Topoisomerase I and II inhibitors: chemical structure, mechanisms of action and role in cancer chemotherapy

Stereoselective synthesis of 11-phenylundeca-5Z,9Z-dienoic acid and investigation of its human topoisomerase I and IIα inhibitory activity

“…[1][2][3][4][5][6] The literature describes quite a few low-molecular-weight chemical compounds 7-15 that are able, owing to their lipophilic nature, to penetrate into the cell nuclei, interact with DNA or block DNA-dependent enzymes and, hence, change indirectly the local conformation of the DNA molecules, thus inducing strand cleavage or disturbing the matrix synthesis. The DNA damage results in violation of the cell cycle and cell viability, and, hence, the therapeutic effect is achieved: retardation of proliferation and tumor destruction.…”

Catalytic cyclometallation in steroid chemistry III1Steroids 78 (12–13) (2013) 1298–1303 (http://dx.doi.org/10.1016/j.steroids.2013.09.007).1: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity

“…An important enzyme in this series is DNAdependent topoisomerase I, which catalyzes the topological rearrangements of DNA and plays key role in all aspects of genome functioning [1][2][3]. The topoisomerase-induced breaks in one (topoisomerase I) or two (topoisomerase II) DNA strands followed by repair and restoration of integrity of the DNA molecule provides the mobility needed for conformational changes of DNA in the template-directed synthesis and chromosome mobility during mitosis.…”

“…The topoisomerase-induced breaks in one (topoisomerase I) or two (topoisomerase II) DNA strands followed by repair and restoration of integrity of the DNA molecule provides the mobility needed for conformational changes of DNA in the template-directed synthesis and chromosome mobility during mitosis. Topoisomerases are considered as intracellular targets for chemotherapeutic agents, as by preventing the break repairs, these substances can induce accumulation of damaged DNA molecules, thus promoting the cell death [1][2][3].…”

“…They were found among compounds of various classes, which can be used to elucidate the structure-property relationships in order to optimize the known pharmaceutical drugs and synthesize new ones [2,3].…”

Diazapyrenes: interaction with nucleic acids and biological activity

“…Since replication processes are ongoing in tumor tissues, these cells are the most vulnerable to the action of topoisomerase inhibitors. 27 Attention to azapyrenes is associated both with theoretical aspects and with the results of practical application. Polyazapyrenes are actively used to create molecular devices, 28 redox sensors, 29 compounds with a topological bond, 30 host-guest molecules, 31 and macrocomplexes with transition metal cations.…”