Designing of Drug Molecules for Reversing PGlycoprotein (P-gp) Mediated Drug Resistance in Cancer Cells

Multidrug resistance in cancer mediated by the efflux pump P-glycoprotein is seriously hindering the cancer chemotherapy. Many selective and potent compounds of P-gp inhibitors have been identified and are undergoing clinical trials, but none of them are clinically active. Extensive search for MDR modulator has identified naturally occurring acridone alkaloid having potential to overcome drug resistance because of its unique characteristics and mechanism. Later acridone carboxamide (GF120918), Imidazo acridone (C1311) and trimethylene acridone derivative 1,3-bis(9-oxoacridin-10- yl)-propane (PBA) were identified as compounds having potential to overcome P-gp mediated cancer. N10-substituted acridones have drawn much attention in selectively inhibiting P-gp and other transporters of ABC super family.

Here we try to summarize the recent advances concerned to multidrug resistance in highlighting the structural features of P-gp substrates or inhibitors, contribution of natural products, peptides, nanotechnology, mathematical and computational strategies. This chapter envisages the various drugs being developed for treating MDR in cancer cells and especially the acridone derivatives which are being developed by the author himself in the last decade based on the research that has happened in the field of MDR in cancer.

Keywords: Acridones, Calmodulin, Multi Drug Resistance (MDR), Multi-drug Resistance associated Protein (MRP), P-glycoprotein (P-gp).