a novel method for the synthesis of 1,2,4-triazole-derived heterocyclic compounds: enzyme inhibition and molecular docking studies

Two series of new n-aryl/aralkyl derivatives (9a–q) of 2-(4-ethyl-5-(thiophen-2-ylmethyl)-4h-1,2,4-triazol-3-ylthio)acetamide and n-aryl/aralkyl derivatives (10a–q) of 2-(4-phenyl-5-(thiophen-2-ylmethyl)-4h-1,2,4-triazol-3-ylthio)acetamide were synthesized. the methods included successive conversions of thiophen-2-acetic acid (a) into its respective ester, hydrazide and n-aryl/aralkyl 1,3,4-triazole. the target compounds (9a–q; 10a–q) were obtained by the reaction of n-aryl/aralkyl 1,3,4-triazole (5, 6) with various electrophiles, (8a–q), in n,n-dimethyl formamide (dmf) and sodium hydroxide at room temperature. the characterization of these compounds was done by ftir, 1h-, 13c-nmr, ei-ms and hr-ei-ms spectral data. all compounds were evaluated for their enzyme inhibitory potentials against electric eel acetylcholinesterase, ache (10f, 10d; ic50 values 32.26 ± 0.12, 45.72 ± 0.11 µm, respectively), equine butyrylcholinesterase, bche (9d, 9l, 9b, 10d, 10h; ic50 values 12.52 ± 0.19, 12.52 ± 0.19, 21.72 ± 0.18, 23.62 ± 0.22, 24.52 ± 0.21 µm, respectively), jack bean urease (10i, 10n, 9e; ic50 values 7.27 ± 0.05, 7.35 ± 0.04, 8.79 ± 0.05 µm, respectively) and yeast α-glucosidase enzymes (9o, 10i; ic50 values 62.94 ± 0.19, and 69.46 ± 0.15 µm, respectively). the molecular docking studies supported these findings. this study provides cheaper bioactive triazole amides as promising future lead molecules.