP295
ASP296ILE297SER
235GLN241ALA267
PRO268PRO269
ChainC:SER834
ILE835GLY836
GLU837SER838
THR841<\/p>\n

Weak hydrogen (2),
hydrophobic (7)
ionic (2),
hydrogen (6)<\/p>\n<\/td>\n

\n

PHE233VAL
237LEU259<\/p>\n

PRO260PHE261
ILE262ASP295
ASP296ILE297
LEU234SER235
SER240GLN241
ALA244Chain
C:SER834ILE835
GLY836GLU837
SER838THR841<\/p>\n

Hydrogen (6),
weak hydrogen (2),
hydrophobic (14)<\/p>\n<\/td>\n

\n

PHE233VAL
237LEU259<\/p>\n

PRO260ASP295
ASP296ILE297
LEU231LEU234
SER235GLU236
SER240GLN241
ALA244ILE835
GLY836GLU837
SER838THR841<\/p>\n

Hydrogen (6),
hydrophobic (5),
weak hydrogen (1),
pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

6SBO<\/p>\n<\/td>\n

\n

MET343LEU346
THR347LEU349
ALA350TRP383
LEU384LEU387
MET388LEU391
PHE404VAL418
MET421ILE424
PHE425GLY521
LEU525MET528
ASN532 VAL533<\/p>\n

Hydrophobic (18),
hydrogen (1)<\/p>\n

<\/p>\n<\/td>\n

\n

MET343LEU
346THR347<\/p>\n

LEU349ALA350
ASP351GLU353
LEU354TRP383
LEU384LEU387
PHE404LEU525
ASN532VAL533
VAL534PRO535<\/p>\n

Hydrogen (4),
weak hydrogen (2),
hydrophobic (17)<\/p>\n

<\/p>\n<\/td>\n

\n

MET343LEU
346THR<\/p>\n

347LEU349ALA
350GLU353TRP
383LEU384LEU
387MET388ILE
389LEU391ARG
394PHE404LEU
428LEU525MET
528 VAL533<\/p>\n

Hydrogen (4),
hydrophobic (17),
pi-pi (1), weak
hydrogen (1),
ionic (1)<\/p>\n<\/td>\n<\/tr>\n

\n

4OAR<\/p>\n<\/td>\n

\n

GLU695
PRO696ASP697
VAL698ILE699
GLN725SER728
VAL729TRP732
LEU758MET759
GLY762TRP765
ARG766PHE778
ALA779PRO780
PHE818LYS822<\/p>\n

Hydrophobic (12),
pi-pi (2), weak
hydrogen (2),
ionic (1), hydrogen
(4), cation-pi (1)<\/p>\n<\/td>\n

\n

GLU276
PRO277PRO278<\/p>\n

HIS279GLU305
LEU306HIS308
MET309VAL338
LEU339GLY342
TRP345ARG346
HIS394TYR397
LYS401<\/p>\n

Pi-pi (2),
weak hydrogen (1),
hydrogen (3),
ionic (1),
cation-pi (2),
hydrophobic (15)<\/p>\n

<\/p>\n<\/td>\n

\n

PRO696ASP
697VAL<\/p>\n

698ILE699TYR
700LEU721GLN
725SER728VAL
729TRP732SER
757LEU758MET
759PHE761GLY
762LEU763
ARG766PHE778
ALA779PRO780
PHE818 LYS822<\/p>\n

Weak hydrogen (2),
hydrogen (9)
cation-pi (3),
hydrophobic (16)<\/p>\n<\/td>\n<\/tr>\n

\n

7JHD<\/p>\n<\/td>\n

\n

MET343LEU
345LEU346<\/p>\n

THR347LEU349
ALA350GLU353
TRP383LEU384
LEU387MET388
LEU391ARG394
PHE404ILE424
PHE425LEU428
GLY521LEU525
LEU540<\/p>\n

Ionic (1),
hydrogen (1),
hydrophobic (23)<\/p>\n

<\/p>\n<\/td>\n

\n

LEU320
GLU323PRO324<\/p>\n

PRO325ILE326
LEU327GLU353
LEU354HIS356
MET357TRP360
ILE386LEU387
GLY390TRP393
ARG394GLY442
PHE445VAL446
LYS449<\/p>\n

Cation-ion(2),
pi-pi (1), hydrogen (2),
weak hydrogen (3),
ionic (1),
hydrophobic (18)<\/p>\n

<\/p>\n<\/td>\n

\n

MET343LEU
345LEU<\/p>\n

346THR347LEU349
ALA350GLU353
LEU384LEU387
MET388LEU391
ARG394PHE404
VAL418GLY420
MET421ILE424
PHE425LEU428
GLY521HIS524
LEU525<\/p>\n

Pi-pi (2), ionic (1),
hydrogen (3),
weak hydrogen (2),
hydrophobic (11)<\/p>\n<\/td>\n<\/tr>\n

\n

2J7Z<\/p>\n<\/td>\n

\n

VAL3 PRO10
ARG12LYS27<\/p>\n

LEU29ASN30
THR31VAL39
GLN48LYS24 HIS25LYS27ARG41<\/p>\n

ASN46<\/p>\n

Hydrophobic (11)<\/p>\n

<\/p>\n<\/td>\n

\n

ARG20ALA21
VAL23 LYS<\/p>\n

43GLU60TYR61LYS
64ALA65Chain B: SER6TYR7ASN30
THR31 PRO32 GLN37<\/p>\n

Hydrophobic (11),
hydrogen (5), weak
hydrogen (1)<\/p>\n<\/td>\n

\n

VAL3
SER6TYR7ARG8<\/p>\n

CYS9PRO10
LEU29ASN
30THR31ASN
33CYS34VAL<\/p>\n

23LYS24
HIS25ARG41<\/p>\n

LYS43<\/p>\n

Hydrogen (9),
hydrophobic (5),
weak hydrogen (1)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 11: Binding poses of transcription factors in breast cancer cell lines with the ligands<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Transferases as targets<\/strong><\/em><\/p>\n\n\n\n

Quercetin\u2019s vina score is highest, with the proteins belonging to\ntransferases (Table 17, 18) (Fig. 12a and 12b). Somatic\ngenetic alterations most frequently activate CDK4 and cyclin D1 in a variety of\ntumor types. CDK4 is a genetically validated therapeutic target, since CDK4\/\ncyclin D1 pathway is important in oncogenesis. The estrogen receptor (ER) is\noverexpressed in breast cancer. In ER alpha-positive human breast cancer cells,\nstromal cell-derived factor 1 (SDF-1), (cytokine stimulator for growth) is a\ngenuine goal of estrogen\u2019s action. Cyclin-Dependent Kinases (CDKs) have been proposed\nas novel and promising target for cancer therapy. These, in conjugation with\ncyclins, show an important role in cell cycle advancement. CDK dysregulation\nresults in increased cell propagation, has been established in a number of\ncancers, no exception to BC. CDK1 selective inhibition is linked to potent\nanti-cancer outcomes either combined with other therapeutics or alone. VEGF\npromotes vessel proliferation, invasion and survival and endothelial cell\nproliferation. Tumor cell shape, proliferation, motility, progression and\nmetastasis depend on overexpressed Rho-associated protein kinase 1.\nCyclin-dependent kinases (CDKs) regulate cell cycle, apoptosis, transcription\nand neuronal functions. EphA2 Receptor\nProtein Kinase regulates cytoskeleton dynamics, cell\nadhesion, proliferation, differentiation, and metastasis. JAK2 regulates gene\nexpression in the G1 cell cycle, proliferation, oncogenesis, anti-apoptosis,\nangiogenesis and metastasis. EphA2 tyrosine kinase is involved in angiogenesis,\ncancer, and inflammation20<\/sup>. <\/p>\n\n\n\n

Table 17: Transferase target classes used in the present study<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Sl. No.<\/strong><\/p>\n<\/td>\n

\n

Protein molecule<\/strong><\/p>\n<\/td>\n

\n

RCSB id<\/strong><\/p>\n<\/td>\n

\n

Length<\/strong><\/p>\n<\/td>\n

\n

Resolution<\/strong><\/p>\n<\/td>\n

\n

Vina score of the drugs used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1.<\/p>\n<\/td>\n

\n

Cell division protein kinase 2<\/p>\n<\/td>\n

\n

2BHH<\/p>\n<\/td>\n

\n

298<\/p>\n<\/td>\n

\n

2.60 \u00c5<\/p>\n<\/td>\n

\n

A:-8.8;C: 7.9;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

2.<\/p>\n<\/td>\n

\n

Vascular endothelial growth factor A<\/p>\n<\/td>\n

\n

4KZN<\/p>\n<\/td>\n

\n

104<\/p>\n<\/td>\n

\n

1.71 \u00c5<\/p>\n<\/td>\n

\n

A:-5.5;C:-5.8;Q:-6.0<\/p>\n<\/td>\n<\/tr>\n

\n

3.<\/p>\n<\/td>\n

\n

Rho-associated protein kinase 1<\/p>\n<\/td>\n

\n

3TWJ<\/p>\n<\/td>\n

\n

410<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-8.8;C:-7.5;Q:-8.9<\/p>\n<\/td>\n<\/tr>\n

\n

4.<\/p>\n<\/td>\n

\n

Epidermal growth factor receptor<\/p>\n<\/td>\n

\n

2ITX<\/p>\n<\/td>\n

\n

327<\/p>\n<\/td>\n

\n

2.98 \u00c5<\/p>\n<\/td>\n

\n

A:-7.6;C:-7.1;Q:-8<\/p>\n<\/td>\n<\/tr>\n

\n

5.<\/p>\n<\/td>\n

\n

Peptidyl-prolyl cis-trans isomerase FKBP5<\/p>\n<\/td>\n

\n

4DRH<\/p>\n<\/td>\n

\n

144<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4;C:-8.5;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

6.<\/p>\n<\/td>\n

\n

Dual specificity mitogen-activated protein kinase kinase 1<\/p>\n<\/td>\n

\n

1S9J<\/p>\n<\/td>\n

\n

341<\/p>\n<\/td>\n

\n

2.40 \u00c5<\/p>\n<\/td>\n

\n

A:-6.7;C:-7.5;Q:-8.6<\/p>\n<\/td>\n<\/tr>\n

\n

7.<\/p>\n<\/td>\n

\n

Nicotinamide phosphoribosyl transferase<\/p>\n<\/td>\n

\n

2GVG<\/p>\n<\/td>\n

\n

491<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4;C:-8.8;Q:-10.1<\/p>\n<\/td>\n<\/tr>\n

\n

8.      <\/p>\n<\/td>\n

\n

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, gamma isoform<\/p>\n<\/td>\n

\n

2A5U<\/p>\n<\/td>\n

\n

966<\/p>\n<\/td>\n

\n

2.70 \u00c5<\/p>\n<\/td>\n

\n

A:-9.6;C:-7.8;Q:-9.3<\/p>\n<\/td>\n<\/tr>\n

\n

9.      <\/p>\n<\/td>\n

\n

Mitogen-activated protein kinase 14<\/p>\n<\/td>\n

\n

4FA2<\/p>\n<\/td>\n

\n

383<\/p>\n<\/td>\n

\n

2.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.7;C:-7.8;Q:-9.2<\/p>\n<\/td>\n<\/tr>\n

\n

10.   <\/p>\n<\/td>\n

\n

Ephrin type-A receptor 2<\/p>\n<\/td>\n

\n

1MQB<\/p>\n<\/td>\n

\n

333<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-7.6;C:-7.2;Q:-7.5<\/p>\n<\/td>\n<\/tr>\n

\n

11.   <\/p>\n<\/td>\n

\n

epidermal growth factor receptor<\/p>\n<\/td>\n

\n

1M17<\/p>\n<\/td>\n

\n

333<\/p>\n<\/td>\n

\n

2.60 \u00c5<\/p>\n<\/td>\n

\n

A:-7.7;C:-6.7;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

12.   <\/p>\n<\/td>\n

\n

Vascular endothelial growth factor receptor 2<\/p>\n<\/td>\n

\n

1YWN<\/p>\n<\/td>\n

\n

316<\/p>\n<\/td>\n

\n

1.71 \u00c5<\/p>\n<\/td>\n

\n

A:-7.2;C:-6.9;Q:-7.9<\/p>\n<\/td>\n<\/tr>\n

\n

13.   <\/p>\n<\/td>\n

\n

v-akt murine thymoma viral oncogene homolog 1 (AKT1)<\/p>\n<\/td>\n

\n

3MV5<\/p>\n<\/td>\n

\n

342<\/p>\n<\/td>\n

\n

2.47 \u00c5<\/p>\n<\/td>\n

\n

A:-8.4;C:-8;Q:-8.2<\/p>\n<\/td>\n<\/tr>\n

\n

14.   <\/p>\n<\/td>\n

\n

Phosphatidylinositol-4,5-bisphosphate 3-kinase<\/p>\n<\/td>\n

\n

3OAW<\/p>\n<\/td>\n

\n

966<\/p>\n<\/td>\n

\n

2.75 \u00c5<\/p>\n<\/td>\n

\n

A:-9.6;C:-7.6;Q:-8.3<\/p>\n<\/td>\n<\/tr>\n

\n

15.   <\/p>\n<\/td>\n

\n

Inhibitor of nuclear factor kappa-B kinase subunit beta<\/p>\n<\/td>\n

\n

4KIK<\/p>\n<\/td>\n

\n

677<\/p>\n<\/td>\n

\n

2.83 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9;C:-7.4;Q:-8.5<\/p>\n<\/td>\n<\/tr>\n

\n

16.   <\/p>\n<\/td>\n

\n

v-akt murine thymoma viral oncogene homolog 1 (AKT1)<\/p>\n<\/td>\n

\n

3OCB<\/p>\n<\/td>\n

\n

341<\/p>\n<\/td>\n

\n

2.70 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-8.1;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

17.   <\/p>\n<\/td>\n

\n

Epidermal growth factor receptor<\/p>\n<\/td>\n

\n

4WKQ<\/p>\n<\/td>\n

\n

330<\/p>\n<\/td>\n

\n

1.85 \u00c5<\/p>\n<\/td>\n

\n

A:-7.2;C:-6.6;Q:-8.3<\/p>\n<\/td>\n<\/tr>\n

\n

18.   <\/p>\n<\/td>\n

\n

Ephrin type-A receptor 4<\/p>\n<\/td>\n

\n

4M4P<\/p>\n<\/td>\n

\n

518<\/p>\n<\/td>\n

\n

 <\/strong>2.08 \u00c5<\/p>\n<\/td>\n

\n

A:-6;C:-6.4;Q:-6.7<\/p>\n<\/td>\n<\/tr>\n

\n

19.   <\/p>\n<\/td>\n

\n

RAC-alpha serine\/threonine-protein kinase<\/p>\n<\/td>\n

\n

3CQW<\/p>\n<\/td>\n

\n

342<\/p>\n<\/td>\n

\n

2.00 \u00c5<\/p>\n<\/td>\n

\n

A:-8.5;C:-7.9;Q:-8.5<\/p>\n<\/td>\n<\/tr>\n

\n

20.   <\/p>\n<\/td>\n

\n

Cell division protein kinase 6<\/p>\n<\/td>\n

\n

3NUP<\/p>\n<\/td>\n

\n

307<\/p>\n<\/td>\n

\n

2.60 \u00c5<\/p>\n<\/td>\n

\n

A:-8.3;C:-6.8;Q:-8.6<\/p>\n<\/td>\n<\/tr>\n

\n

21.<\/p>\n<\/td>\n

\n

Cyclin-dependent kinase 2<\/p>\n<\/td>\n

\n

1DI8<\/p>\n<\/td>\n

\n

298<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-9.3;C:-7.9;Q:-10<\/p>\n<\/td>\n<\/tr>\n

\n

22.<\/p>\n<\/td>\n

\n

cyclin D1-cyclin-dependent kinase 4 (CDK4) (G1\/S-Specific cyclin-D1)<\/p>\n<\/td>\n

\n

2W96<\/p>\n<\/td>\n

\n

271<\/p>\n<\/td>\n

\n

2.30 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9,C:-7.4,Q:-9.2<\/p>\n<\/td>\n<\/tr>\n

\n

23.<\/p>\n<\/td>\n

\n

Cyclin-dependent kinase 6<\/p>\n<\/td>\n

\n

1XO2<\/p>\n<\/td>\n

\n

254<\/p>\n<\/td>\n

\n

2.90 \u00c5<\/p>\n<\/td>\n

\n

A:-9.2;C:-8;Q:-10.6<\/p>\n<\/td>\n<\/tr>\n

\n

24.<\/p>\n<\/td>\n

\n

Epidermal growth factor receptor<\/p>\n<\/td>\n

\n

2J6M<\/p>\n<\/td>\n

\n

327<\/p>\n<\/td>\n

\n

3.10 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9;C:-7.2;Q:-8.4<\/p>\n<\/td>\n<\/tr>\n

\n

25.<\/p>\n<\/td>\n

\n

Protein (CDK2 human)<\/p>\n<\/td>\n

\n

1BUH<\/p>\n<\/td>\n

\n

298<\/p>\n<\/td>\n

\n

2.60 \u00c5<\/p>\n<\/td>\n

\n

A:-7.7;C:-7.8;Q:-8.3<\/p>\n<\/td>\n<\/tr>\n

\n

26.<\/p>\n<\/td>\n

\n

Receptor tyrosine-protein kinase erbB-2<\/p>\n<\/td>\n

\n

3PP0<\/p>\n<\/td>\n

\n

338<\/p>\n<\/td>\n

\n

2.25 \u00c5<\/p>\n<\/td>\n

\n

A:-8.7;C:-9.2;Q:-9.4<\/p>\n<\/td>\n<\/tr>\n

\n

27.<\/p>\n<\/td>\n

\n

Vascular endothelial growth factor receptor 2<\/p>\n<\/td>\n

\n

2OH4<\/p>\n<\/td>\n

\n

316<\/p>\n<\/td>\n

\n

2.05 \u00c5<\/p>\n<\/td>\n

\n

A:-7.5;C:-7.4;Q:-9.6<\/p>\n<\/td>\n<\/tr>\n

\n

28.<\/p>\n<\/td>\n

\n

RAC-alpha serine\/threonine-protein kinase<\/p>\n<\/td>\n

\n

3O96<\/p>\n<\/td>\n

\n

446<\/p>\n<\/td>\n

\n

2.70 \u00c5<\/p>\n<\/td>\n

\n

A:-9.9;C:-8.1;Q:-9.7<\/p>\n<\/td>\n<\/tr>\n

\n

29.<\/p>\n<\/td>\n

\n

RAC-alpha serine\/threonine-protein kinase<\/p>\n<\/td>\n

\n

3CQU<\/p>\n<\/td>\n

\n

342<\/p>\n<\/td>\n

\n

2.20 \u00c5<\/p>\n<\/td>\n

\n

A:-8;C:-7.9;Q:-9.2<\/p>\n<\/td>\n<\/tr>\n

\n

30.<\/p>\n<\/td>\n

\n

RAC-alpha serine\/threonine-protein kinase<\/p>\n<\/td>\n

\n

3OW4<\/p>\n<\/td>\n

\n

341<\/p>\n<\/td>\n

\n

2.60 \u00c5<\/p>\n<\/td>\n

\n

A:-7.8;C:-7.3;Q:-8.1<\/p>\n<\/td>\n<\/tr>\n

\n

31.<\/p>\n<\/td>\n

\n

Epidermal growth factor receptor<\/p>\n<\/td>\n

\n

5FED<\/p>\n<\/td>\n

\n

328<\/p>\n<\/td>\n

\n

2.65 \u00c5<\/p>\n<\/td>\n

\n

A:-8.2;C:-7;Q:-7.9<\/p>\n<\/td>\n<\/tr>\n

\n

32.<\/p>\n<\/td>\n

\n

Ephrin a2 (epha2) receptor protein kinase<\/p>\n<\/td>\n

\n

5NKA<\/p>\n<\/td>\n

\n

306<\/p>\n<\/td>\n

\n

1.38 \u00c5<\/p>\n<\/td>\n

\n

A:-7;C:-6.6;Q:-7.9<\/p>\n<\/td>\n<\/tr>\n

\n

33.<\/p>\n<\/td>\n

\n

Glutathione S-transferase P<\/p>\n<\/td>\n

\n

2A2R<\/p>\n<\/td>\n

\n

210<\/p>\n<\/td>\n

\n

1.40 \u00c5<\/p>\n<\/td>\n

\n

A:-7.3;C:-7.1;Q:-7.9<\/p>\n<\/td>\n<\/tr>\n

\n

34.<\/p>\n<\/td>\n

\n

Ribosomal protein S6 kinase alpha-3<\/p>\n<\/td>\n

\n

3G51<\/p>\n<\/td>\n

\n

325<\/p>\n<\/td>\n

\n

1.80 \u00c5<\/p>\n<\/td>\n

\n

A:-7.8; C:-7.5;Q:-8.3<\/p>\n<\/td>\n<\/tr>\n

\n

35.<\/p>\n<\/td>\n

\n

Tyrosine-protein kinase JAK2<\/p>\n<\/td>\n

\n

3KRR<\/p>\n<\/td>\n

\n

295<\/p>\n<\/td>\n

\n

1.80 \u00c5<\/p>\n<\/td>\n

\n

A:-7.9;C:-7.5;Q:-9.1<\/p>\n<\/td>\n<\/tr>\n

\n

36.<\/p>\n<\/td>\n

\n

Cyclin-dependent kinase 1<\/p>\n<\/td>\n

\n

4YC3<\/p>\n<\/td>\n

\n

302<\/p>\n<\/td>\n

\n

2.7 \u00c5<\/p>\n<\/td>\n

\n

A:-7.6;C:-7.1;Q:-9.5<\/p>\n<\/td>\n<\/tr>\n

\n

37.<\/p>\n<\/td>\n

\n

EphA2 ligand-binding domain (LBD)<\/p>\n<\/td>\n

\n

6NJZ<\/p>\n<\/td>\n

\n

187<\/p>\n<\/td>\n

\n

1.90 \u00c5<\/p>\n<\/td>\n

\n

A:-7.4; C:-7.8; Q:-8.4<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 18: Contact amino acids and varieties of bonds between the target and the ligand molecules belong to transferases involved in breast cancer.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

PDB<\/strong><\/p>\n<\/td>\n

\n

Contact residues and bond pattern<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anastrazole<\/strong><\/p>\n<\/td>\n

\n

Capecitabine<\/strong><\/p>\n<\/td>\n

\n

Quercetin<\/p>\n<\/td>\n<\/tr>\n

\n

2W96<\/p>\n<\/td>\n

\n

LEU6CYS8ILE
13ARG26VAL27
ARG29ALA30LYS
33PHE66 HIS68
ASP129 PHE130
ALA133 ASN134<\/p>\n

Hydrophobic (11),
weak hydrogen (1),
ionic (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE12GLY13VAL
14GLY15ALA16TYR
17VAL20ALA33LYS
35VAL72PHE93GLU
94HIS95VAL96ASP
99ARG101ASP140
LYS142GLU144ASN
145LEU147ALA157
ASP158<\/p>\n

Hydrophobic (7),
ionic (1),
weak hydrogen (3),
hydrogen (6)<\/p>\n<\/td>\n

\n

ILE12GLY15ALA16T
YR17VAL20ALA33LY
S35HIS95VAL96ASP9
7GLN98ASP99ARG101
THR102ASP140LYS142
GLU144ASN145LEU147<\/p>\n

ASP158<\/p>\n

Weak hydrogen (7),
hydrogen (12),
hydrophobic (7),
<\/span>ionic (3)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

3TWJ<\/p>\n<\/td>\n

\n

ILE82
GLY83VAL90
ALA<\/p>\n

103MET128
VAL137MET
153GLU154
TYR155MET
156ASP160
ASP202ASN
203LEU205
ALA215ASP
216PHE368<\/p>\n

Hydrophobic (14),
weak hydrogen (2),
hydrogen (1), 
ionic (2)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE82
GLY83ARG84GLY<\/p>\n

85VAL90LEU92
ALA103LYS105
MET128VAL137
MET153GLU154
TYR155MET156
ASP160ASP202
LEU205ALA215
ASP216PHE368<\/p>\n

Hydrophobic (20),
weak hydrogen (1),
hydrogen (1),
ionic (1)<\/p>\n<\/td>\n

\n

ILE82 VAL90
LEU92TYR<\/p>\n

102ALA103LYS105
VAL137MET153G
LU154TYR155MET
156ASP160VAL162
ASP202LEU205AL
A215ASP216 PHE368<\/p>\n

Hydrophobic (18),
weak hydrogen (2),
hydrogen (3),  ionic (1)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

1BUH<\/p>\n<\/td>\n

\n

ILE10GLY11GLU
12GLY13VAL18
TYR19ALA1LYS
33PHE80GLU
81PHE82LEU83
HIS84ASP86GLN
131ASN132LEU
133LEU134ALA
144ASP145<\/p>\n

Ionic (3), hydrophobic
(15), weak hydrogen
(2), hydrogen (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE10
GLU12GLY13 THR<\/p>\n

14VAL18TYR19
ALA31LYS33<\/p>\n

PHE80GLU81
PHE82LEU83
ASP86LYS129
GLN131ASN132
LEU134ALA144
ASP145THR158
TYR159GLU162
VAL163<\/p>\n

Ionic (2),
hydrophobic (9),
weak hydrogen (4),
hydrogen (6)<\/p>\n<\/td>\n

\n

ILE10GLY11GLU
12GLY13THR14V
AL18ALA31LYS33
PHE80GLU81PHE2
LEU83HIS84GLN85
ASP86ASP127LYS129
GLN131ASN132LEU
134ASP145<\/p>\n

Ionic (1),
hydrophobic (10),
weak hydrogen (3),
<\/span>hydrogen (6)<\/p>\n<\/td>\n<\/tr>\n

\n

4YC3<\/p>\n<\/td>\n

\n

GLN184ALA
185VAL186 TY<\/p>\n

R223MET224
VAL226SER227
ASP230ARG231
ARG298PRO299
LEU300PRO301
MET326THR329
MET330MET335
VAL336PHE338
PRO340 ILE343<\/p>\n

Hydrogen (7),
weak hydrogen (3),
hydrophobic (13)<\/p>\n

 <\/p>\n<\/td>\n

\n

GLU181GLU
182GLN184<\/p>\n

ALA185VAL186
TYR223MET224
VAL226SER227
ARG298PRO299
LEU300PRO301
MET335VAL336
HIS337PHE338
PRO339PRO340<\/p>\n

Hydrogen (2),
weak hydrogen (6),
hydrophobic (8),
cation-pi (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU180GLU181GL
U182GLN184ALA
185ARG201TYR223
MET224VAL226SER
227ASP230ARG298
PRO299LEU300PRO
301THR329MET330
ASP332TYR333ASP
334MET335VAL336
PHE338
PRO340ILE343<\/p>\n

Hydrogen (10),
weak hydrogen (3),
hydrophobic (14),
ionic (1)<\/p>\n<\/td>\n<\/tr>\n

\n

4KZN<\/p>\n<\/td>\n

\n

GLU38
TYR39ARG56GLU<\/p>\n

73ASN75SER
95PHE96LEU97<\/p>\n

Ionic (1), hydrogen,
hydrophobic (5),
weak hydrogen (2)<\/p>\n

 <\/p>\n<\/td>\n

\n

CYS57GLY58
GLY59CYS60
CYS61ASN62
ASP63GLU64
GLY65LEU66
GLU67 CYS68
VAL69LYS107<\/p>\n

Hydrogen (7),
hydrophobic (3),
weak hydrogen (1)<\/p>\n<\/td>\n

\n

CYS26GLY59CYS60C
YS61ASN62ASP63
GLU64 LEU66GLU67
CYS68CYS104 LYS107<\/p>\n

Hydrogen (6),
hydrophobic (3),
weak hydrogen (2)<\/p>\n<\/td>\n<\/tr>\n

\n

1XO2<\/p>\n<\/td>\n

\n

ILE19GLY20
GLU21GLY22<\/p>\n

GLY25VAL27
ALA41LEU42LYS
43GLU61VAL77
PHE98GLU99HIS
100VAL101GLN
103ASP104LYS147
GLN149ASN150
LEU152 ALA162
ASP163<\/p>\n

Hydrophobic (13),
weak hydrogen (1),
hydrogen,  ionic (2)<\/p>\n<\/td>\n

\n

ILE19
GLY20VAL27ALA<\/p>\n

41LYS43GLU
61VAL77PHE98<\/p>\n

GLU99HIS100
VAL101ASP102
GLN103ASP104
THR107GLN149
ASN150LEU152
ALA162ASP163
PHE164<\/p>\n

Hydrophobic (13),
weak hydrogen (2),
hydrogen (6), 
ionic (2)<\/p>\n<\/td>\n

\n

ILE19 GLY20VAL27
ALA41LYS43GLU61
VAL77PHE98GLU99
HIS100VAL101ASP1
02GLN103ASP104T
HR107GLN149ASN1
50LEU152ALA162A
SP163PHE164<\/p>\n

Hydrophobic (12),
weak hydrogen (1),
hydrogen (11), 
ionic (2)<\/p>\n<\/td>\n<\/tr>\n

\n

4DHR<\/p>\n<\/td>\n

\n

TYR57 PHE67
ASP68 HIS71
PHE77 TYR113
PRO120 PHE130SER
2035TYR2038PHE
2039LEU2097
THR2098 TRP2101
ASP2102TYR2105<\/p>\n

Ionic (1), hydrophobic
(11),weak hydrogen (2),
hydrogen (2), ionic (3)<\/p>\n<\/td>\n

\n

TYR57ASP68
SER70HIS71<\/p>\n

PHE77PRO
120LEU2031<\/p>\n

GLU2032SER
2035PHE2039
LEU2097THR
2098TRP2101
ASP2102TYR
2104TYR2105<\/p>\n

PHE2108<\/p>\n

Hydrophobic (17),
weak hydrogen (4),
hydrogen (5),
pi-pi (1), ionic (1)<\/p>\n<\/td>\n

\n

ASP68HIS71PHE77
VAL78GLN85LEU20
31GLU2032SER2035
PHE2039 LEU2097
THR2098GLN2099T
RP2101 ASP 2102TY
R2104<\/p>\n

TYR2105PHE2108<\/p>\n

Ionic (2),
hydrophobic (8),
weak hydrogen (5),
hydrogen (4), pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

2ITX<\/p>\n<\/td>\n

\n

LEU718VAL726ALA
743GLU762MET766
CYS775LEU788THR
790GLN791LEU792
MET793GLY796CYS
797ARG841 ASN842<\/p>\n

LEU844THR854
ASP855<\/p>\n

Ionic (3), hydrophobic
(10), weak hydrogen (4),
hydrogen (7)<\/p>\n

 <\/p>\n<\/td>\n

\n

ALA702LEU703
LEU704MET766
ALA767SER768
VAL769ASP770
ASN771PRO772
ARG776LYS852
ALA1013ASP10
14TYR1016LEU
1017ILE1018<\/p>\n

PRO1019<\/p>\n

Ionic (1),
hydrophobic (5),
weak hydrogen (1),
hydrogen (6),
cation-pi (1)<\/p>\n<\/td>\n

\n

LEU718GLY719VAL
726ALA743LYS745
GLU762MET766LE
U788THR790GLN79
1LEU792MET793PR
O794PHE795GLY79
6LEU844THR854
ASP855<\/p>\n

Ionic (1),
hydrophobic (8),
weak hydrogen (1),
hydrogen (6)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

2BHH<\/p>\n<\/td>\n

\n

ILE10 GLY11
GLU12VAL18<\/p>\n

ALA31LYS33VAL
64PHE80GLU81
PHE82LEU83HIS
84GLN85ASP86
GLN131ASN132
LEU134ALA144
ASP145<\/p>\n

Ionic (2), hydrophobic (17),
weak hydrogen (2),
pi-pi (1), ionic (2)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE10GLY11VAL
18ALA31LYS33
VAL64PHE80
GLU81PHE82
LEU83HIS84
GLN85ASP86
LYS89GLN131
ASN132LEU134
ALA144ASP145<\/p>\n

Ionic (1),
hydrophobic (20),
weak hydrogen (5),
hydrogen (5),
pi-pi (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE10GLY11GLU12
GLY13THR14TYR15
GLY16VAL18ALA31
LYS33VAL64PHE80
GLU81ASP127LYS129
GLN131ASN132LEU
134ALA144ASP145<\/p>\n

Ionic (2),
hydrophobic (13),
weak hydrogen (1),
hydrogen (10)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

1S9J<\/p>\n<\/td>\n

\n

LEU74GLY75ALA76
GLY77VAL82ALA95
LYS97MET143GLU
144HIS145MET146
GLY149SER150ASP
152GLN153SER194
ASN195LEU197CYS
207ASP208<\/p>\n

Ionic (1), hydrophobic (11),
weak hydrogen (3),
hydrogen (7)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU74GLY75
ALA76GLY77
ASN78GLY79
GLY80VAL82
ALA95LYS97
LEU98ILE99
MET143MET146
GLY149SER150
ASP152GLN153
SER194ASN195
LEU197CYS207
ASP208<\/p>\n

Ionic (1),
hydrophobic (9),
weak hydrogen (4),
hydrogen (10)<\/p>\n<\/td>\n

\n

LEU74GLY75ALA76
GLY77VAL82ALA95
LYS97VAL127MET1
43GLU144HIS145M
ET146ASP147GLY14
9SER150GLN153SER
194ASN195LEU197
ASP208<\/p>\n

Ionic (1),
hydrophobic (7),
weak hydrogen (2),
hydrogen (8)<\/p>\n<\/td>\n<\/tr>\n

\n

2GVG<\/p>\n<\/td>\n

\n

ASP192PHE193GLY
194ARG196GLY197
ASP219HIS247ARG
311ASP313GLY353
ASP354GLY355GLY
381SER382GLY383
GLY384ASP16TYR18
GLU149ARG392SER
398LYS415LYS423<\/p>\n

Ionic (12), cation-pi (1) 
hydrophobic (5),
weak hydrogen (4),
hydrogen (7)<\/p>\n

 <\/p>\n<\/td>\n

\n

ASP16TYR18
ARG392ASP393
ASP192PHE193
GLY194ARG196
ASP219ARG311
ASP313GLY353
ASP354GLY355
VAL356ASP357
SER382GLY383
GLY384GLY385
LYS389<\/p>\n

Ionic (4),
hydrophobic (6),
weak hydrogen (3),
hydrogen bonds (9),  
cation-pi (2)<\/p>\n<\/td>\n

\n

ASP16TYR18ARG392
SER398LYS400LYS415
HIS191ASP192PHE193
ARG196ASP219ALA244
HIS247ARG311ASP313<\/p>\n

Ionic (4),
hydrophobic (3),
weak hydrogen
bond (4), hydrogen (12),
pi-pi (2) cation-pi (2)<\/span><\/p>\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

3MV5<\/p>\n<\/td>\n

\n

GLY157LYS158
GLY159THR160
PHE161GLY162
LYS163VAL164
LYS179LEU181
GLU191HIS194
GLU198ASP274
LYS276ASP292
PHE293GLY294
LEU295THR5T
HR6SER7<\/p>\n

Pi-pi (1), ionic (5),
hydrophobic (6),
weak hydrogen (2),
hydrogen (4)<\/p>\n<\/td>\n

\n

LYS158GLY159
PHE161LYS179
LEU181ILE186
GLU191HIS194
THR195GLU198
GLU234ASP274
LYS276GLU278
ASN279ASP292
PHE293GLY294
LEU295ARG4THR
5THR6SER7<\/p>\n

Ionic (3),
hydrogen (10),
hydrophobic (9),
weak hydrogen (4)<\/p>\n<\/td>\n

\n

GLY157LYS158GLY
159PHE161VAL164
GLU191HIS194GLU
234ASP274LYS276G
LU278ASN279THR2
91ASP292PHE293GL
Y294LEU295PHE442
ARG4THR5SER7<\/p>\n

Ionic (4),
hydrophobic (3),
hydrogen (12)<\/p>\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

1MQB<\/p>\n<\/td>\n

\n

ILE619GLY620
ALA621GLY622
VAL627ALA644
LYS646GLU66
MET667ILE676
THR692GLU693
TYR694MET695
GLY698ALA699
ARG743ASN744
LEU746SER756
ASP757<\/p>\n

Ionic (3), hydrophobic
(11), hydrogen (5),
weak hydrogen (4)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE619GLY622GLU
623VAL627ALA644
LYS646GLU663TYR
694MET695GLU696
GLY698ASN744LEU
746SER756ASP757
PHE758<\/p>\n

Hydrophobic (6),
hydrogen (5) 
weak hydrogen (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE619GLY622GLU
623VAL627VAL643
ALA644LYS646ILE
676THR692GLU693
TYR694MET695GLU
696ASN697GLY698
ALA699ARG743ASN
744LEU746SER756
ASP757<\/p>\n

Ionic (1),
hydrophobic (14),
weak hydrogen (3),
hydrogen (5),
cation-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

3NUP<\/p>\n<\/td>\n

\n

ILE19GLY20VAL
27ALA41LYS43
VAL77PHE98
GLU99HIS100
VAL101GLN103
ASP104GLN149
ASN150LEU152
ALA162<\/p>\n

ASP163
PHE164<\/p>\n

Ionic (4)
hydrophobic (12),
weak hydrogen (2)<\/p>\n

 <\/p>\n<\/td>\n

\n

ILE19GLY20VAL27
LYS29ALA41LYS43
VAL77PHE98GLU99
HIS100VAL101ASP102
GLN103ASP104THR107
GLN149LEU152ALA162
ASP163<\/p>\n

Ionic (2),
hydrophobic (14),
hydrogen (3),
weak hydrogen (2)<\/span><\/p>\n<\/td>\n

\n

ILE19VAL27ALA41
LYS43VAL77PHE98
GLU99HIS100VAL
101ASP102GLN103
ASP104THR107LEU
152ALA162ASP163<\/p>\n

Ionic (2),
hydrophobic (8),
weak hydrogen (1),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

1M17<\/p>\n<\/td>\n

\n

LEU694PHE699
VAL702ALA719
LYS721GLU738
MET742CYS751
LEU764THR766
LEU768MET769
GLY772CYS773
ARG817LEU820
THR830 ASP831<\/p>\n

Ionic (4), hydrogen (5),
hydrophobic (8),
weak hydrogen (3)<\/p>\n<\/td>\n

\n

LEU694VAL702
LYS704ALA719
LYS721GLU738
THR766GLN767
LEU768MET769
PRO770PHE771
GLY772CYS773A
RG817LEU820THR
830 ASP831<\/p>\n

Hydrophobic (7),
ionic (2) weak
hydrogen (5),
hydrogen (5)<\/p>\n<\/td>\n

\n

LEU694VAL702ALA
719ILE720LYS721G
LU738MET742LEU7
64ILE765THR766LE
U768MET769PRO77
0GLY772CYS773LEU
820THR830 ASP831<\/p>\n

Ionic (2),
hydrophobic (6),
weak hydrogen (5),
hydrogen (6)<\/p>\n<\/td>\n<\/tr>\n

\n

1YWN<\/p>\n<\/td>\n

\n

LYS866GLU883
ILE886LEU887
ILE890VAL896
VAL897LEU1017
CYS1022ILE1023
HIS1024ARG1025
ILE1042CYS1043
ASP1044<\/p>\n

Ionic (8), hydrogen (1),
hydrophobic (8)<\/p>\n

 <\/p>\n<\/td>\n

\n

TRP1094TYR1104
PRO1105VAL1107
PHE1113ARG1116
LEU1117THR1121
ARG112MET1123
ARG1124ALA1125
PRO1126 ASP1127<\/p>\n

Hydrophobic (7),
hydrogen (11), 
weak hydrogen (4),
cation-pi (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU838GLY839VAL
846ALA864LYS866
GLU883LEU887VAL
897VAL914GLU915
PHE916CYS917LYS
918GLY920LEU1033
CYS1043ASP1044<\/p>\n

Ionic (1),
hydrophobic (13),
weak hydrogen (1),
hydrogen (3)<\/p>\n<\/td>\n<\/tr>\n

\n

4WKQ<\/p>\n<\/td>\n

\n

LEU718GLY719
VAL726ALA743
ILE744LYS745
GLU762<\/p>\n

MET766CYS775
THR790LEU792
MET793GLY796
LEU844<\/p>\n

THR854<\/p>\n

Hydrophobic (11),
hydrogen (2),
ionic (1),
weak hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU718GLY719
VAL726ALA743I
LE744LYS745GLU
762MET766LEU
788ILE789THR
790MET793GLY
796ARG841LEU
844THR854ASP855<\/p>\n

Ionic (1), hydrophobic (11),
weak hydrogen (5),
hydrogen (2)<\/p>\n<\/td>\n

\n

LEU718GLY719VAL
726ALA743LYS745
GLU762MET766LEU
788THR790GLN791
LEU792MET793PRO
794PHE795GLY796
LEU844THR854
ASP855<\/p>\n

Hydrophobic (6),
weak hydrogen (3),
hydrogen (6), ionic (2)<\/p>\n<\/td>\n<\/tr>\n

\n

2J6M<\/p>\n<\/td>\n

\n

LEU718PHE723
VAL726ALA743
LYS745GLU762
MET766LEU788
THR790GLN791
LEU792MET793
GLY796 CYS797
ARG841<\/p>\n

ASN842LEU
844THR854<\/p>\n

ASP855<\/p>\n

Ionic (5),
hydrophobic (7),
weak hydrogen (1),
hydrogen (1)<\/p>\n<\/td>\n

\n

LEU718VAL726LYS
728ALA743LYS745
GLU762MET766
THR790GLN791
LEU792MET793
PRO794PHE795
GLY796CYS797
ASN842LEU844
THR854ASP855<\/p>\n

Ionic (2), hydrogen (5),
hydrophobic (10),
weak hydrogen (2)<\/p>\n<\/td>\n

\n

LEU718GLY719VAL
726ALA743LYS745
GLU762MET766
LEU788THR790GLN
791LEU792MET793
PRO794PHE795GLY
796CYS797LEU844
THR854ASP855<\/p>\n

Ionic (2),
hydrophobic (8),
weak hydrogen (1),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

1DI8<\/p>\n<\/td>\n

\n

ILE10GLY11GLU
12GLY13VAL18
ALA31LYS33VAL
64PHE80GLU81
PHE82LEU83HIS
84GLN85ASP86
GLN131ASN132
LEU134ALA144
ASP145<\/p>\n

Ionic (2),
hydrogen (2),
hydrophobic (19),
weak hydrogen (1)<\/p>\n<\/td>\n

\n

ILE10VAL18ALA
31LYS33VAL64PH
E80GLU81PHE82
LEU83HIS84GLN85
ASP86LYS89GLN131
ASN132LEU134ALA
144ASP145<\/p>\n

Ionic (1)
hydrophobic  (15),
<\/span>weak hydrogen (1),
hydrogen (3)<\/p>\n<\/td>\n

\n

ILE10VAL18ALA31
LYS33VAL6PHE80G
LU81PHE82LEU83H
IS84GLN85ASP86G
LN131LEU134ALA
144ASP145PHE146
LEU148<\/p>\n

Hydrophobic (15),
ionic (1), weak
hydrogen (2),
hydrogen (8) <\/p>\n<\/td>\n<\/tr>\n

\n

3KRR<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU855GLY856
LYS857GLY858
ASN859GLY861
SER862VAL863
LYS882GLY935
SER936ASP939
ARG980ASN981
ILE982LEU983
GLY993ASP994<\/p>\n

Hydrogen (3), 
hydrophobic (10),
weak hydrogen bond (2)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU855GLY856
LYS857GLY858
ASN859GLY861
SER862VAL863
ALA880LYS882
GLU930TYR931
LEU932GLY935S
ER936ARG980AS
N981LEU983ASP994<\/p>\n

Hydrophobic (11),
ionic (1)weak
hydrogen (8),
hydrogen (3)<\/p>\n<\/td>\n

\n

LEU855VAL863ALA
880LYS882VAL911
MET929GLU930TYR
931LEU932PRO933
TYR934GLY935SER
936ASP939LEU983
GLY993ASP994<\/p>\n

Hydrophobic (8),
ionic (1) Weak
hydrogen (3),
hydrogen (8)<\/p>\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

4FA2<\/p>\n<\/td>\n

\n

VAL30VAL38
ALA51VAL52<\/p>\n

LYS53ILE84
LEU104THR106
HIS107LEU108
MET109GLY110
ALA111ASP112
SER154ASN155
ALA157LEU167
PHE169GLY170
LEU171<\/p>\n

Hydrophobic (14),
weak hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

VAL30VAL38ALA51
VAL52LYS53GLU71
LEU75ILE84LEU104
THR106HIS107LEU
108MET109GLY110
ALA111ASP112ASN
115SER154ALA157
LEU167ASP168PHE
169 LEU171<\/p>\n

Ionic (1),
hydrogen(4),
hydrophobic (16),
weak hydrogen (3)<\/p>\n<\/td>\n

\n

VAL30VAL38ALA51
VAL52LYS53GLU71
LEU75ILE84GLY85
LEU86ASP88LEU10
4VAL105THR106GL
Y110ALA111SER154
ASN155LEU167PHE
169GLY170LEU171<\/p>\n

Hydrophobic (14),
ionic (1) weak
hydrogen (3),
hydrogen (6)<\/p>\n<\/td>\n<\/tr>\n

\n

5NKA<\/p>\n<\/td>\n

\n

ILE619VAL627
ALA644LYS646
GLU663MET667
ILE676ILE690
THR692GLU693
TYR694MET695
GLU696GLY698
ALA699ARG743
ASN744 ILE745
LEU746<\/p>\n

SER756ASP757<\/p>\n

Hydrophobic (8),
ionic (1) weak
hydrogen (2),
hydrogen (1)<\/p>\n<\/td>\n

\n

ILE619VAL627ALA
644ILE645LYS646
GLU663ALA664
MET667ILE676ILE
690ILE691THR692
GLU693TYR694MET
695GLY698ALA699
LEU746SER756ASP
757PHE758<\/p>\n

Hydrophobic (13),
hydrogen (6) weak
hydrogen bond (1)<\/p>\n<\/td>\n

\n

ASP708LEU716TRP
808MET811THR812
TYR813GLU815TRP
819PRO837THR838
PRO839MET840PHE
887 ASP888<\/p>\n

Hydrophobic (10),
hydrogen (8),weak
hydrogen (1), pi-pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

3G51<\/p>\n<\/td>\n

\n

LEU74GLY75GLN
76GLY77SER78GLY
80VAL82ALA98
LYS100ASP148
PHE149LEU150
ASP154GLU197
ASN198LEU200
THR210ASP211
LYS216<\/p>\n

Hydrophobic (11),
ionic (2) weak
hydrogen bond (1)<\/p>\n<\/td>\n

\n

LEU74GLY75GLN
76GLY77SER78PHE
79GLY80VAL82LYS
100TYR191ASP193L
YS195GLU197ASN1
98LEU200THR210A
SP211PHE212GLY21
3LEU214LYS216<\/p>\n

Hydrophobic  (9),
hydrogen (7),  ionic (2),
weak hydrogen (5)<\/p>\n<\/td>\n

\n

LEU74GLY75GLN76
GLY77SER78VAL82
ALA98LYS100VAL1
31LEU147ASP148P
HE149LEU150ARG
151LYS195GLU197
ASN198LEU200 THR210<\/p>\n

Hydrophobic (15),
hydrogen(2),  
weak hydrogen (1)<\/p>\n<\/td>\n<\/tr>\n

\n

4KIK<\/p>\n<\/td>\n

\n

ARG105CYS114
GLU214GLY218
PHE219ARG220
PRO224ASN225
PHE424GLN425
ARG427LYS428
TYR571ARG575<\/p>\n

Ionic (2),
cation-pi (1)
hydrophobic (6),
hydrogen (3), 
weak hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

PHE219VAL244SER2
46GLU247ASP248LEU
249LYS254PHE255SER
256SER258LEU259PR
O260TYR261GLU408
SER409PHE424GLN4
25LYS428<\/p>\n

GLN432<\/p>\n

Ionic (1),
hydrophobic (5),
weak hydrogen (3),
hydrogen (4)<\/p>\n

 <\/p>\n<\/td>\n

\n

ARG105LEU108ASN
109CYS114CYS115G
LU214THR217GLY2
18PHE219ARG220PR
O224ASN225ARG42
7LYS428VAL429TRP
430GLY431 GLN432
TYR571<\/p>\n

Ionic (2), hydrophobic (3),
weak hydrogen (6),
hydrogen (10), cation-pi (1) <\/p>\n<\/td>\n<\/tr>\n

\n

3OW4<\/p>\n<\/td>\n

\n

LEU156GLY157
LYS158VAL164
ALA177 LYS179
GLU198THR21
MET227GLU228
TYR229ALA230
GLU234ASN279
MET281THR291
ASP292 PHE438ARG4<\/p>\n

Ionic (7), pi-pi (1)
hydrophobic (7),
weak hydrogen (4),
hydrogen(3),
cation-pi (1)<\/p>\n<\/td>\n

\n

LEU156GLY157VAL
164ALA177LYS179
GLU198MET227A
LA230GLY233GLU
234PHE236PHE237
ARG241MET281THR
291ASP292TYR437
PHE438ASP439PHE
442ARG4<\/p>\n

Ionic (2),
hydrogen (7)
hydrophobic (9),
weak hydrogen (1)<\/p>\n<\/td>\n

\n

LEU156GLY157LYS
158VAL164ALA177
LYS179MET227GLU
228ALA230GLU234
PHE237MET281THR
291TYR437PHE438A
SP439PHE442ARG4<\/p>\n

Ionic (1),
hydrophobic (10),
weak hydrogen (3),
hydrogen (3)<\/p>\n<\/td>\n<\/tr>\n

\n

4M4P<\/p>\n<\/td>\n

\n

ILE336SER337
ASN338ASN345
LEU346GLU347
LYS397VAL398
GLU475ARG514
ALA519GLY
520TYR521<\/p>\n

Hydrophobic (3),
weak hydrogen (1),
Ionic (5),
pi-pi sticking (1),
cation-pi (1)<\/p>\n<\/td>\n

\n

GLU451THR453TYR
455SER456ALA458A
SP499LYS501GLY502
PRO536SER537ARG5
38ILE539ILE540<\/p>\n

Hydrophobic (7),
weak hydrogen (5),
hydrogen (7), ionic (2)<\/p>\n<\/td>\n

\n

ARG37SER38GLN40
ASP61LYS63ASN6
4THR65PRO66ILE67
ASP158ILE159GLY160
ASP161<\/p>\n

Ionic (2) hydrophobic 
(2),weak hydrogen (3),
hydrogen (9)<\/p>\n<\/td>\n<\/tr>\n

\n

6NJZ<\/p>\n<\/td>\n

\n

TRP43LEU44
THR45TYR48
TRP52ASP53
LEU54TYR67
THR132LEU
44THR45HIS
46TYR48THR
132PHE134<\/p>\n

Pi-pi (1),
hydrophobic (6),
weak hydrogen (4),
hydrogen (3),
ionic (2)<\/p>\n<\/td>\n

\n

GLY39GLU40LEU41
GLY42TRP43LEU44
THR45TYR48LEU54T
YR67TYR48THR132<\/p>\n

ASN133MET10<\/p>\n

Hydrophobic (7),
hydrogen (11) weak
hydrogen(1)<\/p>\n<\/td>\n

\n

TRP43LEU44THR45
HIS46TYR48TYR67
THR132TRP43LEU44
THR45 TYR48THR132<\/p>\n

Pi-pi (1), hydrophobic 
(8), weak hydrogen (3),
hydrogen (5)<\/p>\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

2A5U<\/p>\n<\/td>\n

\n

LEU657HIS658
LEU661ARG690
PHE694PHE698
TYR787ASP788
MET842LEU843
LEU845GLN846
ARG849PRO866
TYR867GLY868
CYS869ILE870
GLU880<\/p>\n

Hydrophobic (12),
cation-pi (2),
weak hydrogen (2),
hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

TRP201PRO208TYR
210LEU211GLN291
ARG294HIS295LYS
298ASP654LEU657
HIS658LEU660ARG
690PHE694PHE698
ARG849GLU852SER
853GLU856<\/p>\n

Hydrophobic (18),
hydrogen (6), i
onic (3), cation-pi (1)<\/p>\n

 <\/p>\n<\/td>\n

\n

MET804PRO810TRP
812ILE831LYS833AS
P836LEU838ASP841
TYR867ILE879GLU
880ILE881VAL882L
YS883ALA885THR8
86THR887MET953P
HE961ILE963ASP964
PHE965<\/p>\n

Hydrophobic (18),
weak hydrogen (5),
hydrogen (4),
ionic (2), cation-pi (2)<\/p>\n<\/td>\n<\/tr>\n

\n

2J6M<\/p>\n<\/td>\n

\n

LEU718PHE723
VAL726ALA743
LYS745GLU762
MET766LEU788
THR790GLN791
LEU792MET793
GLY796CYS797
ARG841ASN842
LEU844THR854
ASP855<\/p>\n

Ionic (5),
hydrophobic (7),
weak hydrogen (1),
hydrogen(1)<\/p>\n<\/td>\n

\n

LEU718VAL726LYS728
ALA743LYS745GLU762
MET766THR790GLN791
LEU792MET793PRO794
PHE795GLY796CYS797
ASN842LEU844THR854
ASP855<\/p>\n

Ionic (2),
hydrophobic (10),
weak hydrogen (2),
hydrogen (5)<\/p>\n<\/td>\n

\n

LEU718GLY719VAL
726ALA743LYS745G
LU762MET766LEU7
88THR790GLN791L
EU792MET793PRO7
94PHE795GLY796CY
S797LEU844 THR85
4ASP855<\/p>\n

Ionic (2),
hydrophobic (8),
weak hydrogen (1),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

2OH4<\/p>\n<\/td>\n

\n

ASP1026ARG1030
ASN1031ASP1044
PHE1045GLY1046
LEU1047ALA1048
ARG1049ASP1050
ILE1051ASP1062
ALA1063 ARG1064
PRO1066<\/p>\n

Ionic (4),
hydrophobic (3),
weak hydrogen (4),
hydrogen (5),
cation-pi (1)<\/p>\n<\/td>\n

\n

ASP1026ARG1030
ASN1031CYS1043
ASP1044PHE1045
GLY1046LEU1047
ALA1048ARG1049
ASP1050ILE1051A
LA1063ARG1064LE
U1065<\/p>\n

PRO1066<\/p>\n

Ionic (2),
hydrophobic (6),
cation-pi (1),
weak hydrogen (2),
hydrogen (9)<\/p>\n<\/td>\n

\n

ASP1026ARG1030A
SN1031ASP1044PH
E1045GLY1046ALA
1048ARG1049ASP10
50ILE1051ARG1064
LEU1065 PRO1066<\/p>\n

Ionic (1), hydrophobic (15),
weak hydrogen (2),
hydrogen bonds (8),
cation – pi (1)<\/p>\n<\/td>\n<\/tr>\n

\n

3CQU<\/p>\n<\/td>\n

\n

LEU156GLY157
LYS158PHE161
VAL164ALA177LYS
179GLU198THR211
MET227GLU228TYR
229ALA230GLY233
GLU234GLU278MET
281THR291ASP292
PHE438<\/p>\n

Ionic (3),
hydrophobic (14),
weak hydrogen (3),
hydrogen (5)<\/p>\n

 <\/p>\n<\/td>\n

\n

THR160LYS179
LEU181ILE186
LYS189GLU191
HIS194THR195
GLU198ASP274
ASP292GLY294
LEU295THR6S
ER7PHE8ALA9
GLU10<\/p>\n

Ionic (2),
hydrophobic (16),
weak hydrogen (11),
hydrogen (16) <\/p>\n

 <\/p>\n<\/td>\n

\n

LEU156GLY157LYS1
58PHE161VAL164A
LA177LYS179THR21
1MET227GLU228TYR
229ALA230ASN231G
LU234GLU278ASN279
MET281THR291ASP29
2PHE438PHE442 ARG4<\/p>\n

Ionic  (2),
hydrophobic (13),
weak hydrogen (6),
hydrogen (9)<\/p>\n<\/td>\n<\/tr>\n

\n

5FED<\/p>\n<\/td>\n

\n

LEU718GLY719
VAL726ALA743
LYS745GLU762
MET766CYS775
LEU788THR790
GLN791MET793
GLY796CYS797
ARG841ASN842
LEU844THR854
ASP855<\/p>\n

Ionic (1),
hydrophobic (9),
weak hydrogen (1),
hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU718VAL726
LYS728ALA743
LYS745CYS775
THR790GLN791
LEU792MET793
PRO794PHE795
GLY796CYS797
ARG841ASN842
LEU844THR854<\/p>\n

Ionic (1),
hydrophobic (12),
weak hydrogen (3),
hydrogen (5)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU718GLY719VAL
726ALA743ILE744L
YS745GLU762MET7
66CYS775LEU788ILE
789THR790LEU792MET
793PRO794PHE795GLY7
96CYS797ARG841LEU
844THR854 ASP855<\/p>\n

Hydrophobic (9),
ionic (1) weak
hydrogen (5),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

2A2R<\/p>\n<\/td>\n

\n

TYR7PHE8VAL10
GLY12ARG13GLN
51ILE104TYR108
ILE203ASN204
GLY205ASN206<\/p>\n

Hydrophobic
(13), pi-pi  (1)
weak hydrogen (1),
hydrogen (4)<\/p>\n

 <\/p>\n<\/td>\n

\n

ARG13GLN51LEU
52PRO53GLN64S
ER65ASN66ASP9
4GLU97CYS101I
LE104ChainB:AS
N66ARG70ASP94
GLU97ASP98<\/p>\n

Ionic (2),
hydrophobic (6),
weak hydrogen (4),
hydrogen (9)<\/span><\/p>\n<\/td>\n

\n

ARG74TYR79GLY80
LYS81ASP82GLN83
ALA86ChainB:GLY73
ARG74GLY77LEU78
TYR79GLY80LYS81
ASP82GLN83ALA86<\/p>\n

Ionic (2),
hydrophobic (7),
weak hydrogen (2),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

3OCB<\/p>\n<\/td>\n

\n

GLY159THR160
PHE161GLY162
LYS163VAL164
LYS179LEU181
ILE186GLU191
HIS194THR195
GLU198PHE225
TYR272ASP274
ASN279ASP292
PHE293GLY294
LEU295SER7<\/p>\n

Ionic (5),
hydrophobic (8),
weak hydrogen (3),
hydrogen (11), 
cation-pi (1)<\/p>\n<\/td>\n

\n

LYS158GLY159PHE
161LYS179LEU181I
LE186GLU191HIS19
4THR195GLU198AS
P274LYS276GLU278
ASN279ASP292GLY2
94ARG4THR5THR6SER7<\/p>\n

Ionic (4),
hydrophobic (9),
weak hydrogen (3),
hydrogen (13)<\/p>\n<\/td>\n

\n

LEU156GLY157LYS
158GLY159VAL164
ALA177LYS179THR
211MET227GLU228
TYR229ALA230ASN
231GLU234MET281
THR291ASP292PHE
438PHE442ARG4<\/p>\n

Ionic (2),
hydrophobic (13),
weak hydrogen (1),
hydrogen (7)<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

3O96<\/p>\n<\/td>\n

\n

ASN53GLN79TRP
80THR81THR82VAL
201SER205LEU210
THR211LEU264LYS
268VAL270VAL271
TYR272ILE290ASP292<\/p>\n

Ionic (1),
pi-pi (1),
hydrogen (2)
hydrophobic (13),
weak hydrogen (1),<\/p>\n

 <\/p>\n<\/td>\n

\n

ASN54GLN79TRP80THR81
THR82VAL83ILE84ARG86L
YS179VAL270VAL271TYR27
2ARG273ASP274ASP292GLY
294TYR326<\/p>\n

Hydrophobic (11),
hydrogen (9) weak
hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

ASN54GLN79TRP80
SER205ARG206HIS
207LEU210THR211
ALA212TYR263LEU
264LYS268VAL270V
AL271TYR272ARG2
73ILE290 THR291ASP292<\/p>\n

Hydrophobic (9),
pi-pi (1)  weak
hydrogen (4),
hydrogen (9)<\/p>\n<\/td>\n<\/tr>\n

\n

3PP0<\/p>\n<\/td>\n

\n

LEU726VAL734
ALA751ILE752
LYS753SER783
LEU796THR798
GLN799LEU800
MET801GLY804
CYS805ARG849
ASN850LEU852
THR862ASP863
PHE1004<\/p>\n

Ionic (1),
hydrophobic (9),
hydrogen (3),
weak hydrogen (3)<\/p>\n

 <\/p>\n<\/td>\n

\n

LEU726GLY727S
ER728GLY729VAL
734ALA751ILE752
LYS753GLU770MET
774SER783LEU785L
EU796THR798LEU80
0GLY804CYS805ASP80
8ARG849ASN850LEU85
2THR862ASP863PHE864<\/p>\n

Ionic (1),
hydrophobic (12),
<\/span>weak hydrogen (3),
hydrogen (5)<\/span><\/p>\n<\/td>\n

\n

LEU726SER728GLY
729ALA730VAL734
ALA751ILE752LYS7
53SER783LEU785LE
U796VAL797THR79
8LEU800MET801GL
Y804CYS805ARG849
ASN850LEU852THR
862ASP863<\/p>\n

Ionic (1),
hydrophobic (11),
weak hydrogen (3),
hydrogen (7)<\/p>\n<\/td>\n<\/tr>\n

\n

3OAW<\/p>\n<\/td>\n

\n

TRP201LEU
657HIS658<\/p>\n

LEU661ARG690
PHE694PHE698
TYR787ASP788
ME842LEU845
GLN846ARG849
PRO86TYR867
GLY868CYS869
ILE870<\/p>\n

GLU880<\/p>\n

Ionic (1),
cation-pi (3),
hydrophobic (12),
hydrogen (4),
weak (3)<\/p>\n<\/td>\n

\n

SER806LYS807LYS808
ILE831LYS833ASP836
ASP841TYR867ILE879
ASP950ASN951MET95
3ILE963ASP964HIS967
LEU1090<\/p>\n

Pi-pi (2),
hydrophobic (11)<\/span><\/p>\n

 <\/p>\n<\/td>\n

\n

ALA889LYS890GLN
892GLN893ASN898
THR899PHE902HIS
948ASN949ASP950
GLN1083PHE1084
TRP1086PHE1087
LEU1090VAL1091<\/p>\n

Pi-pi (3),
hydrophobic (10),
<\/span>hydrogen (4)<\/p>\n<\/td>\n<\/tr>\n

\n

3CQW<\/p>\n<\/td>\n

\n

LYS158GLY159
THR160PHE161
GLY162LYS163
VAL164LYS179
LEU181GLU191
HIS194GLU198
ASP274LYS276
GLU278ASN279
ASP292PHE293
GLY294LEU295
ARG4THR5THR
6SER7<\/p>\n

Ionic (5), weak (3),
hydrophobic (6),
hydrogen (7)<\/p>\n<\/td>\n

\n

LYS158GLY159P
HE161GLY162LYS
179LEU181ILE186
GLU191HIS194THR
195GLU198ASP274LY
S276GLU278ASN279A
SP292GLY294LEU295T
HR312ARG4THR5THR6 SER7<\/p>\n

Hydrophobic (12), hydrogen (18), ionic (5), weak (4)<\/p>\n<\/td>\n

\n

LEU156GLY157
LYS158GLY159V
AL164ALA177LY
S179THR211MET
227GLU228TYR22
9ALA230ASN231G
LU234GLU278ASN
279MET281THR291
ASP292PHE438PHE442<\/p>\n

ARG4<\/p>\n

Weak (3),
hydrophobic (11),
ionic (2)<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 12: A. Binding patterns of breast cancer transferases with drugs.<\/strong><\/p>\n

 <\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 12: B. Binding patterns of breast cancer transferases with drugs.<\/strong><\/p>\n

 <\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

The\nEphA4 receptor, (Eph receptor tyrosine kinases family member), is a well-known\ncell functions (cell adhesion, invasion and migration) regulator. These events\noccur due to modification of actin cytoskeleton organization. In a variety of\ncell types, FKBP1 is identified as NF-\u03baB signaling regulator (nuclear factor\nbinding near the \u03ba light-chain in B-cells). As a result, FKBP51 is proposed as\na target to treat NF-\u03baB-mediated inflammation and cancer. Cancer relies heavily\non p38 activity. p38 mitogen-activated protein kinases (MAPKs) are important in\ncancer cellular responses, proliferation, survival, cell cycle and migration.\nThe growth factor-activated Ser\/Thr kinase p90 ribosomal protein kinase 2\n(RSK2) is involved in cell multiplication and tumor promoter-induced cell\ntransformation. Cell growth, motility, survival, metabolism, and angiogenesis\nare all regulated by human PI3K gamma.\nCDKs (Cyclin-dependent kinases) play critical role\nin cell cycle progress and RNA transcription.\nGSTP-silencing effectively suppressed cell proliferation while not completely\nkilling the cells. GSTP performs a non-enzyme function in signal transduction\nvia a protein-protein interaction with JNK that guards cancer cells from\napoptosis. AKT1 kinase (AKT kinase – a serine\/threonine-protein kinase) regulates\nmany signaling downstream pathways participate in cell proliferation,\nmetabolism, survival, growth, and angiogenesis. It belongs to the most commonly\ntriggered multiplying and surviving pathways in cancer. Autophagy and\nmetabolism are both regulated by EGFR. Non-canonical functions are commonly\nbrought by cellular and environmental stresses. These \u2018stress pathways\u2019 are\nactivated in cancer cells and benefit them to survive and resist to therapy. Human IkB kinase beta (IkappaB\nkinase or IKK) is involved cell proliferation regulation, apoptosis control,\nangiogenesis promotion and invasion\/metastasis stimulation. EGFR regulates EMT\n(epithelial-mesenchymal transition), cell migration and invasion. Its high\nexpression is a sole predictor of poor diagnosis in Inflammatory Breast Cancer\n(IBC) and by rewiring apoptotic signaling networks in Triple Negative Breast\nCancer (TNBC), its inhibition improves chemosensitivity20<\/sup>. <\/p>\n\n\n\n

Upregulation\nof intra-cellular signaling paths, PI3K\/Akt\/mTOR pathway, considering an\nexample, promotes cancer growth and development by driving cellular\nproliferation, resulting in un-checked cell growth. VEGFR-2 regulates tumor\nangiogenesis directly. The VEGF\/VEGFR-2 system is essential for cancer cell\ndivision and survival as an autocrine\/paracrine process. Breast cancers\noverexpress the HER2 receptor, and HER2 overexpression is linked to aggressive\ntumor growth and metastasis. Cyclin-dependent\nkinase 6 (CDK6) is vital in cell cycle progression regulation. Recently, it was\nshown that CDK6 plays a transcriptional lead in tumor angiogenesis. NMPRTases\nare important in the salvage pathway of NAD+ biosynthesis. FK866 (a potent\nNMPRTase inhibitor) reduces cellular NAD+ levels and induces apoptosis in\ntumors. The MAPK signaling pathway connects extracellular signals to\nthe intracellular process that regulates growth, proliferation, migration, and\napoptosis20<\/sup>. <\/p>\n\n\n\n

Docking\nsimplified the analysis of protein-ligand interactions. Hydrogen, weak\nhydrogen, hydrophobic, ionic, pi-pi sticking, covalent, and van der Waals\ninteractions are examples of interactions23<\/sup>. The study highlights\nthe main bond pattern viz.,<\/em> hydrogen,\nhydrophobic, in addition to weak hydrogen bonds and limited cation-pi, pi-pi\nsticking, and ionic interactions. These bonds have a significant correlation\nwith the vina score of the respective drug and its counterpart ligand.\nFurthermore, the energies were high due to the increased hydrogen and\nhydrophobic interactions. <\/p>\n\n\n\n

Among the\ntransferase target classes investigated in this\nstudy, cyclin-dependent kinase had the highest vina score with quercetin when\ncompared to the other two drugs. The first higher class is (1XO2), which is\nfollowed by (1DI8), which has more hydrogen and hydrophobic bonds, considered\nas predominant in this class. Chronic inflammation is distinguished by the\nproduction of reactive nitrogen and oxygen species. These species initiate\ntumorigenesis, inhibit apoptosis, promote hyper cellular proliferation, and\npromote angiogenesis. These conditions cause the NFkB pathways to be activated.\nAlthough NFkB is required for normal mammary cell morphogenesis, irregular\nexpression has been observed in BC cells24<\/sup>. A good idea is to target\nNFkB to control cell proliferation. The molecules studied were (1NFK), but with\na vina score of -9.6, quercetin came out on top. The mitogen-activated protein kinase (MAPK) pathway regulates several\nprocesses including tumor development. In conjugation with the MAPK cascade,\nbeta-arrestin proteins target G protein-couple receptors and promote tumor\nprogression25<\/sup>. Targeting\nbeta-arrestin is a good choice, and in this study, quercetin effectively\ntargeted (6K3F) beta-arrestins. Estrogen receptors aid in the binding of\nestrogen, which is required for cell proliferation, and blocking these\nreceptors aids in the supervision of cancer disease. Again quercetin has a\nstrong affinity for the estrogen receptor (4PP6). <\/p>\n\n\n\n

In\ncancer prevention, redox maintenance in cell is critical. In aerobic\nconditions, ROS (reactive oxygen species) influence lipid, protein and DNA metabolism\nand function. Changes in DNA and proteins are important in cancer\npathophysiology. Oxidoreductases are the enzymes that maintain ROS and\nneutralize oxidative stress26<\/sup>.<\/em>\nChemoresistance is linked to Prostaglandin G\/H synthase 2 and is linked to\ninjury, proliferation, and inflammation 27<\/sup>,28<\/sup>. The\nCytochrome P450 1A1\/ A2 (CYP1A1\/A2) enzyme metabolizes both xenobiotics and\nendogenous substrates. These enzymes are involved in the activation of\npro-carcinogens (estradiol and polycyclic aromatic hydrocarbons)29<\/sup>.<\/p>\n\n\n\n

The\ntargeted proteins (3LN1, 6DWN and 2HI4) bound to quercetin with a highest vina\nscore than the other two drugs. The alpha enzyme, DNA topoisomerase II, changes\nthe topology of DNA during transcription. The enzyme primarily catalyzes the\ntemporary breaking (transient) and rejoining of the two duplex DNA strands,\nthere by altering the topology30<\/sup>. With the highest vina score of the\nthree drug molecules, Quercetin targeted this enzyme.  Matrix metalloproteinase-9 degrades\nextracellular matrix proteins, and surface plasma proteins, allowing them to be\nreleased to the cell surface. It plays a wide range of roles in invasion,\nangiogenesis, and metastasis. Targeting MMP-9 is the best option, and present\nwork highlighted that quercetin was the best at it. Myeloid cell leukemia-1, a\nclose relative of B-cell lymphoma 2, promotes survival and invasion of cancer\ncells, making it an important chemotherapeutic target. The highest vina score\nof (-8.5) was achieved by quercetin.<\/p>\n\n\n\n

The\nstudy concluded that cancer metabolism is largely reliant on amino acids, which\nare aided by the TCA cycle. Amino acid derivatives promote cancer cell\nprogression and improve cells\u2019 ability to metastasize. Amino acid\ncatabolism (metabolic intermediates) influences the survival and growth of cancer\ncells. Targeting the enzymes with the amino\nacids such as leucine, valine, and glutamine (TCA cycle fuel); asparagine,\nglycine, and glutamine (nucleotide biosynthesis); serine, methionine, glycine\n(methionine-folate cycle); glutathione, cysteine, and glycine (to\nmaintain redox balance); methionine, serine, and glycine (DNA and histone\nmethylation) reduces the cancer cell proliferation and tumor burden31<\/sup>.\nMore vina score correlates with more hydrogen\nand hydrophobic interactions.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

It confirms that, out of the three drugs tested, the natural compound quercetin establishes the most effective in targeting and controlling the BC cells, in line with our in vitro<\/em> work10<\/sup>.  When BC cell lines were fed with quercetin, anastrozole, and capecitabine, both independently and in combination, a decrease in cell viability and increase in apoptosis percentage at low doses of Quercetin10 <\/sup>was noted. Because quercetin is chemoprotective and radioprotective to healthy\/normal cells, it can be used during cancer treatment.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

Author is grateful to the Academy, Sri Devaraj Urs Acadmy of Higher Education and Research for providing the facility to carry out this docking study. Author is mentioning her gratitude to Dr. Prashanthi K., Assistant Professor, Department of Biotechnology, M.S. Ramaiah University of Applied Sciences, Bengaluru.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

There is no conflict of interest.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

There is no funding Sources.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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