Farzaneh MohamadpourHesam KamyabShreeshivadasan ChelliapanAli Mohammad Amani2025-03-282025-03-282024-11-08https://doi.org/10.1002/slct.202502085The current work provides a novel green method for creating dihydropyrimidinone (DHPM) scaffolds utilizing copper-doped carbon quantum dots (Cu-CQDs) as an environment-friendly and effective heterogeneous catalyst in the search for a green and sustainable catalytic approach. In accordance with green chemistry principles, Cu-CQDs catalytic effectiveness was proven in the Biginelli reaction, producing DHPM derivatives in mild, solvent-free conditions. Additionally, using in silico DFT and molecular docking studies, the produced DHPM compounds were assessed first time for their ability to block the pepsin enzyme, demonstrating robust binding interactions inside the active site of the enzyme. Based on the promising docking results, all the DHPM derivatives were subjected to in vitro enzymatic assay, confirming their potential as effective pepsin inhibitors with inhibition ranging from 1.99 ± 0.9 M to 8.98 ± 1.9 M at a concentration of 10−6 M. The obtained IC50 value of 1.99 ± 0.9 × 10−6 M indicated that the compound RJ10 was the best inhibitor. Cu-CQDs catalyzed DHPMs emerged as a novel class of pepsin inhibitors with potential applications in medicinal chemistry is highlighted by the combined computational and experimental insights. This study provides the pathway for further developments of DHPM derivatives as digestive enzyme inhibitors.journal-article