Synthesis and antiproliferative activity in vitro of new 2-aminobenzimidazole derivatives. Reaction of 2-arylideneaminobenzimidazole with selected nitriles containing active methylene group

Abstract

A series of pyrimido[1,2-a]benzimidazole and α-cyanocinnamic acid derivatives have been synthesized in the reactions of Schiff bases 2–7 with selected nitriles containing an active methylene group: malononitrile 8–12, cyanoacetamide 13–16, benzyl cyanide 17–21, benzoylacetonitrile 22–24, cyanoacetate methyl ester 25–28 and benzylacetamide 29. The structures 8–29 were confirmed by the results of elementary analysis and their IR, 1H-, 13C-NMR and MS spectra. The products 8–29 of various chemical structure pyrimido[1,2-a] benzimidazole 8–12, 14–16, 17–21, 23–24, 26 and α-cyanocinnamic acid derivatives 13, 22, 25, 27, 28 were obtained, which are of interest for biological studies or which can be substrates for further synthesis. The selected compounds 10, 13, 14, 17, 19, 21, 23–25 and 28 were screened for their antiproliferative activity in vitro against neoplastic and normal cell lines. The most active two compounds were: 2-(o-bromophenylene)-3-cyano-4-phenyl-1,2-dihydropyrimido[1,2-a]benzimidazole (24) and 3-cyano-4-phenyl-2-(2,4-dimethoxyphenyl)-1,2-dihydropyrimido[1,2-a]benzimidazole (23). However, similarly like cisplatin used as the control, they showed no selectivity towards cancer cells, by inhibiting proliferation of normal mouse fibroblasts in similar manner.