2-Anilinonicotinyl linked 1,3,4-oxadiazole derivatives: Synthesis, antitumour activity and inhibition of tubulin polymerization

Abstract

A series of 2-anilinonicotinyl linked 1,3,4-oxadiazoles was synthesized and evaluated for their antitumour activity against various cancer cell lines, inhibition of tubulin polymerization and cell cycle effects. Some of these compounds showed good antiproliferative activity with GI₅₀ values ranging from 4.57 to 97.09 μM in the human cancer cell lines and one of the compounds 5m showed potent antitumour efficacy in all the cell lines tested. This compound also inhibited tubulin polymerization under both in vitro and in vivo conditions. Analysis of tubulin by Western blot experiments demonstrated that 5m depolymerizes microtubules by causing disturbances in the ratio of soluble versus polymerized tubulin in cells, leading to the cell cycle arrest at G2/M phase of the cell cycle followed by activation of caspase-3 activity and apoptotic cell death.