Dihydroxybergamottin caproate as a potent and stable CYP3A4 inhibitor.
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.
Ohta
Tomihisa
T
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, 920-0934, Kanazawa, Japan. ohta@dbs.p.kanazawa-u.ac.jp
Nagahashi
Minoru
M
Hosoi
Shinzo
S
Tsukamoto
Sachiko
S
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
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