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Updated: Oct 8, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Structure-activity relationships of multidrug resistance reversers
1Pharmaceutical Institute, University of Bonn, Bonn, 53121, Germany. m.wiese@uni-bonn.de
Abstract:
Multidrug resistance, MDR, is a major obstacle in the chemotherapeutic treatment of cancer. MDR can be reversed by drugs that vary widely in their chemical structure and main biological action. Many efforts are directed to find out the relationships between the structure and MDR reversal effect of these drugs. In this review we try to summarize the results of a variety of studies on identification of structure-activity relationships, SARs, and quantitative SARs, QSARs, of different MDR reversing drugs. As any reasonable (Q)SAR study relies on a real or putative presentation about the mechanism of action of the studied compounds, the most significant MDR mechanisms revealed till now are shortly discussed. Special attention is paid to P-glycoprotein, P-gp, related MDR as the most experimentally and clinically tested form of drug resistance. The currently proposed models of P-gp functioning and mechanisms of MDR modulation are presented. Problems that can arise in (Q)SARs studies are discussed in advance to allow the reader to judge on possible pitfalls. The physicochemical and structural properties of MDR modulators as found by different research groups are commented and summarized. From the discussed studies it can be concluded that the careful selection of relevant structural and biological data processed with appropriate QSAR and especially 3D-QSAR methods, is a promising approach to structure-activity studies of MDR reversers.
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