Novel Cholesterol Biosynthesis Inhibitors Targeting Human Lanosterol 14alpha-demethylase (CYP51)

Bioorg Med Chem. 2008 Jan 1;16(1):209-21. doi: 10.1016/j.bmc.2007.10.001. Epub 2007 Oct 4.

Abstract

Novel cholesterol biosynthesis inhibitors, a group of pyridylethanol(phenylethyl)amine derivatives, were synthesized. Sterol profiling assay in the human hepatoma HepG2 cells revealed that compounds target human lanosterol 14alpha-demethylase (CYP51). Structure-activity relationship study of the binding with the overexpressed human CYP51 indicates that the pyridine binds within the heme binding pocket in an analogy with the azoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / chemical synthesis
  • Anticholesteremic Agents / pharmacology*
  • Binding Sites
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Cholesterol / biosynthesis
  • Cytochrome P-450 Enzyme Inhibitors*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Oxidoreductases / antagonists & inhibitors*
  • Pyridines / chemical synthesis
  • Pyridines / pharmacology*
  • Sterol 14-Demethylase
  • Structure-Activity Relationship

Substances

  • Anticholesteremic Agents
  • CYP51A1 protein, human
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Pyridines
  • Cholesterol
  • Oxidoreductases
  • Sterol 14-Demethylase