Abstract

A facile synthesis of thioether-linked 3-hydroxy oxindoles was achieved through regiospecific ring-opening of spiroepoxy oxindoles with oxadiazole-2-thiols and benzimidazole-2-thiols as nucleophiles. The thiol heteronucleophile attacks from the less hindered position of spiroepoxides, yielding 3-substituted-3-hydroxy oxindoles in high yields (up to 86%). The synthetic procedure offers an attractive route for diversely substituted 3-hydroxy oxindoles that are prominent frameworks in many natural products. Further, the in vitro cytotoxicity evaluation shows that most of these molecules possessed considerable cytotoxic activity against a panel of human cancer cell lines by comparing 5-fluorouracil (5-FU) as control. The morphological studies like phase contrast, AO/EB, and DAPI of the most potent compound 5e highlight apoptotic features on skin melanoma cell lines (SKMEL-29). Additionally, compound 5e was also studied for inhibition of tubulin polymerization, and the result was correlated with molecular docking studies.