Bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment exerting potent antiproliferative activity through microtubule destabilization.

Abstract Novel bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment as antiproliferative agents by targeting tubulin were synthesized and their preliminary structure activity relationships (SARs) were explored. Among all these chemical agents, 2-(Benzo[d]oxazol-2-ylthio)- N -(4-methoxybenzyl)- N -(3,4,5-trimethoxyphenyl)acetamide (4d) exhibited the potent antiproliferative activity against MGC-803 cells with an IC 50 value of 0.45 μM by induction of G2/M pahse arrest and cell apoptosis. In addition, 4d could change the membrane potential (ΔΨ) of the mitochondria against MGC-803 cells. Importantly, 4d acted as a novel tubulin polymerization inhibitor binding to colchicine site with an IC 50 value of 3.35 μM. Graphical abstract Image 1 Highlights • 4d exhibited the potent antiproliferative activity against MGC-803 cells. • 4d induced cell cycle G2/M phase arrest and apoptosis. • 4d changed the mitochondrial membrane potential against MGC-803 cells. • 4d acted as a novel colchicine site tubulin polymerization inhibitor. [ABSTRACT FROM AUTHOR]