Synthesis and biological evaluation of 6′, 7′-dihydroxybergamottin (6, 7-DHB), a naturally occurring inhibitor of cytochrome P450 3A4

…, PM Woster, DJ Edwards, K He, PF Hollenberg

Index: Bellevue III, Frank H.; Woster, Patrick M.; Edwards, David J.; He, Kan; Hollenberg, Paul F. Bioorganic and Medicinal Chemistry Letters, 1997 , vol. 7, # 20 p. 2593 - 2598

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Citation Number: 25

Abstract

The recently isolated inhibitor of cytochrome P450 CYP3A4, 6′, 7′-dihydroxybergamottin (6, 7-DHB), was synthesized by an efficient route that is readily adaptable to the production of analogues. The compound was evaluated as an inhibitor of 3A4 in a purified enzyme preparation, as well as against human liver microsomes and human 3A4 expressed in Escherichia coli membrane. In each case, 6, 7-DHB proved to be a potent NADPH-and ...