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.

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.