Minor furanocoumarins and coumarins in grapefruit peel oil as inhibitors of human cytochrome P450 3A4.
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.
César
Thaïs B
TB
School of Pharmaceutical Sciences, University of Sao Paulo State, Araraquara, Brazil.
Manthey
John A
JA
Myung
Kyung
K
D032083:Citrus paradisi / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D006801:Humans; D007422:Intestines / Q000201:enzymology; D015394:Molecular Structure; D010938:Plant Oils / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*
C544249:6',7'-dihydroxy-7-geranyloxycoumarin; D003374:Coumarins; D065692:Cytochrome P-450 CYP3A Inhibitors; D010938:Plant Oils; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human