Volume 8 ; Issue 2 ; in Month : July-Dec (2025) Article No : 168
Priyadharshini R, Satish M, Neelambari S, et al.

Abstract

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 anti-alzheimer’s activity, they showed an IC50 value between 19 to 23μg/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.

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