Novel amidino-substituted thienyl- and furylvinylbenzimidazole: Derivatives and their photochemical conversion into corresponding diazacyclopenta[c]fluorenes. Synthesis, interactions with DNA and RNA, and antitumor evaluation. 4

摘要

Synthesis of novel nonfused amidino-substituted thienyl- and furyl vinylbenzimidazole: derivatives and their photochemical cyclization into corresponding diazacyclopenta[c]fluorenes is described. All studied compounds showed prominent growth inhibitor effect. The fused compounds showed stronger activity than nonfused ones, whereby imidazolyl-substituted compound 11 proved to be the most active one. Besides, it induced strong G2/M arrest of the cell cycle followed by drastic apoptosis, which is in accordance with the DNA intercalative binding mode determined by the spectroscopic studies. Nonfused derivatives induced strong S phase arrest of the cell cycle followed by apoptosis that together with DNA minor groove binding mode pointed to topoisomerase I inhibition. In addition, all nonfused compounds revealed pronounced selectivity toward tumor cells in comparison with nontumor cells. Oil the basis of the presented results, both nonfused and fused thiophene-containing, imidazolyl derivatives Should be considered as promising lead compounds for further investigation.