Design, stereoselective synthesis and anticancer efficacy of a new class of functionalized pyrrolizidine heterocyclic hybrids

Abstract

Eight new functionalized spirooxindole-pyrrolizidine heterocyclic hybrids has been obtained from N-pyridinylmethyl-bisarylmethylidene-pyridinones, Isatin and L-Proline by a multi-component cycloaddition reaction. Such synthesized derivatives are being characterized systematically with the aid of instrumental facilities like FT-IR, NMR spectroscopy, and Mass spectrometry. Following this, all the compounds are tested for the anticancer potentials in vitro using HepG2 cells (cancer cells). The compound with no substitution on the aryl rings (phenyl rings), displayed the highest activity among the spirooxindole-pyrrolizidines. Further the most active heterocyclic hybrids are verified for toxicity effects against L929 cells (non-cancer cells; at 200 µg/mL for 24 h). Finally, the cell viability losses for these most active compounds (at its IC50 value) are addressed by assaying the activity of free radicals, apoptosis, and caspases.

Keywords

• Cycloaddition reaction
• Spirooxindole-pyrrolizidines
• Anticancer activity
• ROS generation
• Caspase-3 activity
• Apoptosis