L-proline.H2SO4 catalyzed synthesis of novel coumarin-based spiroindolino-3,4-dihydropyrimidin-2(1H)-ones: In-vitro cytotoxic assays and molecular docking study

Abstract

Abstract Development of environmentally benign catalyst system, especially those derived from readily available nature’s pool, in multicomponent synthesis consolidates multiple facets of green chemistry. Here, an L-proline derived green acid catalyst in the form of L-proline×H2SO4 was developed and employed for multicomponent synthesis of coumarin-based spiroindolino-3,4-dihydropyrimidin-2(1H)-ones from the reaction of 4-hydroxycoumarin, isatin and urea/thiourea. In this process, molecular building blocks having diverse biological activities such as antitumor, anti-inflammatory, and antitubercular activity were converged into a single molecular framework. Preliminary cytotoxicity studies showed that a couple of compounds (M5 and M6) have good cytotoxicity (40-50%) against in Dalton's Lymphoma (DL) cells, while demonstrating minimal cytotoxicity (10-12%) for normal non-cancerous cell line. Molecular docking simulations for the compounds M6 and M3, the compounds with heist and least cytotoxicity respectively, against Eg5 or Kinesin spindle protein (KSP) revealed the nature of interactions, estimated binding energy, and inhibition constants (Ki) of the compounds with KSP to corroborate with the experimental in-vitro cytotoxicity.