Microwave-assisted synthesis of tubulin assembly inhibitors as anticancer agents by aryl ring reversal and conjunctive approach

Abstract

Microwave-assisted synthesis of new pyrrole and indole derivatives as tubulin assembly inhibitors was performed with remarkably improved yields and short reaction times. In designing the new inhibitors, aryl ring reversal and conjunctive approach notions were applied. (4-(4-Methoxyphenyl)-1-(pyridin-2-yl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone (4) inhibited [3H]colchicine binding by 78% and MCF-7 breast cancer cell growth with an IC50 of 9.6 nM. Compound 4 also inhibited the growth of HCT116, BX-PC3 and Jurkat cancer cells with IC50 values of 18, 17 and 41 nM, respectively, and altered the morphology of treated spheroids in both the BX-PC3 and HCT116 cell lines.