数量结构-活动关系
化学
计算化学
杂原子
密度泛函理论
分子描述符
轨道能级差
基准集
李宾斯基五定律
分配系数
试验装置
分子
数学
立体化学
有机化学
统计
生物化学
基因
生物信息学
戒指(化学)
作者
Samir Chtita,Mounir Ghamali,Abdellah Ousaa,Adnane Aouidate,Assia Belhassan,Abdelali Idrissi Taourati,Vijay H. Masand,Mohammed Bouachrine,Tahar Lakhlifi
出处
期刊:Heliyon
[Elsevier]
日期:2019-03-01
卷期号:5 (3): e01304-e01304
被引量:21
标识
DOI:10.1016/j.heliyon.2019.e01304
摘要
The quantitative structure-activity relationship (QSAR) of sixty 2-phenylimidazopyridines derivatives with anti-Human African Trypanosomiasis (anti-HAT) activity has been studied by using the density functional theory (DFT) and statistical methods. Becke's three-parameter hybrid method and the Lee-Yang-Parr B3LYP functional employing 6-31G(d) basis set are used to calculate quantum chemical descriptors using Gaussian 03W software, and the five Lipinski's parameters were calculated using ChemOffice software. In order to obtain robust and reliable QSAR model, the original dataset was randomly divided into training and prediction sets comprising 48 and 12 compounds, respectively. An optimal model for the training set with significant statistical quality was established. The same model was further applied to predict pEC50 values of the 12 compounds in the test set, further showing that this QSAR model has high predictive ability. It is very interesting to find that the anti-HAT of these compounds appear to be mainly governed by four factors, i.e., the number of H-bond donors, the lowest unoccupied molecular orbital energy, the molecular weight and the octanol/water partition coefficient. Here the possible action mechanism of these compounds was analysed and discussed, in particular, important structural requirements for great anti-HAT activity will be by increasing molecular size and substitute the 2-phenylimidazopyridines derivatives with polar, ionic, stronger accepting electron ability group and heteroatoms attached to one or more hydrogen atoms. Based on this proposed QSAR model, some new compounds with higher anti-HAT activities have been theoretically designed. Such results can offer useful theoretical references for future experimental works.
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