Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method

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摘要 A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was conducted to analyze the A1AR density (Bmax) of 56 3-aroyl-5-substituted thiophene derivatives (ASTDs) in human A1 Chinese hamster ovary (hA1CHO) membranes by the comparative molecular field analysis (CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation (Rcv2) and non-cross-validation (R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.

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	冯惠
	冯长君
	曹景沛

关键词 ： 3-aroyl-5-substituted thiophene derivatives (ASTDs), A1AR density (Bmax), three-dimensional quantitative structure-activity relationship, comparative molecular field analysis

Abstract：A three-dimensional quantitative structure-activity relationship (3D-QSAR) study was conducted to analyze the A1AR density (Bmax) of 56 3-aroyl-5-substituted thiophene derivatives (ASTDs) in human A1 Chinese hamster ovary (hA1CHO) membranes by the comparative molecular field analysis (CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation (Rcv2) and non-cross-validation (R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.

Key words： 3-aroyl-5-substituted thiophene derivatives (ASTDs) A1AR density (Bmax) three-dimensional quantitative structure-activity relationship comparative molecular field analysis

收稿日期: 2019-12-17 出版日期: 2020-11-09

基金资助:This project was supported by the National Natural Science Foundation of China (21676292, 21075138) and special fund of State Key Laboratory of Structure Chemistry (2016028)

通讯作者: caojingpei@cumt.edu.cn E-mail: caojingpei@cumt.edu.cn

引用本文:

冯惠;冯长君;曹景沛. Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method[J]. 结构化学, 2020, 39(11): 1978-1984.
FENG Hui;FENG Chang-Jun;CAO Jing-Pei. Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method. CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2020, 39(11): 1978-1984.

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http://manu30.magtech.com.cn/jghx/CN/ 或 http://manu30.magtech.com.cn/jghx/CN/Y2020/V39/I11/1978

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