2D QSAR, design, in-silico studies, synthesis, characterization and in-vitro evaluation of some novel 1,2,4 triazole as the effective anti-alzheimer’s agents inhibiting acetylcholinesterase enzyme

Background: Alzheimer's disease, characterized by cognitive decline, involves acetylcholinesterase (AChE) in acetylcholine degradation.Designing novel 1,2,4-triazole derivatives as AChE inhibitors may provide effective, safer treatments, overcoming limitations of existing therapies.Objective: The ligands are designed based on pharmacophoric features and docked against a specific target ACHE inhibitor.Performed 2D QSAR using QSARINs.The ligands are optimized based on drug likeness properties and toxicity profile.The optimized leads are synthesized, characterize and evaluate for Anti-alzheimer's activity against acetylcholinesterase enzyme.Methods: Docking and 2D QSAR experiments were used to generate a number of new 1,2,4 triazole derivatives, around 160 compounds were designed by using Chemsketch.Based on docking scores and QSAR studies, the best 5 compounds were synthesized using a variety of chemical processes.Spectroscopic methods were used to confirm the compounds' structures and also used to describe the compounds.The enzyme inhibition assay was used to assess their anti-alzheimer's activity against acetylcholinesterase enzyme.Results: When the synthesized compounds were tested for in-vitro antialzheimer's activity, they showed an IC50 value between 19 to 23g/ml, which was nearly as strong as the current standard medications (Rivastigmine).According to these results, PD35, PD65, and PD72 had the strongest inhibitory effects on acetylcholinesterase enzyme. Conclusion:The present study demonstrates the potential of 1,2,4 triazole derivatives as anti-alzheimer's agents against acetylcholinesterase enzyme.Further optimization and in-vivo evaluation are necessary to translate these findings into clinical applications.