title: Biotransformations of 6',7'-dihydroxybergamottin and 6',7'-epoxybergamottin by the citrus-pathogenic fungi diminish cytochrome P450 3A4 inhibitory activity.
abstract: Penicillium digitatum, as well as five other citrus pathogenic species, (Penicillium ulaiense Link, Geotrichum citri Link, Botrytis cinerea P. Micheli ex Pers., Lasiodiplodia theobromae (Pat.) Griffon & Maubl., and Phomopsis citri (teleomorph Diaporthe citri)) were observed to convert 6',7'-epoxybergamottin (1) into 6',7'-dihydroxybergamottin (2), bergaptol (3), and an opened lactone ring metabolite 6,7-furano-5-(6',7'-dihydroxy geranyloxy)-2-hydroxy-hydrocoumaric acid (4). Metabolism of 2 by these fungi also proceeded to 4. The structure of 4 was established by high resolution mass spectrometry and (1)H and (13)C NMR techniques. The inhibitory activity of 4 towards human intestinal cytochrome P450 3A4 (CYP3A4) was greatly decreased (IC(50) >172.0 μM) compared to 2 (IC(50)=0.81 μM).
authors.affiliation: US Horticultural Research Laboratory, Agricultural Research Service, US Department of Agriculture, Fort Pierce, FL 34945, USA. Kmyung@dow.com
authors.forename: Kyung
authors.initials: K
authors.lastname: Myung
authors.forename: John A
authors.initials: JA
authors.lastname: Manthey
authors.forename: Jan A
authors.initials: JA
authors.lastname: Narciso
mesh_terms: D001628:Beverages; D001711:Biotransformation; D032083:Citrus paradisi / Q000737:chemistry* / Q000382:microbiology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D005524:Food Technology; D005658:Fungi / Q000378:metabolism*; D011564:Furocoumarins / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D011564:Furocoumarins; C475527:epoxybergamottin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C080771:bergaptol; C104774:6',7'-dihydroxybergamottin