ABCB1 in the ABC transporter family also termed as P-glycoprotein, grants the simultaneous resistance of metastatic cancer cells towards various anti-cancer drugs with different targets and diverse chemical structures. For the past four decades, researchers have tried to search for safe and specific inhibitors of this pump. Naturally occurring flavonoids as benzopyrone derivatives are an example of non-toxic inhibitors of P-gp. In reversing multidrug resistance both in vitro and in vivo, the recent advent of synthetic flavonoid dimer FD18, as a potent P-gp modulator plays is also known. FD18 specifically targets the pseudodimeric structure of the drug transporter. These molecules represent a new generation of inhibitors with high transporter binding affinity and low toxicity.
This review focuses upon the current updates on the structure-activity relationships of flavonoids, the molecular mechanisms of their action and their ability to overcome P-gp-mediated MDR in preclinical studies. It presents crucial implications on the discovery of new drug candidates that modulated the efflux of ABC transporters and also provides some clues for the future development of flavonoid based pharmaceuticals that act as P-gp inhibitors.