Deoxyribonucleic Acid Topoisomerase Inhibitors

摘要: Drugs that inhibit the action of topoisomerase enzymes (regulatory catalyze breakage and religation DNA) are an important class anticancer drugs. The drugs bind reversibly to form ternary drug–DNA–enzyme complexes result in cytotoxic DNA breaks, primarily by preventing relegation step. usually classified their spectrum inhibition, as inhibitors topo I, II, or both (dual I/II inhibitors). majority II dual intercalators, where a flat polyaromatic drug chromophore intercalates between base pairs, driven stacking electrostatic interactions. There is also substantial diverse with little direct affinity but which nevertheless complexes. Inhibitors I latter type, most being analogs natural product camptothecin. major deficiencies this instability essential E ring lactone susceptibility cell efflux mechanisms, new attempt improve these. mostly cardiotoxicity and, again, pumps. While issue has been quite well addressed, many still susceptible transport-mediated resistance. evidence some newer may act additional mechanisms. Finally, represent newest topoisomerase-active it not clear whether such inhibition advantage, considerable structural diversity, members inhibiting novel manner, others suspected working nontopoisomerase