Green and One-Pot Synthesis of 4-(1H-Pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-diones and Assessment of Their Anticancer Activity

A series of 4-(1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine derivatives have been depicted by one-pot three component synthesis. The synthesis involved the reaction of 4-hydroxy-2H-chromen-2-one with 1H-pyrazole-5-carbaldehydes and urea/thiourea. The reaction was conducted in the presence of L-proline as a catalyst and ethanol as the solvent. This approach exhibits notable benefits like high yields, environmental compatibility, an easy procedure, short reaction periods, and mild reaction conditions. The synthesized compounds were examined for their cytotoxicity potential in HeLa and MCF-7 cells. Among all, 4-(1,4-dimethyl-1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione showed promising activity with IC₅₀ values 8.0 and 8.5 µM towards MCF-7 and HeLa cells, respectively. In addition, the docking studies revealed that 4-(1,4-dimethyl-1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione had a favorable binding energy of –9.4 kcal/mol in inhibiting the human Aldo-keto reductase 1C3.