Dihydroxybergamottin caproate as a potent and stable CYP3A4 inhibitor

Bioorg Med Chem. 2002 Apr;10(4):969-73. doi: 10.1016/s0968-0896(01)00362-5.

Abstract

We investigated the inhibitory activity of the furanocoumarin derivatives from grapefruit juice to the drug metabolizing enzyme, cytochrome P450 (CYP) 3A4. Although two known furanocoumarin dimers GF-I-1 (1) and GF-I-4 (2) showed potent CYP3A4 inhibition with IC50 value of 0.07 microM, a semi-synthetic dihydroxybergamottin caproate (11), which was more stable and more simple than the dimers, exhibited comparable activity against CYP3A4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caproates / chemistry
  • Caproates / pharmacology*
  • Citrus / chemistry
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors*
  • Drug Stability
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Furocoumarins / chemistry
  • Furocoumarins / pharmacology*
  • Inhibitory Concentration 50
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Caproates
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Furocoumarins
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human