| Abstract
| - 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.
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