New spirooxindole pyrrolidine/pyrrolizidine analogs: design, synthesis, and evaluation as an anticancer agent

Abstract

A novel series of mesitylene-based spirooxindoles were synthesized via the multicomponent [3 + 2] cycloaddition reaction in a greener medium. Spectroscopic techniques such as ¹H and ¹³C NMR and HRMS analysis were carried out for the structural elucidation of all the spirooxindole derivatives. The in vitro cytotoxicity properties of spirooxindole analogs 4/5(a–g) against the human lung (A549) cancer cell line exhibited encouraging outcomes. Of the fourteen synthesized spirooxindole analogs, seven compounds (4a, 4b, 4e, 4g, 5c, 5e, and 5f) showed greater potency towards the A549 lung cancer cell line. The cytotoxicity of the spirooxindole analogs was also investigated against a non-cancerous mouse embryonic fibroblast NIH-3T3 cell line. Compounds 5e and 5f, which exhibited better cytotoxic effect against the cancerous A549 cells (3.48 and 1.2 μM), appeared to be non-cytotoxic against the non-cancerous mouse embryonic fibroblast. Studies using Hoechst and acridine orange/ethidium bromide staining also demonstrated the apoptotic effect of the potent compounds, which decreased cell proliferation.