Trimethoxyphenyl-1,2,4 Synthesis, Characterization, DFT, Antimicrobial and Acetylcholinesterase Inhibitory Activities with Molecular Docking and Dynamics Studies

Abstract

5-alkyl/aryl-4-(3,4,5-trimethoxyphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (2a-2f) were synthesized and confirmed by FTIR, 1H- and 13C-NMR spectroscopic methods. The details of molecular structure the compounds were investigated by DFT calculations. All the theoretical study was carried out at DFT/B3LYP/6-311 + + G(d,p) level. The optimized geometries, IR and NMR specral data, MEP maps of compounds 2a-2f were obtained theoretically. The spectral data were compared with the experimental ones and the molecular structures of compounds were investigated in detailed. The results indicate the presence of strong intermolecular hydrogen bonds of N-H & sdot;& sdot;O type in the molecular structure of compounds 2a-2f. The biological evaluation demonstrated that all compounds exhibited antimicrobial activity with MIC values ranging from 156 to 1250 mu g/mL. In particular, compounds 2c, 2d, and 2f showed the strongest antifungal effects against Candida albicans (MIC = 156 mu g/mL), while compounds 2a, 2b, and 2e also showed moderate antifungal activity (MIC = 312 mu g/mL). Compound 2b further exhibited the most potent acetylcholinesterase (AChE) inhibitory activity (IC50 = 13 mu M) among the series. These findings identify compound 2b as a promising dual-activity molecule with both AChE inhibitory and antimicrobial properties. Compounds were also tested for their biological activities, the antimicrobial screening indicated that compounds 2c, 2d, and 2f exhibited moderate inhibitory activity, particularly against Candida albicans. Compound 2b showed the highest acetylcholinesterase (AChE) inhibitory activity among the series, with an IC50 value of 13 mu M. Moreover, molecular docking and molecular dynamics simulations were performed to investigate the binding interactions between the newly synthesized compound 2b and human acetylcholinesterase (hAChE).