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, 1 H-, 13 C-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 ; IC 50 values 32.26 ± 0.12, 45.72 ± 0.11 µM, respectively), equine butyrylcholinesterase, BChE ( 9d , 9l , 9b , 10d , 10h ; IC 50 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 ; IC 50 values 7.27 ± 0.05, 7.35 ± 0.04, 8.79 ± 0.05 µM, respectively) and yeast α -glucosidase enzymes ( 9o , 10i ; IC 50 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.