Design, synthesis and anticancer mechanistic studies of linked azoles

Abstract

Herein we report the synthesis and biological activity evaluation of 2,4 linked azole-containing molecules. A total of 13 linked thiazole- and oxazole-containing compounds were synthesized in good yields. Cytotoxicity evaluation of those compounds showed that they have low-micromolar anticancer potency against HCT116 colon cancer cells. Mechanism of action investigation studies indicated that linked thiazoles were significantly more biologically active than the corresponding oxazole-containing molecules in inducing apoptotic cancer cell death. Incorporation of a stereocenter at an azole end and an amide cap at the other end provided a compound that induces DNA damage and leads to G2/M cell cycle arrest and activation of the G2/M DNA damage checkpoint.