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 represents a major problem in cancer therapy. In most cases, the cross resistance profile has been shown to be accompanied by a decrease in drug accumulation in the resistant cells. At present it seems to be widely accepted that this decrease in intracellular drug levels is due to active efflux of these drugs caused by P-glycoprotein (PGP). Within the past 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-Relationship)- or QSAR (Quantitative-Structure-Activity-Relationship)-studies of modulators of MDR. The aim of this article is to review first results in this field.