Novel Imidazopyridine-Oxadiazole Β-Tubulin Inhibitors Suppress Breast Cancer Migration and Induce Caspase-3 Apoptosis

Abstract

A series of novel imidazo[1,2-a]pyridine-oxadiazole (iMPZ1-15) hybrid compounds was designed as potential beta-tubulin polymerization inhibitors, inspired by the cis-conformation and biaryl scaffold of combretastatin A-4. The effects of iMPZ beta-tubulin inhibitors on proliferation in MDA-MB-231, SH-SY5Y, and DLD-1 cancer cells, as well as their influence on beta-tubulin inhibition, colonization, cell migration, cell cycle progression, and apoptosis in MDA-MB-231 cells, were investigated. iMPZ-8 identified as the most efficacious treatment candidate, with an IC50 value of 7.5 mu M in MDA MB-231 cells. iMPZ-8 had a comparable effectiveness to NOC, which served as a positive control for beta tubulin inhibition. IMPZ-8 reduced cellular migration and colonization. It also accumulated throughout the G2/M phase of the cell cycle, through the BAX-Caspase-3 intrinsic apoptotic signaling pathway.