Yamaguchi Yuki
School of Pharmaceutical Sciences, Health Sciences University of Hokkaido.
Yakugaku Zasshi. 2017;137(10):1209-1214. doi: 10.1248/yakushi.17-00135.
Grapefruit juice (GFJ) consumption has been shown to increase the bioavailability of certain orally administered drugs. The furanocoumarin derivatives Paradisin A and bergamottin, which are present in GFJ, are potent mechanism-based inhibitors of CYP3A4. The primary aim of this work was to synthesize a series of furanocoumarin derivatives with a view to determining the relationship between the structure of the inhibitors and their inhibitory CYP3A4 activity. Furanocoumarin derivatives that were more stable and accessible than the furanocoumarin derivatives in GFJ were prepared, and their ability to inhibit CYP3A4 was examined. Synthesized furanocoumarin monomers showed strong mechanism-based inhibition of CYP3A4. The furanocoumarin dimers are also mechanism-based inhibitors of CYP3A4. These monomers and dimers are more potent inhibitors of CYP3A4 than bergamottin and Paradisin A, respectively.
已证明饮用葡萄柚汁（GFJ）会增加某些口服药物的生物利用度。GFJ中含有的呋喃香豆素衍生物帕拉迪辛A和佛手柑内酯是CYP3A4的强效基于机制的抑制剂。这项工作的主要目的是合成一系列呋喃香豆素衍生物，以确定抑制剂结构与其抑制CYP3A4活性之间的关系。制备了比GFJ中的呋喃香豆素衍生物更稳定且更易获得的呋喃香豆素衍生物，并检测了它们抑制CYP3A4的能力。合成的呋喃香豆素单体对CYP3A4表现出强烈的基于机制的抑制作用。呋喃香豆素二聚体也是CYP3A4的基于机制的抑制剂。这些单体和二聚体分别比佛手柑内酯和帕拉迪辛A对CYP3A4的抑制作用更强。
