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

Development of environmentally benign catalyst systems, 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. 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 lines. Molecular docking simulations for the least and most cytotoxic compounds, M3 and M6 respectively, against nineteen tumor target proteins were carried out, and seven of them were identified to test against all the sixteen compounds. Based on the estimated docking score and inhibition constants (K_i), the interaction of the compounds with the tumor target protein, beta-hexosaminidase B (PDB ID: 1NOW) matched closely with in vitro cytotoxicity data.