Latest developments of spirooxindoles and their derivatives in medicinal chemistry

Spirooxindoles represent a pivotal class of heterocyclic compounds known for their diverse and potent biological activities. Naturally occurring spirooxindoles have been isolated from medicinal plants such as Flueggea virosa and Mitragyna speciosa, inspiring extensive research into their synthetic analogs. A variety of synthetic strategies, including multicomponent reactions, cycloaddition processes, and environmentally benign (green chemistry) approaches, have been developed to access structurally diverse spirooxindole derivatives. Recent investigations underscore their broad-spectrum bioactivity, including efficacy against drug-resistant bacterial and fungal pathogens, inhibition of the p53-MDM2 protein-protein interaction, and significant cytotoxicity against various human cancer cell lines. Advances in synthetic methodologies, notably microwave-assisted and catalyst-free protocols, have significantly improved the efficiency, selectivity, and sustainability of spirooxindole synthesis. This study summarizes recent developments in spirooxindole-containing compounds, both naturally isolated and synthetically prepared, reported in the last few years.