Synthesis, in-vitro inhibition of cholinesterase and in silico studies of new hydrazide-hydrazones derived from Clopidogrel

Due to the lack of an effective treatment for Alzheimer's disease, there is a need for the development of new and effective compounds. The synthesis of some new hydrazone derivatives (TA1-TA14) based on Clopidogrel bisulfate has been carried out. IR, 1H-NMR, 13C-NMR, 2D-NMR (HSQC) and MS spectroscopic techniques were used to elucidate the chemical structures of the compounds. Antioxidant and cholinesterase activities of the compounds were evaluated. Compound TA2 bearing bromo substituent has the highest antioxidant activity in the series. Compound TA11 bearing methoxy substituent exhibited the highest inhibitory activity in the series with IC50 values of 8.540±0.015 µM and 7.980±0.026 μM against AChE and BChE, respectively. Kinetic studies (Lineweaver-Burk plots) revealed that TA11 was a competitive inhibitor. In addition, molecular docking studies aimed to elucidate the interactions between these designed compounds and key enzymes, including AChE and BChE. TA11 has been evaluated as a promising candidate for further studies to develop new agents in the fight against Alzheimer's disease.