Synthesis of imidazo[2,1-b][1,3,4]thiadiazole–chalcones as apoptosis inducing anticancer agents

Abstract

A series of new imidazo[2,1-b][1,3,4]thiadiazole–chalcones were synthesized by Claisen–Schmidt condensation and evaluated for their cytotoxic activity against various human cancer cell lines. These compounds showed moderate to appreciable antiproliferative activities. Interestingly, compounds like 11a and 11b exhibited significant cytotoxic activity with IC₅₀ values ranging from 0.65 to 2.25 μM in certain cancer cell lines. The structure–activity relationship (SAR) studies reveal that 3,4,5-trimethoxy group containing compounds showed superior cytotoxic activity against selected cancer cell lines compared to other chalcones. These compounds showed G₀/G₁ phase arrest, apart from activation of caspase-3 and 8 in DU-145 cells. The growth inhibitory effect of these compounds was associated with a decrease in cell cycle regulatory protein cyclin D1 and increase in cyclin dependent kinase inhibitors like Cip1/p21 and Kip1/p27.