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.
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.
Hranjec
Marijana
M
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia.
Piantanida
Ivo
I
Kralj
Marijeta
M
Suman
Lidija
L
Pavelić
Kresimir
K
Karminski-Zamola
Grace
G
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000187:drug effects; D005449:Fluorenes / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects; D006801:Humans; D009691:Nucleic Acid Denaturation; D010777:Photochemistry; D012313:RNA / Q000737:chemistry* / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012313:RNA; D004247:DNA; D004264:DNA Topoisomerases, Type I