Identification of Novel Piperdinyl and Benzyl Piperdinyl Hydrazine Carbamide derivatives by Molecular Docking Studies as Potential antiamnesic agents against Acetyl cholinesterase Enzyme

Abstract

In this study, a series of novel Piperdinyl and Benzyl Piperdinyl Hydrazine Carbamide derivatives   were designed and evaluated for their binding affinity against Acetyl cholinesterase Enzyme using molecular docking studies to identify the potential lead compounds for Potential antiamnesic agents

The docking simulations were performed using AutoDock Vina against the diazepine binding site of the Acetyl cholinesterase Enzyme. several PBB derivatives demonstrated superior predicted binding affinity compared to E20. PBB-8 achieved the best docking score (−12.1 kcal/mol, IC₅₀ = 0.0013 µM, pIC₅₀ = 8.8747), indicating nearly 3.4-fold greater predicted potency than E20. Other strong performers included PBB-10 (−11.8 kcal/mol, IC₅₀ = 0.0022 µM, pIC₅₀ = 8.6547), PBB-3 (−11.4 kcal/mol, IC₅₀ = 0.0044 µM, pIC₅₀ = 8.3613), and PBB-5 (−11.4 kcal/mol, IC₅₀ = 0.0044 µM, pIC₅₀ = 8.3613), all comparable to or better than the reference ligand. Among the PAC derivatives, PAC-10 (−10.4 kcal/mol, IC₅₀ = 0.0236 µM, pIC₅₀ = 7.6279) emerged as the most potent binder, followed closely by PAC-8 (−10.2 kcal/mol, IC₅₀ = 0.0330 µM, pIC₅₀ = 7.4812) and PAC-5 (−10.0 kcal/mol, IC₅₀ = 0.0463 µM, pIC₅₀ = 7.3345). These compounds exhibited stronger predicted affinities compared to the rest of the series, likely due to enhanced hydrogen bonding and hydrophobic interactions at the active site.

The in silico ADMET profiling of the synthesized PBB and PAC derivatives reveals favourable drug-likeness and safety parameters, supporting their potential as antiamnesic agents, particularly targeting the Acetyl cholinesterase Enzyme.