A facile green synthesis of 3,4-dihydropyrimidin-2(1H)-ones using cysteine as a bio-organic catalyst: Potent urease inhibitors, in vitro evaluation, kinetic mechanism, and molecular docking studies

The aim of the present research was to develop a one-pot, three-component method for the synthesis of some 3,4dihydro pyrimidine-2-(1H)-one (DHPM) derivatives using aldehydes, urea, and ethyl acetoacetate in the presence of cysteine as a green, bio-organic catalyst. This procedure has several key advantages, including a facile and convenient method, green and low-cost catalyst, high yield, short reaction time, and avoidance of the use of environmentally harmful solvents. It is important to note that the synthesized compounds (4a-j) were evaluated for in vitro urease inhibitory activity, and all were found to be more effective than the standard thiourea (IC50 = 4.745 & PLUSMN; 0.054 & mu;M), with urease inhibitory potentials between IC50 = 0.058 & PLUSMN; 0.006 & mu;M to 0.297 & PLUSMN; 0.066 & mu;M. Lineweaver-Burk plots were used to study the kinetics of the most potent compound (4e), and the results showed that the compound non-competitively inhibited urease by forming an enzyme-inhibitor complex. In addition, HT1080 human fibroblast cell lines were used to test the toxicity of the synthesized compounds on cell viability using the MTT assay method, and all compounds except 4g, 4i, and 4j exhibited no significant toxic effects on cells even at high concentrations. Moreover, molecular docking was used to determine the binding interactions between the molecules (ligands) and the active site of the urease enzyme, and the ligands indicated acceptable binding energy values.