Effect of structural modification on the inhibitory selectivity of rutaecarpine derivatives on human CYP1A1, CYP1A2, and CYP1B1

Bioorg Med Chem Lett. 2003 Aug 4;13(15):2535-8. doi: 10.1016/s0960-894x(03)00469-4.

Abstract

Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inhibitors. 1-Methoxyrutaecarpine and 1,2-dimethoxyrutaecarpine are the most selective CYP1A2 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
  • Binding Sites / drug effects
  • Cytochrome P-450 CYP1A1 / antagonists & inhibitors*
  • Cytochrome P-450 CYP1A2 Inhibitors*
  • Cytochrome P-450 CYP1B1
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Indole Alkaloids
  • Models, Molecular
  • Molecular Conformation
  • Quinazolines
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Enzyme Inhibitors
  • Indole Alkaloids
  • Quinazolines
  • rutecarpine
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1B1