A new chiral 2-(ethylthio)-thiazolone analogue shows strong antitumor activities by inducing cancer cell apoptosis and inhibiting angiogenesis.

Our initial study showed the potent cytotoxic effects of a series of new chiral 2-(ethylthio)-thiazolone analogues we synthesized. In the present study, we used computer prediction and found that nitro functionality and the modification of substituents R could further improve their activities in the presence of the nitro group. Compound 1s with nitro, naphthyl, ethyl groups, and a chiral center was predicted to be the most effective. We showed that compound 1s could inhibit the growth of five different cancer cell lines in a time-dependent and dose-dependent manner. 1s could induce Hela cell apoptosis by activating the mitochondria apoptotic pathway. In addition, 1s could inhibit the proliferation, migration, tuber formation, and adhesion of human umbilical vein endothelial cells, suggesting its antiangiogenesis effects. Furthermore, we confirmed the in-vivo antitumor effects of 1s on sarcoma S-180-bearing mice. Taken together, chiral 2-(ethylthio)-thiazolone analogue 1s is a promising compound for further anticancer drug development.