Flavonoids: An Emerging Lead in the P-glycoprotein Inhibition

Abstract

Multidrug resistance is a major obstacle in cancer chemotherapy. Cancer cells efflux chemotherapeutic drug out of cell by means of transporter and reduce the active concentration of it inside cell. Such transporters are member of the ATP binding cassettes (ABC) protein. It includes P-gp, multiple resistant protein (MRP), and breast cancer resistant protein (BCRP). These proteins are widely distributed in the human cells such as kidney, lung, endothelial cells of blood brain barrier etc. However, there are number of drugs developed for it, but most of them are getting transported by it. So, still there is necessity of a good modulator, which could effectively combat the transport of chemotherapeutic agents. Natural products origin modulators were found to be effective against transporter such as flavonoids, which belongs to third generation modulators. They have advantage over synthetic inhibitor in the sense that they have simple structure and abundant in nature. This review focuses on the P-gp structure its architecture, efflux mechanism, herbal inhibitors and their mechanism of action.

Quantitative Structure–Activity Relationships for the Flavonoid-Mediated Inhibition of P-Glycoprotein in KB/MDR1 Cells

“…Given the role of P-gp in influencing cancer chemotherapy, methods to overcome P-gp-mediated efflux have been investigated. It is generally believed that the mechanisms of P-gp inhibition mainly comprise four aspects: competitively, non-competitively or allosterically blocking the drug binding site; interfering with the ATP hydrolysis process; altering the integrity of cell membrane lipids; decreasing the P-gp expression [1]. Four generations of P-gp inhibitors have been identified in recent years.…”