Synthesis and acetylcholinesterase enzyme inhibitory effects of some novel 4,5-Dihydro-1H-1,2,4-triazol-5-one derivatives; an in vitro and in silico study

In this study, a series of novel Schiff bases (4a-4h) containing 1,2,4-triazole structure were synthesized through a condensation reaction of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones with 3-(4-methylbenzenesulfonyloxy)-benzaldehyde. The structures of 3-alkyl(aryl)-4-[3-(4-methylsulfonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a-h) were determined through a range of spectroscopic techniques (FT-IR, H-1 NMR, C-13 NMR, and elemental analysis). In addition, enzyme inhibitory properties of the newly synthesized Schiff bases were determined against acetylcholinesterase (AChE). Their K-i values were calculated in the range of 0.70 +/- 0.07-8.65 +/- 5.6 mu M. Besides, their IC50 values were calculated in the range of 0.43-3.87 mu M. Finally, in silico molecular docking interactions of the compounds with AChE target enzyme (PDB ID:4EY7) were evaluated using Chimera and AutoDock Vina softwares. The lowest binding energy levels (-12.0 kcal/mol) of the compounds 4e and 4g with AChE target enzyme were verified the best binding affinities and molecular interactions. Communicated by Ramaswamy H. Sarma