{"id":33870,"date":"2020-06-25T11:36:35","date_gmt":"2020-06-25T11:36:35","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=33870"},"modified":"2020-07-06T09:42:51","modified_gmt":"2020-07-06T09:42:51","slug":"development-of-trimethoprim-drug-and-innovation-of-sulfazane-trimethoprim-derivatives-as-anticancer-agents","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol13no2\/development-of-trimethoprim-drug-and-innovation-of-sulfazane-trimethoprim-derivatives-as-anticancer-agents\/","title":{"rendered":"Development of Trimethoprim Drug and Innovation of Sulfazane-Trimethoprim Derivatives as Anticancer Agents"},"content":{"rendered":"

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

The newly\u00a0 innovative\u00a0 sulfazane\u00a0 compounds\u00a0 that\u00a0 were\u00a0 invented\u00a0 and\u00a0 prepared\u00a0 for the first\u00a0 time\u00a0 by the researcher (Dr. Nagham Aljamali in year 2019\u00a0 in the first research work(1)<\/sup>) The researcher laid the first foundations for the innovative sulfazane compounds in terms of (methods of preparation , their properties , chemical and physical characteristics, their colors, stability, some of their vital applications and behavior towards some types of bacteria and fungi).(1,2) <\/sup>Now in this research work continued to prepare other drug derivatives by linking sulfazane to the drug trimethoprim via (-S-N=N-) sulfazane\u00a0 group to study its effect on cancerous tumors.Trimethoprim contains the active ingredient trimethoprim, an antibiotic used to treat infections with bacteria.Bacterial cells in order to grow and multiply need a genetic material (DNA) to produce DNA and need folic acid (folate).(3-10) <\/sup>Methoprim works by preventing bacteria from producing folic acid and without it bacteria cannot produce DNA, and thus become unable to reproduce(11-22)<\/sup> and increase numbers, so methoprim stops the spread of infection, and kills the remaining bacteria by the immune system.(23-34)<\/sup><\/p>\n

\"Vol13No2_Dev_Nag_Img1\"<\/p>\n

Trimethoprim (C14H18N4O3) : 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine., its\u00a0 names (Proloprim, Monotrim, Triprim, others) ,M.Wt : 290.32 g\/mol .,It is used to treat bacterial infections in the urinary tract and also to prevent frequent bacterial infections in the urinary tract,(35-43)<\/sup> as well as to treat bacterial infections in the lungs and bronchi (respiratory system), such as acute bronchitis, chronic bronchitis or pneumonia.(44-56)\u00a0<\/sup>The cancer\u00a0 is a type of non-infectious disease that is characterized by uncontrolled growth of cells, there are more than (100) different types of cancer, which were classified according to the type of cell that was affected at the beginning, and cancer causes a death rate of more than 20% of the total deaths in the world on according to the World Health Organization, where lung cancer is the most prevalent,(57-59)<\/sup> followed by breast, colon and prostate cancer, despite significant progress in cancer treatment, the death rate has not decreased, so it has become necessary to understand the molecular explanations that contribute to the development and progress of cancer and search for more treatments. Efficacy and least toxic for a processor with this disease,(60-63)<\/sup> there are many methods for treating this disease, including tumor lift, multiple chemical treatments, and radiological treatments<\/p>\n

Experimental\u00a0 Part <\/strong><\/p>\n

All chemicals compounds supplied from Sigma \u2013chemicals company and fluka \u2013chemicals company.<\/p>\n

An innovative method(1, 2)<\/sup> was used to develop the trimethoprim drug by linking it to an innovative sulfazane compounds through several steps, chemical reactions and reaction conditions that differ for each of the innovative derivatives prepared in this research. The chemical composition of the innovative derivatives prepared in this research was proven by several\u00a0 investigation techniques (FT-IR spectra (FT-IR 8300 Shimadzu) with the range (400-4000)cm-1<\/sup>\u00a0 using discs of\u00a0 KBr., 1H.NMR\u2013Spectra in\u00a0 solvent (d-DMSO) Fourier transformation broker spectrometer ,operating at (400MHz)., HMBC- Spectrum ,Mass spectra for some of them) in Kashan university, and the preparation was followed by (TLC), then a laboratory study of cancer cells line to know the effectiveness and efficiency of\u00a0 the innovative compounds.<\/p>\n

Paths\u00a0 of\u00a0 Synthesis(1, 2)<\/sup><\/strong><\/p>\n

Innovation and Creation of Sulfazane- Trimethoprim {1}<\/strong><\/p>\n

P-thiol aniline (0.01 mole) with (0.01 mole) ammonium thiocyanate in bromine with glacial acetic acid ,after rotation for (2 hrs) at (10 C\u00b0) via three reactions ,then precipitation filtered, washed, dried, purification by recrystallization, then (0.01 mole) from precipitation dissolved in basic alcoholic solution, and added\u00a0 to\u00a0 acidic diazo- trimethoprim salt in three steps according to invented\u00a0 procedure in papers(1, 2) <\/sup>,after (3 days), filtered ,washed ,dried ,recrystallized to yield\u00a0 sulfazane- trimethoprim {1}.<\/p>\n\n\n\n
\"Scheme.1:<\/td>\nScheme 1: Creation of Sulfazane- Trimethoprim {1}<\/strong><\/p>\n

Click here to View Scheme<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Innovation and Creation of Sulfazane- Trimethoprim {2}<\/strong><\/p>\n

Cystein(0.01 mole) in basic alcoholic solution by two steps, then added\u00a0 to acidic diazo- trimethoprim salt in three steps according to invented\u00a0 procedure in papers(1, 2) <\/sup>,after (3 days), filtered ,washed ,dried ,recrystallized to yield\u00a0 sulfazane- trimethoprim {2}.<\/p>\n\n\n\n
\"Scheme.2:<\/td>\nScheme 2: Creation of Sulfazane- Trimethoprim {2}<\/strong><\/p>\n

Click here to View Scheme<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Innovation and Creation of Sulfazane- Trimethoprim {3}<\/strong><\/p>\n

Thiol benzoic acid (0.01 mole) in basic alcoholic solution by two steps, then added\u00a0 to acidic diazo- trimethoprim salt in three steps according to invented\u00a0 procedure in papers(1, 2) <\/sup>, after (3 days), filtered ,washed ,dried ,recrystallized to yield\u00a0 sulfazane- trimethoprim {3}.<\/p>\n\n\n\n
\"Scheme.3:<\/td>\nScheme 3: Creation of Sulfazane-Trimethoprim {3}<\/strong><\/p>\n

Click here to View Scheme<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Innovation and Creation of Sulfazane- Trimethoprim {4}<\/strong><\/p>\n

2-Thiol imidazole in previously steps was prepared ,then (0.01 mole) dissolved in basic alcoholic solution by two steps, then added to acidic diazo-trimethoprim salt in three steps according to invented procedure in papers(1, 2) <\/sup>, after (3 days), filtered ,washed ,dried ,recrystallized to yield\u00a0 sulfazane- trimethoprim {4}.<\/p>\n\n\n\n
\"Scheme.4:<\/td>\nScheme 4: Creation of Sulfazane-Trimethoprim {4}<\/strong><\/p>\n

Click here to View Scheme<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

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

Our research described\u00a0 invented\u00a0 procedure(1, 2)<\/sup>\u00a0 via\u00a0 original\u00a0 process to\u00a0 creation and preparation of\u00a0 Sulfazane\u00a0 compounds linked with trimethoprim drug via designation of reaction conditions, type of\u00a0 used catalyst, mechanism\u00a0 of this\u00a0 reaction, we called it (Name\u2013Sulfazane) as a first and Original preparation to this\u00a0 novel type of trimethoprim- derivatives., then all these\u00a0 drug derivatives\u00a0 investigated via numerous spectral techniques and other\u00a0 chemical with physical studies :<\/strong><\/p>\n

Spectral\u00a0\u00a0 Evidences <\/strong><\/p>\n

FT.IR- Spectra<\/strong><\/p>\n

The infrared spectrum is the first technique that has demonstrated, with certain evidence, the creation of innovative, advanced derivatives in this study through the emergence of effective and functional grouping frequencies in derivatives indicating the reason for the accuracy of their preparation and the correctness of the innovative procedure to prepare them :<\/p>\n

Sulfazane- Trimethoprim {1}<\/strong><\/p>\n

Bands at (-OCH3<\/sub>) methoxy group: 1183 ,(-N=N-S-) Azo-Sulfide:<\/strong> (1398, 1489, 1500) , (S-CH-) Sulfide : 1226 ,(C-S) endocyle of benzothiazole : 756 ,(C=N) endocycle of pyrimidine: 1652 ,(-NH2<\/sub>) amine group: (3358 ,3409).<\/p>\n

Sulfazane- Trimethoprim {2}<\/strong><\/p>\n

Bands at (-OCH3<\/sub>) methoxy group: 1118 ,(-N=N-S-) Azo-Sulfide:<\/strong> (1363, 1454, 1496) , (S-CH2<\/sub>-) Sulfide : 1224 , (C=N) endocycle of pyrimidine: 1664 ,(-NH2<\/sub>) amine group: (3314 ,3379), (CO-O-)carbonyl of carboxyl : 1729 .<\/p>\n

Sulfazane- Trimethoprim {3}<\/strong><\/p>\n

Bands at (-OCH3<\/sub>) methoxy group: 1134 ,(-N=N-S-) Azo-Sulfide:<\/strong> (1377, 1462, 1499) , (S-CH-) Sulfide : 1231 , (C=N) endocycle of pyrimidine: 1651 ,(CO-O-)carbonyl of carboxyl : 1721 .<\/p>\n

Sulfazane- Trimethoprim {4}<\/strong><\/p>\n

Bands at (-OCH3<\/sub>) methoxy group: 1130 ,(-N=N-S-) Azo-Sulfide:<\/strong> (1382, 1460, 1502) , , (C=N) endocycle of pyrimidine: 1657 ,(NH) in\u00a0 imidazole : 3210 ,(C=N) endocycle of imidazole: 1632. Other active groups\u00a0 are shown in some selected\u00a0 spectra (1 , 2) .<\/p>\n\n\n\n
\"Figure<\/td>\nFigure 1: I.R Spectrum of Invented Sulfazane-Trimethoprim{1}<\/strong><\/p>\n

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 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 2: I.R Spectrum of\u00a0 Invented Sulfazane-Trimethoprim {2}<\/strong><\/p>\n

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 <\/p>\n

1<\/sup><\/strong>H.NMR- Spectra<\/strong><\/p>\n

The nuclear resonance spectrum is the\u00a0 second technique that has demonstrated, with certain evidence, the creation of innovative, advanced derivatives in this study through the emergence of effective and functional grouping frequencies in derivatives indicating the reason for the accuracy of their preparation and the correctness of the innovative procedure to prepare them \u00a0by disappearance of\u00a0 amine signal of (-NH2<\/sub>) as a result of\u00a0 formation of (sulfazane)- group(1, 2)<\/sup> in\u00a0 derivatives ,<\/strong>all spectra\u00a0 showed signals at (2. 50) for\u00a0 solvent (d-DMSO) ,besides to other\u00a0 signals like:<\/p>\n

Sulfazane- Trimethoprem{1}<\/strong><\/p>\n

It\u00a0 gave signals\u00a0 at (5. 40) due to proton\u00a0 of amine group (NH2<\/sub>) .,(6. 78\u20137. 74) to protons of aromatic ring ,(2. 98) for (O-CH3<\/sub>) protons of\u00a0 methoxy\u00a0 groups.<\/p>\n

Sulfazane- Trimethoprem{2}<\/strong><\/p>\n

It\u00a0 gave signals\u00a0 at (5. 11) due to proton\u00a0 of amine group (NH2<\/sub>) .,(6. 36\u20137. 42) to protons of aromatic ring ,(2. 94) for (O-CH3<\/sub>) protons of\u00a0 methoxy\u00a0 groups ,(COOH) proton of carboxyl group : (13. 26) , (S-CH2<\/sub>-CH-N-): (3. 56 , 3. 76 ).<\/p>\n

Sulfazane- Trimethoprem{3}<\/strong><\/p>\n

It\u00a0 gave signals\u00a0 at (6. 77\u20137. 57) to protons of aromatic ring ,(2. 86) for (O-CH3<\/sub>) protons of\u00a0 methoxy\u00a0 groups ,(COOH) proton of carboxyl group : (13. 08) .<\/p>\n

Sulfazane- Trimethoprem{4}<\/strong><\/p>\n

It\u00a0 gave signals\u00a0 at (6. 69\u20137. 52) to protons of aromatic ring ,(2. 92) for (O-CH3<\/sub>) protons of\u00a0 methoxy\u00a0 groups ,(NH) proton of amine in\u00a0 imidazole ring: (8. 14) . Other\u00a0 protons\u00a0 of\u00a0 functional groups\u00a0 appeared\u00a0 in some spectra (3 , 4) .<\/p>\n\n\n\n
\"Figure<\/td>\nFigure 3: H.NMR-Spectrum of Invented Sulfazane-Trimethoprim {1}<\/strong><\/span><\/p>\n

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 <\/p>\n\n\n\n
\"Figure<\/td>\n\u00a0Figure 4: H.NMR-Spectrum of Invented Sulfazane-Trimethoprim { 2}<\/strong><\/span><\/p>\n

Click here to View Figure<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

HMBC- Spectrum<\/strong><\/p>\n

The\u00a0 HMBC- spectrum is the\u00a0 third\u00a0 technique that has demonstrated, with certain evidence, the creation of innovative, advanced derivatives in this study through the emergence of effective and functional grouping frequencies in derivatives indicating the reason for the accuracy of their preparation and the correctness of the innovative procedure to prepare them via appearance of\u00a0 functional\u00a0 groups for\u00a0 invented derivative, Figures (5).<\/p>\n\n\n\n
\"Vol13No2_Dev_Nag_Fig5\"<\/td>\nFigure 5:<\/strong> HMBC<\/strong> -Spectrum of Invented Sulfazane-Trimethoprim { 2}<\/strong><\/p>\n

Click here to View Figure<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Mass\u00a0 Spectra of\u00a0 Sulfazane \u2013Trimethoprim Derivatives<\/strong><\/p>\n

The\u00a0 mass spectrum is the\u00a0 fourth\u00a0 technique that has demonstrated, with certain evidence, the creation of innovative, advanced derivatives in this study through the emergence of effective and functional grouping frequencies in derivatives indicating the reason for the accuracy of their preparation and the correctness of the innovative procedure to prepare them via appearance of fragments of\u00a0 some of\u00a0 invented derivatives, Figures (6, 7):<\/p>\n\n\n\n
\"Figure<\/td>\nFigure <\/strong>6: Mass <\/strong>Spectrum of Invented Sulfazane -Trimethoprim <\/strong>{1}<\/strong><\/p>\n

Click here to View Figure<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"Figure<\/td>\nFigure 7<\/strong>: Mass <\/strong>Spectrum of Invented Sulfazane -Trimethoprim <\/strong>{2}<\/strong><\/p>\n

Click here to View Figure<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

All chemical with physical\u00a0 properties\u00a0 and information\u00a0 about\u00a0 TLC for\u00a0 invented derivatives in Table(1)<\/p>\n

Table 1: <\/strong>All\u00a0 chemical with physical\u00a0 properties\u00a0 and information\u00a0 of\u00a0 TLC\u00a0<\/strong><\/p>\n\n\n\n\n\n\n\n
Invented Derivatives<\/strong><\/td>\nProduct\u00a0 %<\/em><\/strong><\/td>\nColor<\/em><\/strong><\/td>\nM .P<\/em><\/strong><\/p>\n

(C \u00b0)<\/em><\/strong><\/td>\n

Rf<\/em><\/strong><\/td>\nSolvents (TLC)<\/em><\/strong><\/td>\n<\/tr>\n
Sulfazane-Trimethoprim {1}<\/strong><\/td>\n74<\/td>\nDeep Yellow<\/td>\n202<\/td>\n\u00a00.68<\/td>\nEthanol : Benzene<\/td>\n<\/tr>\n
Sulfazane-Trimethoprim {2} <\/strong><\/td>\n80<\/td>\nYellowish Orange<\/td>\n168<\/td>\n0.60<\/td>\nEthanol : Benzene<\/td>\n<\/tr>\n
Sulfazane-Trimethoprim {3}<\/strong><\/td>\n78<\/td>\nYellowish Orange<\/td>\n182<\/td>\n0.62<\/td>\nEthanol : Benzene<\/td>\n<\/tr>\n
Sulfazane-Trimethoprim {4}<\/strong><\/td>\n82<\/td>\n\u00a0\u00a0\u00a0\u00a0 Pale\u00a0 Orange<\/td>\n194<\/td>\n0.70<\/td>\nEthanol : Benzene<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Discussion<\/strong> Innovative Derivatives Test\u00a0 Against Breast Cancer<\/strong>Initialization of\u00a0 Cancer Cell Line<\/strong>(13)<\/sup><\/strong><\/p>\n

Line processing and implantation of breast cancer cells and\u00a0 live cell line were carried out at Biotechnology Center – the Nahrain (MCF-7 cell line) and (WRL cell line grew in\u00a0 95% of RPMI\u20131640) supplemented with (10% FBS), cell suspension and incubation(13, 53)<\/sup> at (37 \u00b0C) in incubator {(CO2<\/sub>) % 5}. The suspended cells were centrifuged at (250 g) for (10 minutes) and the supernatant was removed, the cells were re-suspended in a freezing medium, then placed at (-70 \u00b0C) in\u00a0 beaker for (1-3) days, the beaker was transferred from the standard freezer boxes to the liquid (N2<\/sub>) container.<\/p>\n

Processing\u00a0 Method<\/strong><\/p>\n

MTT was used to determine cell viability by chromatic examination(64-70)<\/sup> of two (MCF-7 and WRL cell lines):<\/p>\n

Cell suspension (100 \u00b5L) was added to the wells of a small flat plate bottom.<\/p>\n

The solution was prepared by dissolving the crystals of 5 mg MTT in 1 ml of PBS solution (phosphate buffer solution).<\/p>\n

The concentrations of each innovative derivative of the prepared derivatives were used in this research (500, 250, 125, 62.5 , 31.5 , 15.6 (\u00b5g\/ml of methanol, which were added to each well (three replicates per concentration).<\/p>\n

A 10 ml MTT solution was added to each well of a plate containing 96 wells and then incubated for 4 hours with a test sample at 37 \u00b0C (the solution became yellow).<\/p>\n

DMSO was added (200 \u00b5L (to each hole and stirred for 5 minutes (to become a purple DMSO solution).<\/p>\n

After the complete dissolution of the dye, the absorption of the colored solution from the living cells was read at (575 nm) using the ELISA reader.7-<\/strong> The mean absorption was calculated for each group of iterations and the validity ratio of the cells exposed to different treatments was obtained as follows(13)<\/sup>:<\/strong><\/p>\n

Cell Vitality% = [(Absorption from the treated sample \/Absorption from the untreated sample) X 100<\/strong><\/p>\n

Table <\/strong>2: Mean Percentage (%) for each cell line (<\/strong>Respond to Treatment<\/strong>)<\/strong> for\u00a0 Derivative{1}<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong>\u00a0<\/strong>Sulfazane- Trimethoprim{1}<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 IC50\u00a0 <\/sub><\/strong>\u00a0\u00a0(\u03bcg\/ml)<\/strong> \u00a0: ( 190. 1654 )<\/strong><\/td>\n<\/tr>\n
Mean Percentage\u00a0 (%)\u00a0 for each cell line (Respond to treatment )<\/strong><\/td>\n<\/tr>\n
Conc (\u03bcg\/ml)<\/strong><\/td>\nKilling and inhibition of Carcinoma Cells %<\/strong><\/td>\nToxic Effect\u00a0 on\u00a0 Normal Cell Line<\/strong><\/td>\n<\/tr>\n
\u00a0500<\/td>\n66 %<\/td>\n\u00a030 %<\/td>\n<\/tr>\n
\u00a0250<\/td>\n58 %<\/td>\n25 %<\/td>\n<\/tr>\n
125<\/td>\n50 %<\/td>\n25 %<\/td>\n<\/tr>\n
62.5<\/td>\n46%<\/td>\n20 %<\/td>\n<\/tr>\n
31.5<\/td>\n46 %<\/td>\n20 %<\/td>\n<\/tr>\n
15.6<\/td>\n44 %<\/td>\n20 %<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table <\/strong>3: Mean Percentage (%) for each cell line (<\/strong>Respond to Treatment<\/strong>)<\/strong> for\u00a0 Derivative{2}<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong>\u00a0<\/strong>Sulfazane- Trimethoprim{2}<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 IC50\u00a0 <\/sub><\/strong>\u00a0\u00a0(\u03bcg\/ml)<\/strong> \u00a0: (228. 1930)<\/strong><\/td>\n<\/tr>\n
Mean Percentage\u00a0 (%)\u00a0 for each cell line (Respond to treatment )<\/strong><\/td>\n<\/tr>\n
Conc (\u03bcg\/ml)<\/strong><\/td>\nKilling and inhibition of Carcinoma Cells %<\/strong><\/td>\nToxic Effect\u00a0 on\u00a0 Normal Cell Line<\/strong><\/td>\n<\/tr>\n
\u00a0500<\/strong><\/td>\n56 %<\/td>\n20 %<\/td>\n<\/tr>\n
\u00a0250<\/td>\n52 %<\/td>\n14 %<\/td>\n<\/tr>\n
125<\/td>\n46 %<\/td>\n14\u00a0 %<\/td>\n<\/tr>\n
62.5<\/td>\n40 %<\/td>\n14 %<\/td>\n<\/tr>\n
31.5<\/td>\n32 %<\/td>\n10 %<\/td>\n<\/tr>\n
15.6<\/td>\n30 %<\/td>\n10 %<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table <\/strong>4: Mean Percentage (%) for each cell line (<\/strong>Respond to Treatment<\/strong>)<\/strong> for\u00a0 Derivative{3}<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong>\u00a0<\/strong>Sulfazane- Trimethoprim{3}<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 IC50\u00a0 <\/sub><\/strong>\u00a0\u00a0(\u03bcg\/ml)<\/strong> \u00a0: (258. 5202 )<\/strong><\/td>\n<\/tr>\n
Mean Percentage\u00a0 (%)\u00a0 for each cell line (Respond to treatment )<\/strong><\/td>\n<\/tr>\n
Conc (\u03bcg\/ml)<\/strong><\/td>\nKilling and inhibition of Carcinoma Cells %<\/strong><\/td>\nToxic Effect\u00a0 on\u00a0 Normal Cell Line<\/strong><\/td>\n<\/tr>\n
\u00a0500<\/td>\n50 %<\/td>\n12 %<\/td>\n<\/tr>\n
\u00a0250<\/td>\n38 %<\/td>\n10 %<\/td>\n<\/tr>\n
125<\/td>\n36 %<\/td>\n10 %<\/td>\n<\/tr>\n
62.5<\/td>\n34 %<\/td>\n8 %<\/td>\n<\/tr>\n
31.5<\/td>\n30 %<\/td>\n8 %<\/td>\n<\/tr>\n
15.6<\/td>\n30 %<\/td>\n4 %<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table <\/strong>5: Mean Percentage (%) for each cell line (<\/strong>Respond to Treatment<\/strong>)<\/strong> for\u00a0 Derivative{4}<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong>\u00a0<\/strong>Sulfazane- Trimethoprim{4}<\/strong><\/td>\n\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 IC50\u00a0 <\/sub><\/strong>\u00a0\u00a0(\u03bcg\/ml)<\/strong> \u00a0: (210. 3871 )<\/strong><\/td>\n<\/tr>\n
Mean Percentage\u00a0 (%)\u00a0 for each cell line (Respond to treatment )<\/strong><\/td>\n<\/tr>\n
Conc (\u03bcg\/ml)<\/strong><\/td>\nKilling and inhibition of Carcinoma Cells %<\/strong><\/td>\nToxic Effect\u00a0 on\u00a0 Normal Cell Line<\/strong><\/td>\n<\/tr>\n
\u00a0<\/strong>500<\/td>\n\u00a060 %<\/td>\n22 %<\/td>\n<\/tr>\n
\u00a0250<\/td>\n\u00a050 %<\/td>\n18 %<\/td>\n<\/tr>\n
125<\/td>\n\u00a044 %<\/td>\n18 %<\/td>\n<\/tr>\n
62.5<\/td>\n\u00a040 %<\/td>\n16 %<\/td>\n<\/tr>\n
31.5<\/td>\n\u00a030 %<\/td>\n16 %<\/td>\n<\/tr>\n
15.6<\/td>\n\u00a030 %<\/td>\n16 %<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Conclusions<\/strong><\/p>\n

The results indicated\u00a0 to formation of these drug derivatives by appearance of new bands and disappearance of bands in starting compounds., besides to conclusions from our paper that gave good data for inhibition efficiency for these drug derivatives\u00a0 against cancer cells.\u00a0 Our\u00a0 results appeared\u00a0\u00a0 good\u00a0 inhibition for carcinoma\u00a0 cells line for all\u00a0 invented\u00a0 derivatives , and\u00a0 gave high\u00a0 response for\u00a0 derivatives {1\u00a0 and\u00a0 4} more\u00a0 than other\u00a0 invented\u00a0 derivatives ,(it was\u00a0 = 66 %\u00a0 response percentage\u00a0 of\u00a0 derivative {1} for\u00a0 inhibition and\u00a0 killing\u00a0 of cancer cells due\u00a0 to sulfazane(1, 2)<\/sup> group(-S-N=N- Drug ) that linked with\u00a0 drug which gave\u00a0 it\u00a0 more response\u00a0 against cancer cells also due to\u00a0 thiazole core\u00a0 in this derivative{1}.\u00a0<\/strong><\/p>\n

Acknowledgments <\/strong><\/p>\n

We would like to express our heartfelt thanks to \u00a0Biotechnology Center-the Nahrain for providing assistance\u00a0 samples of cells and\u00a0 bioinformatics analysis.<\/p>\n

Conflict of Interest<\/strong><\/p>\n

The authors declare that there is no conflict of interest.\u00a0 \u00a0<\/strong><\/p>\n

Funding Source<\/strong><\/p>\n

None<\/p>\n

References<\/strong><\/p>\n

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