Design, synthesis and biological evaluation of novel diarylpyridine derivatives as tubulin polymerisation inhibitors.

ABSTRACT: A set of novel diarylpyridines as anti-tubulin agents were designed, synthesised using a rigid pyridine as a linker to fix the cis-orientation of ring-A and ring-B. All of the target compounds were evaluated for their in vitro antiproliferative activities. Among them, 10t showed remarkable antiproliferative activities against three cancer cell lines (HeLa, MCF-7 and SGC-7901) in sub-micromolar concentrations. Consistent with its potent antiproliferative activity, 10t also displayed potent anti-tubulin activity. Cellular mechanism investigation elucidated 10t disrupted the cellular microtubule structure, arrested cell cycle at G2/M phase and induces apoptosis. Molecular modelling studies showed that 10t could bind to the colchicine binding site on m

SUBMITTER: Yang S 

PROVIDER: S-EPMC9553186 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature