The ability of gallate and pyrogallol moieties of catechins to inhibit P-glycoprotein function

Abstract

The role of structure–activity relationships in the ability of catechins to inhibit P-glycoprotein (P-gp) function was investigated with respect to gallate and pyrogallol moieties. Experiments using octyl derivatives of gallic acid indicated that the gallate moiety required the catechol group and a neighboring carbonyl group to inhibit P-gp. On the other hand, the pyrogallol moiety appeared to require three hydroxyl groups to inhibit P-gp, according to comparisons between (−)-epicatechin gallate (ECG) and (−)-epigallocatechin gallate (EGCG). The difference in the number of hydroxyl groups that gallate or pyrogallol moieties required for P-gp inhibition, was due to the presence of a carbonyl group. The P-gp inhibition by catechins was restricted by their hydrophobicity. The pyrogallol moiety of EGC did not appear to inhibit P-gp because of its low hydrophobicity. The P-gp inhibitory activity of EGCG was speculated to be increased by the addition of long carbon chains to the C3″of gallate moieties.

Keywords

• Catechin
• Gallate alkyl ester
• (−)-Epigallocatechin gallate
• P-glycoprotein
• Rhodamine-123
• Hydrophobicity