Synthesis, in silico and in vitro studies of hydrazide‐hydrazone imine derivatives as potential cholinesterase inhibitors

A series of hydrazide-hydrazone imine derivative compounds (3a-k) were synthesized and their structures characterized using FTIR, 1 H, and 13 C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X-ray diffraction technique. In vitro inhibition activities of hydrazide-hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC50 = 2.01 μM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC50 = 2.60 μM). Against BChE, compound 3h (IC50 = 2.83 μM) showed the best inhibitory property which is higher control Galantamine (IC50 = 3.70 μM). The Ki values of compound 3i (Ki = 0.63 μM) and compound 3h (Ki = 0.94 μM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of -10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is -8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties.