Minor furanocoumarins and coumarins in grapefruit peel oil as inhibitors of human cytochrome P450 3A4

Thaïs B César; John A Manthey; Kyung Myung

doi:10.1021/np900266m

Minor furanocoumarins and coumarins in grapefruit peel oil as inhibitors of human cytochrome P450 3A4

J Nat Prod. 2009 Sep;72(9):1702-4. doi: 10.1021/np900266m.

Authors

Thaïs B César¹, John A Manthey, Kyung Myung

Affiliation

¹ School of Pharmaceutical Sciences, University of Sao Paulo State, Araraquara, Brazil.

PMID: 19689106
DOI: 10.1021/np900266m

Abstract

A new cyclic acetal (1) of marmin (6',7'-dihydroxy-7-geranyloxycoumarin), two new cyclic acetals (5, 6) of 6',7'-dihydroxybergamottin, and the known compounds marmin (2), 7-geranyloxycoumarin (3), bergamottin (4), and 6',7'-dihydroxybergamottin (7) were isolated from grapefruit peel oil. All compounds were tested for inhibitory activity against intestinal cytochrome P450 3A4, an enzyme involved in the "grapefruit/drug" interactions in humans. Coumarins (1-3) exhibited negligible inhibitory activity, while the furanocoumarins (4-7) showed potent in vitro inhibitory activity with IC(50) values of 2.42, 0.13, 0.27, and 1.58 microM, respectively.

MeSH terms

Citrus paradisi / chemistry*
Coumarins / chemistry
Coumarins / isolation & purification*
Coumarins / pharmacology*
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP3A Inhibitors*
Humans
Intestines / enzymology
Molecular Structure
Plant Oils / chemistry
Plants, Medicinal / chemistry*

Substances

6',7'-dihydroxy-7-geranyloxycoumarin
Coumarins
Cytochrome P-450 CYP3A Inhibitors
Plant Oils
Cytochrome P-450 CYP3A
CYP3A4 protein, human