Synthesis and antitumor activity of aza-brazilan derivatives containing imidazolium salt pharmacophores.

ABSTRACT: The synthesis of a series of novel aza-brazilan derivatives containing imidazolium salt pharmacophores is presented. The biological activity of such imidazolium salts was further evaluated in vitro against a panel of human tumor cell lines. The results suggest that the electron-withdrawing group on the aza-brazilan moiety, substituted 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methylbenzyl group were essential for modulating the cytotoxic activity. Compounds 55 and 39, bearing a 4-methylbenzyl substituent at position-3 of 5,6-dimethyl-benzimidazole, were found to be the most potent compounds with IC₅₀ values of 0.52-1.30 ?M and 0.56-1.51 ?M against four human tumor cell lines investigated. Particularly, compound 57 exhibited inhibitory activity against the MCF-7 cell line with an IC₅₀ value of 0.35 ?M and was 56-fold more sensitive than DDP. Moreover, compound 55 inhibited cell proliferation through inducing G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.

SUBMITTER: Huang M 

PROVIDER: S-EPMC6598646 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature