Journal of medicinal and pharmaceutical chemistry 2008-08-28

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.

Marijana Hranjec, Ivo Piantanida, Marijeta Kralj, Lidija Suman, Kresimir Pavelić, Grace Karminski-Zamola

Index: J. Med. Chem. 51 , 4899-910, (2008)

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Abstract

Synthesis of novel nonfused amidino-substituted thienyl- and furylvinylbenzimidazole: derivatives and their photochemical cyclization into corresponding diazacyclopenta[ c]fluorenes is described. All studied compounds showed prominent growth inhibitory 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. On the basis of the presented results, both nonfused and fused thiophene-containing imidazolyl derivatives should be considered as promising lead compounds for further investigation.