Chemoinformatics Study of Benzodiazepine-1, 2, 3-triazole Derivatives Targeting Butyrylcholinesterase

This study aims to assess the potential bioactivity of newly designed benzodiazepine-1,2,3-triazole derivatives using in-silico methodologies, with a primary focus on elucidating their inhibitory interactions with the butyrylcholinesterase (BuChE) enzyme, which is implicated in Alzheimer’s disease. We employed multiple linear regression (MLR) methods to conduct a quantitative structure-activity relationship (QSAR) analysis on a collection of 31 benzodiazepine-1,2,3-triazole derivatives, with the goal of investigating, assessing, and predicting their activities, as well as designing novel compounds. This approach yielded highly accurate results, with coefficients of determination (R²) of 0.77 and 0.81 for the training and test datasets, respectively. Additionally, the optimized compounds were subjected to an Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, demonstrating their potential as non-hepatotoxic agents with enhanced absorption and blood-brain barrier permeability. To further validate these findings, the most favorable docking conformations were analyzed using molecular dynamics (MD) simulations with GROMACS software, predicting the stability of the formed complexes. These simulations underscored the critical role of hydrogen bonds in stabilizing the compounds at the BuChE receptor binding site. The results hold great promise for the development of innovative benzodiazepine-1,2,3-triazole derivatives as effective BuChE inhibitors, potentially leading to therapeutic interventions for Alzheimer’s disease.