title: SYNTHESIS AND IN VITRO ANTIPROLIFERATIVE ACTIVITY OF NOVEL 2-ARYLIDENEAMINOBENZIMIDAZOLE DERIVATIVES.
abstract: A new class of Mannich bases 9-26, derivatives of 2-amino-1H-benzimidazole, were obtained in the condensation of Schiff bases 1-4 or 2-benzylaminobenzimidazoles 5-8 with selected secondary amines: morpholine, piperidine, N-methylpiperazine, N-phenylpiperazine, 1-(2-pyridyl)piperazine, 1(2-methoxyphenyl)piperazine, 1-(2-pyrimidinyl)piperazine and formaldehyde in ethanol. The pyrimido[1,2-albenzimidazole derivatives 27-29 have been synthesized in the reactions of Schiff base 2 with selected compounds containing active methylene group: acetylacetone, benzoylacetone and malononitrile. The structures 1-29 were confirmed by the results of elementary analysis and their IR, 1H- and 13C-NMR spectra. The products 1-29 are of interest for biological studies and can be substrates for further synthesis. All compounds were screened against the cells of MV4-11 human leukemia and then the most active of them 5, 7, 9-16, 24-26, 28, 29 were tested towards human T47D breast and A549 lung cancer cells as well as normal mouse fibroblasts (BALB/3T3). The most active compound against the cancer cell lines was 4-amino-3-cyano-2-(4-hydroxyphenylene)-1,2-dihydropyrimi-do[1,2-a]benzimidazole (29) (IC50 0.23 ± 0.05 µg/mL against MV4-11 cells) showing in parallel very low cytotoxicity towards mouse fibroblasts. Cisplatin was the control drug.
authors.forename: Anna
authors.initials: A
authors.lastname: Nowicka
authors.forename: Hanna
authors.initials: H
authors.lastname: Liszkiewicz
authors.forename: Wanda P
authors.initials: WP
authors.lastname: Nawrocka
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Sadowska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D041702:BALB 3T3 Cells; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles