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

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 time dependent inactivator of 3A4.