A Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) of Anthranilamide Derivatives That Are Multidrug Resistance Modulators

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• 作者：Philippe Labrie ; Shawn P. Maddaford ; Sebastien Fortin ; Suman Rakhit ; Lakshmi P. Kotra ; and ; René ; C. Gaudreault
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：December 28, 2006
• 年：2006
• 卷：49
• 期：26
• 页码：7646 - 7660
• 全文大小：619K
• 年卷期：v.49,no.26(December 28, 2006)
• ISSN：1520-4804

文摘

In a continuing effort to develop potent and selective modulators of P-glycoprotein (P-gp) activity overcomingthe chemoresistance acquired by tumor cells during cancer chemotherapy, we developed 3D quantitativestructure-activity relationship (3D QSAR) models using CoMFA and CoMSIA analyses. This study correlatesthe P-glycoprotein inhibitory activities of 49 structurally related anthranilamide derivatives to severalphysicochemical parameters representing steric, electrostatic, acceptor, donor, and hydrophobic fields. BothCoMFA and CoMSIA models using three different alignment conformations gave good internal predictions,and their cross-validated r² values are between 0.503 and 0.644. These most comprehensive CoMFA andCoMSIA models are useful in understanding the structure-activity relationships of anthranilamide derivativesas well as aid in the design of novel derivatives with enhanced modulation of P-gp activity.