engleski

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. Part 4

Synthesis of novel non-fused amidino-substituted thienyl- and furyl-vinyl-benzimidazole derivatives and their photochemical cyclization into corresponding diaza-cyclopenta[c]fluorenes is described. All studied compounds showed prominent growth inhibitory effect. The fused compounds showed stronger activity than non-fused 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. Non-fused 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 non-fused compounds revealed pronounced selectivity toward tumor cells in comparison with non-tumor cells. Based on the presented results, both non-fused and fused tiophene-containing imidazolyl-derivatives should be considered as promising lead compounds for further investigation.

benzimidazoles ; amidines ; cyclopenta[c]fluorenes ; interaction with DNA and RNA ; antitumor evaluation

nije evidentirano