Structural Variance of Doxorubicin and Anthracycline Analogues as Topoisomerase Alpha and Beta (Top2a and Top2b) Inhibitors. Potential Design of Analogue Candidates of Less Side Effects on Cardiomyocytes
Abdel-Nasser El-Shorbagi1,2*
, Sachin Chaudhary1, Hitesh Kumar3, Harish Chandra Verma4, Prabhash Nath Tripathi5, Aditi Giri5, Garima Agarwal5, Shweta Dumoga5 and Ramesh Kumar Gupta61Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
2Faculty of Pharmacy, University of Assiut, Assiut, Egypt.
3Department of Pharmaceutics, RV Institute of Pharmacy, Bijnor, Uttar Pradesh, India.
4Department of Pharmaceutical Chemistry, College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India.
5Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH-58, Baghpat Road Crossing, Bypass Road, Meerut, Uttar Pradesh, India.
6Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Lucknow, Uttar Pradesh, India.
Corresponding Author E-mail: aelshorbagi@sharjah.ac.ae
Abstract: Doxorubicin that is on WHO's list of essential medicines and other anthracycline analogues, in general, are natural metabolites isolated from Streptomycetaceae, or semi-synthetized derivatives stated as first-generation anticancer agents. The tetracyclic scaffold attached mostly to amino sugar is known to be effective against solid tumors compared to other anticancer agents. The mechanism had been stated as intercalating agent at the minor groove of DNA strands during the step of releasing supercoiled DNA. Along with their anticancer activity, anthracyclines possess antimicrobial effects of notable MIC values. Cardiotoxicity represents the main challenge for both of medical care for treatment of cancers and drug discoverers. This exertion deals with careful structural investigation of the three-dimensional, fully optimized drugs in use. Drug-candidates in clinical studies, and leads failed in last developments. The aim is to find a structural gate to guard against or reduce the cardiac side effects. It deals also, with the topological features differentiating between antibacterial and anticancer agents bearing the tetracyclic scaffold features as well as between the topoisomerases as target molecules.
Keywords: Anticancer Activity; Anthracycline; Cardiac Toxicity; Doxorubicin; Fully Optimized 3D Structure; Gene; Topoisomerase Top2A; Topoisomerase Top2B Back to TOC