塔克林
数量结构-活动关系
化学
试验装置
分子描述符
拓扑(电路)
胆碱酯酶
极表面积
力矩(物理)
生物信息学
立体化学
分子模型
计算化学
分子
乙酰胆碱酯酶
数学
药理学
机器学习
有机化学
计算机科学
酶
生物化学
组合数学
医学
物理
经典力学
基因
作者
Imad Hammoudan,Samir Chtita,Ossama Daoui,Souad Elkhattabi,Mohamed Bakhouch,Mohamed El Yazidi,Farhan Siddique,Driss Riffi-Temsamani
出处
期刊:Letters in Drug Design & Discovery
[Bentham Science]
日期:2023-06-01
卷期号:20 (6): 699-712
被引量:3
标识
DOI:10.2174/1570180819666220512174409
摘要
Introduction: This work was devoted to an in silico investigation conducted on twenty-eight Tacrine-hydroxamate derivatives as a potential treatment for Alzheimer’s disease using DFT and QSAR modeling techniques. Methods: The data set was randomly partitioned into a training set (22 compounds) and a test set (6 compounds). Then, fourteen models were built and were used to compute the predicted pIC50 of compounds belonging to the test set. Results: All built models were individually validated using both internal and external validation methods, including the Y-Randomization test and Golbraikh and Tropsha's model acceptance criteria. Then, one model was selected for its higher R², R²test, and Q²cv values (R² = 0.768, R²adj = 0.713, MSE = 0.304, R²test=0.973, Q²cv = 0.615). From these outcomes, the activity of the studied compounds toward the main protease of Cholinesterase (AChEs) seems to be influenced by 4 descriptors, i.e., the total dipole moment of the molecule (μ), number of rotatable bonds (RB), molecular topology radius (MTR) and molecular topology polar surface area (MTPSA). The effect of these descriptors on the activity was studied, in particular, the increase in the total dipole moment and the topological radius of the molecule and the reduction of the rotatable bond and topology polar surface area increase the activity. Conclusion: Some newly designed compounds with higher AChEs inhibitory activity have been designed based on the best-proposed QSAR model. In addition, ADMET pharmacokinetic properties were carried out for the proposed compounds, the toxicity results indicate that 7 molecules are nontoxic.
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