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Communication | Regular issue | Vol 71, No. 1, 2007, pp.1-4
Published online, 1st December, 2006
DOI: 10.3987/COM-06-10873
■ Synthetic Models Related to Furanocoumarin-CYP 3A4 Interactions. Synthesis of Furanocoumarin Derivatives as Potent Inhibitors of CYP 3A4

Kazuaki Oda,* Yukio Tamai, Yuki Yamaguchi, Teruki Yoshimura, Keiji Wada, Minoru Machida, and Naozumi Nishizono*

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

We prepared a series of furanocoumarin derivatives that have inhibitory effects on the activity of human cytochrome P450 (CYP) 3A4. The reported furanocoumarin dimers paradisins A and B from grapefruit juice showed potent CYP 3A4 inhibition with an IC50 value of 0.07 μM. Synthetic furanocoumarin derivatives, which are more stable and accessible than paradisins, exhibited comparable activity against CYP 3A4.