Regiospecific Synthesis of Thioether‐Linked 3‐Hydroxy Oxindoles From Spiroepoxy Oxindoles and Their Cytotoxicity Evaluation

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.