Defying Multidrug Resistance! Modulation of Related Transporters by Flavonoids and Flavonolignans

Multidrug resistance (MDR) is a major challenge for the 21th century in both cancer chemotherapy and antibiotic treatment of bacterial infections. Efflux pumps and transport proteins play an important role in MDR. Compounds displaying inhibitory activity toward these proteins are prospective for adjuvant treatment of such conditions. Natural low-cost and nontoxic flavonoids, thanks to their vast structural diversity, offer a great pool of lead structures with broad possibility of chemical derivatizations. Various flavonoids were found to reverse both antineoplastic and bacterial multidrug resistance by inhibiting Adenosine triphosphate Binding Cassette (ABC)-transporters (human P-glycoprotein, multidrug resistance-associated protein MRP-1, breast cancer resistance protein, and bacterial ABC transporters), as well as other bacterial drug efflux pumps: major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), small multidrug resistance (SMR) and resistance-nodulation-cell-division (RND) transporters, and glucose transporters. Flavonoids and particularly flavonolignans are therefore highly prospective compounds for defying multidrug resistance.