ARS | Publication request: Minor furanocoumarins and coumarins in grapefruit peel oil as inhibitors of human cytochrome P450 3A4

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 29, 2009
Publication Date: August 18, 2009
Citation: Cesar, T.B., Manthey, J.A., Myung, K. 2009. Minor furanocoumarins and coumarins in grapefruit peel oil as inhibitors of human cytochrome P450 3A4. Journal of Natural Products. 72:1702-1704.

Interpretive Summary: Three new compounds were isolated and chemically characterized from grapefruit peel oil residues. These compounds were hydrophobic analogs of furanocoumarins and coumarins normally found in grapefruit juice. These compounds were strong inhibitors of the human intestinal enzyme that is responsible for the "grapefruit-drug interactions".

Technical Abstract: A novel cyclic acetal of 6',7'-dihydroxy-7-geranyloxycoumarin (marmin) and two novel cyclic acetals of 6',7'-dihydroxybergamottin were isolated from nonvolatile residues of grapefruit peel oil. Other known compounds, marmin, 7-geranyloxycoumarin, bergamottin, and 6',7'-dihydroxybergamottin were also isolated. All compounds were tested for inhibitory activity against cytochrome P450 3A4, an enzyme involved in the "grapefruit/drug" interactions in humans. Coumarins exhibited negligible inhibitory activity, while the furanocoumarins showed potent in vitro inhibitory activity with IC50 values of 0.587, 0.063, 0.139, and 0.819 µg/mL, respectively.