N-水杨酰芳胺衍生物抗肿瘤活性的3D-QSAR研究

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摘要基于比较分子场分析(CoMFA)方法研究N-水杨酰芳胺衍生物对四种癌细胞(包括A549、MCF-7、SGC-7901和Bel-7402)的抗肿瘤活性(pHi, i = 1, 2, 3, 4)的三维定量构效关系(3D-QSAR)。训练集中12个化合物用于建立预测模型，测试集5个化合物(含模板分子)作为模型验证。上述模型中立体场和静电场对pH1、pH2、pH3和pH4的贡献率依次为23.8%和76.2%、20.1%和79.9%、18.7%和81.3%、14.3%和85.7%。它们的交叉验证系数(Rcv2)和非交叉验证系数(R2)相应为0.826和0.963、0.867和0.974、0.941和0.989、0.797和0.961，说明所建模型具有较强的稳定性和良好的预测能力。基于CoMFA等势图揭示了影响这些化合物抗癌活性的关键结构因素。本文研究结果为理解其抗肿瘤作用机理、设计具有高抗肿瘤活性的N-水杨酰芳胺衍生物并预测它们活性提供了理论参考。

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	冯慧
	冯长君

关键词 ： N-aryl-salicylamide derivatives, anti-tumor activity, 3D-QSAR, CoMFA

Abstract：In the present work, comparative molecular field analysis (CoMFA) techniques were used to perform three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on the anti-tumor activity (pHi, i = 1, 2, 3, 4) of N-aryl-salicylamide derivatives against four cancer cell lines, including A549, MCF-7, SGC-7901, and Bel-7402. 12 compounds were randomly selected as the training set to establish the prediction models, which were verified by the test set of 5 compounds containing template molecule. The contributions of steric and electrostatic fields to pH1, pH2, pH3, and pH4 were 23.8% and 76.2%, 20.1% and 79.9%, 18.7% and 81.3%, and 14.3% and 85.7%, respectively. The cross-validation (Rcv2) and non-cross-validation coefficients (R2) were 0.826 and 0.963 for pH1, 0.867 and 0.974 for pH2, 0.941 and 0.989 for pH3, and 0.797 and 0.961 for pH4, respectively. The CoMFA models were then used to predict the activities of the compounds, and it was found that the models had strong stability and good predictability. Based on the CoMFA contour maps, some key structural factors responsible for the anticancer activity of the series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new N-aryl-salicylamide derivatives with high anti-tumor activity, and predicting their activities.

Key words： N-aryl-salicylamide derivatives anti-tumor activity 3D-QSAR CoMFA

收稿日期: 2019-03-20 出版日期: 2019-10-30

基金资助:This project was supported by the National Natural Science Foundation of China (21075138) and the special fund of State Key Laboratory of Structural Chemistry (20160028)

通讯作者: fengcj@xzit.edu.cn E-mail: fengcj@xzit.edu.cn

引用本文:

冯慧;冯长君. N-水杨酰芳胺衍生物抗肿瘤活性的3D-QSAR研究[J]. 结构化学, 2019, 38(11): 1874-1880.
FENG Hui;FENG Chang-Jun. 3D-QSAR Studies on the Anti-tumor Activity of N-Aryl-salicylamide Derivatives. CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2019, 38(11): 1874-1880.

链接本文:

http://manu30.magtech.com.cn/jghx/CN/ 或 http://manu30.magtech.com.cn/jghx/CN/Y2019/V38/I11/1874

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