Cu(OTf)2 catalyzed three component strategy for the synthesis of thienopyridine containing spirooxindoles and their cytotoxic evaluation

Abstract

Synthesis of novel spirooxindoles via a three component reaction of thienopyridines, isatins and malononitriles under copper catalysis was accomplished. This one-pot, room temperature protocol allowed the synthesis of diversely substituted spirooxindoles in good to excellent yields. Cytotoxicity towards COLO320 cells revealed that compound 5v possessing a 2,6-difluorobenzyl group (IC₅₀ of 49.1 μM) was found to be highly potent among the screened compounds. In addition, molecular docking of compound 5v into caspase-3 receptors exhibited the largest binding energy (−10.5 kcal mol⁻¹) compared to other compounds. The formation of a DNA ladder for compound 5v also supports the experimental results.