H 2 O‐Mediated Epoxide Ring‐Opening with Concomitant C–S Bond Formation: A One‐Pot Method to 3‐Hydroxy‐oxindolino‐dithiocarbamates as Cytotoxic Agents

A simple and efficient one‐pot protocol for the synthesis of a library of 3‐hydroxy‐oxindolino‐dithiocarbamate hybrids has been developed and evaluated for their in vitro cytotoxicity potential against selected human cancer cell lines. This one‐pot reaction takes place via regiospecific spiro‐epoxide ring‐opening with concomitant C–S bond formation by an in situ generation of dithiocarbamate intermediate. Gratifyingly, the reaction has been accelerated efficiently in water medium without using any catalyst or base and enable higher yields, atom‐economy, greener synthesis and offers diverse substrate scope. Among the tested compounds, one of the representative compounds 4 p with a chloro substitution and N‐ p ‐CN‐benzyl on oxindole nucleus displayed potent in vitro cytotoxicity against MCF‐7 (breast cancer cells) with an IC 50 value of 2.1 ± 0.4 μM. Moreover, the promising candidate 4 p induce G2/M phase cell cycle arrest and apoptosis on MCF‐7 cells, as determined by AO‐EB and DAPI staining as well as annexin binding studies