Marine natural products with P-glycoprotein inhibitor properties

Abstract

P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters.

Figure 1

Flippase mechanism. P-gp interchanges molecules from the inner leaflet of the membrane to the outer leaflet, in order to maintain a concentration balance on both sides.

Figure 2

Hydrophobic vacuum cleaner mechanism. (1) Substrates pass through the membrane to the lipid bilayer; (2) substrates can enter the P-gp through “portals” that pass the substrate from the lipid bilayer in to the P-gp internal cavity; (3) substrates bind to the drug-binding site (DBS); (4) P-gp transports the substrate to the outside of the cell.

Figure 3

Inhibitors of P-gp that have been isolated from tunicates.

Figure 4

Inhibitors of P-gp that have been isolated from sponges.

Figure 5

Inhibitors of P-gp that have been isolated from cyanobacteria and algae.

Figure 6

Inhibitors of P-gp that have been isolated from bryozoans, corals and marine bacteria.