title: Synthetic models related to furanocoumarin-CYP 3A4 interactions. comparison of furanocoumarin, coumarin, and benzofuran dimers as potent inhibitors of CYP3A4 activity.
abstract: Furanocoumarin derivatives (dimers and monomers) present in commercially available grapefruit juice have the capacity to inhibit the activity of human CYP3A4. Such interactions are believed to result from the mechanism-based inhibition of CYP3A4 activity in the intestine. The aim of this work was to synthesize and test a series of dimers with a view to determining the relationship between structure and inhibitory activity and determining whether they might make suitable probes of CYP3A4 activity. We prepared a series of furanocoumarin, coumarin, and benzofuran derivatives that have inhibitory effects on the activity of human CYP3A4. A synthetic benzofuran dimer, which is more accessible than furanocoumarin dimers, exhibited activity against CYP3A4 comparable to that of furanocoumarin dimers.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan. k-oda@hoku-iryo-u.ac.jp
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Oda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Teruki
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Naozumi
authors.initials: N
authors.lastname: Nishizono
mesh_terms: D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology*; D001628:Beverages / Q000032:analysis; D032083:Citrus paradisi / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011564:Furocoumarins / Q000737:chemistry* / Q000494:pharmacology*; D006900:Hydroxylation; D008956:Models, Chemical; D013739:Testosterone / Q000737:chemistry / Q000378:metabolism