Synthesis and biological activity of novel inhibitors of topoisomerase I: 2-Aryl-substituted 2-bis-1H-benzimidazoles

European Journal of Medicinal Chemistry
2011.0

Abstract

Inhibitors of topoisomerase I constitute a novel family of antitumor agents. The class of benzimidazole derivatives contains compounds possessing affinity to DNA. For example, fluorescent stains Hoechst 33342 and Hoechst 33258 interact with DNA as ligand and produce nonspecific inhibition of the catalytic activity of many enzymes involved in DNA synthesis, including DNA topoisomerase and DNA helicase. Several 2-aryl-5-substituted-2,5-bisbenzimidazole derivatives were synthesized and ability of these derivatives to induce DNA cleavage in the presence of topoisomerase I was evaluated in vitro. These analogs were also assayed for their cytotoxicity against U87, MCF7 and HeLa human tumor cells. All the four compounds showed a potent growth inhibitory effect on all the cell lines, with IC50 in the μM range.

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