Abstract：
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.
摘要：
本研究旨在评估新设计的苯并二氮杂-1,2,3-三唑衍生物的潜在生物活性，主要集中在阐明它们与丁酰胆碱酯酶（BuChE）酶的抑制性相互作用，这与阿尔茨海默病有关。我们采用多元线性回归（MLR）方法对31种苯二氮卓-1,2,3-三唑衍生物进行定量构效关系（QSAR）分析，为了调查，评估,预测他们的活动，以及设计新型化合物。这种方法产生了非常准确的结果，训练和测试数据集的确定系数(R²)为0.77和0.81，分别。此外,对优化的化合物进行吸收，Distribution,代谢，排泄,和毒性(ADMET)分析，证明了它们作为非肝毒性药物的潜力，具有增强的吸收和血脑屏障通透性。为了进一步验证这些发现，用GROMACS软件使用分子动力学(MD)模拟分析了最有利的对接构象，预测形成的配合物的稳定性。这些模拟强调了氢键在稳定BuChE受体结合位点的化合物中的关键作用。结果为开发创新的苯二氮卓-1,2,3-三唑衍生物作为有效的BuChE抑制剂提供了巨大的希望，可能导致阿尔茨海默病的治疗干预。
