Clay catalyzed dihydropyrimidinone synthesis: α-glucosidase inhibition and chemoinformatics

Abstract

This research focuses on the synthesis of 1,2,3,4-tetrahydropyrimidine-5-carboxamide derivatives via the Biginelli reaction, a renowned one-pot MCR that employs three key reactants a β-keto ester, an aryl aldehyde and urea. In the current study, employing Montmorillonite K-10, a heterogeneous green clay catalyst led to a faster reaction and a yield of 85–93 %. This catalyst offers a large surface area, enhancing reactants efficiency and accelerating the reaction rate. Molecular structures of the target compounds were elucidated using FT-IR, ¹H NMR, ¹³C NMR and Mass spectrometry. The HOMO-LUMO energy gap, MEP values and vibrational frequencies were investigated through DFT studies to evaluate reactivity and for theoretical-experimental correlations. Using ADMETlab 2.0, ADMET properties were examined to determine the drug-likeness of the targets. In-silico docking simulations were performed to analyze ligand-enzyme interactions and assess the binding affinity of target compounds toward the α-Glucosidase receptor. Synthesized compounds were screened for anti-diabetic activity using in-vitro α-Glucosidase Inhibition Assay.