数量结构-活动关系
奥西多尔
对接(动物)
偏最小二乘回归
生物信息学
化学
计算生物学
李宾斯基五定律
酪氨酸激酶
立体化学
生物化学
药理学
生物
信号转导
计算机科学
机器学习
医学
护理部
催化作用
基因
作者
Jalalaldin Zangeneh,Pouria Shirvani,Mahmoud Etebari,Lotfollah Saghaie
出处
期刊:Journal of computational biophysics and chemistry
[World Scientific]
日期:2022-04-21
卷期号:21 (05): 583-598
被引量:2
标识
DOI:10.1142/s2737416522500223
摘要
Recently, anti-cancer targeting drugs are directed against specific molecules and signaling pathways. These targeting agents have reasonable specificity, efficacy and less side effects. Tyrosine kinases, which play an essential role in growth factor signaling regulation, are significant targets in this type of therapy. Synthesized numerous tyrosine-kinase inhibitors (TKIs), such as substituted indolin-2-ones, are effective as anti-tumor and anti-leukemia agents. In this study, a series of novel substituted indolin-2-ones were studied as kinase inhibitor analogs through quantitative structure–activity relationship (QSAR) analysis. Two chemometrics methods, such as multiple linear regression (MLR) and partial least squares combined with genetic algorithm for variable selection (GA-PLS), were employed to establish relationships between structural characteristics and kinase inhibitory activity of used oxindole analogs. The GA-PLS was developed as the best predictor and validated QSAR model. The data set compounds were also studied by molecular docking to investigate their binding mechanism in the active site of tyrosine kinase enzyme. According to the information obtained from QSAR models and molecular docking analysis, 40 new potent lead compounds with novel structural features were introduced. Molecular docking, drug-likeness rules, ADMET analysis, bioavailability, toxicity prediction and target identification were carried out on the newly designed oxindoles to elucidate fundamental structural properties that affect their inhibitory activity.
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