Synthesis and acetylcholinesterase enzyme inhibitory effects of some novel 4,5-Dihydro-1 H -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-1 H -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-1 H -1,2,4-triazol-5-ones (4a-h) were determined through a range of spectroscopic techniques (FT-IR, 1 H NMR, 13 C 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 µM. Besides, their IC 50 values were calculated in the range of 0.43-3.87 µM. 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.