STRUCTURE-ACTIVITY-RELATIONSHIP STUDIES ON MODULATORS OF THE MULTIDRUG TRANSPORTER P-GLYCOPROTEIN - AN OVERVIEW

Resistance of tumor cells to a wide variety of cytotoxic agents repres ents a major problem in cancer therapy. In most cases, the cross resis tance profile has been shown to be accompanied by a decrease in drug a ccumulation in the resistant cells. At present it seems to be widely a ccepted that this decrease in intracellular drug levels is due to acti ve efflux of these drugs caused by P-glycoprotein (PGP). Within the pa st decade, several substances have been identified as being capable of inhibiting the active drug efflux caused by P-glycoprotein. Although many excellent reviews on the phenomenon of multidrug resistance (MDR) have been published, little is known about SAR (Structure-Activity-Re lationship)- or QSAR (Quantitative-Structure-Activity-Relationship) of modulators of MDR. The aim of this article is to review first results in this field.