title: Dihydroxybergamottin caproate as a potent and stable CYP3A4 inhibitor.
abstract: We investigated the inhibitory activity of the furanocoumarin derivatives from grapefruit juice to the drug metabolizing enzyme, cytochrome P450 (CYP) 3A4. Although two known furanocoumarin dimers GF-I-1 (1) and GF-I-4 (2) showed potent CYP3A4 inhibition with IC50 value of 0.07 microM, a semi-synthetic dihydroxybergamottin caproate (11), which was more stable and more simple than the dimers, exhibited comparable activity against CYP3A4.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, 920-0934, Kanazawa, Japan. ohta@dbs.p.kanazawa-u.ac.jp
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Ohta
authors.forename: Minoru
authors.initials: M
authors.lastname: Nagahashi
authors.forename: Shinzo
authors.initials: S
authors.lastname: Hosoi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukamoto
mesh_terms: D002208:Caproates / Q000737:chemistry / Q000494:pharmacology*; D002957:Citrus / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D002208:Caproates; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D011564:Furocoumarins; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human