Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14alpha-demethylase (CYP51).

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.

• Authors: Tina Korosec, Jure Acimovic, Matej Seliskar, Darko Kocjan, Klementina Fon Tacer, Damjana Rozman, Uros Urleb
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 1 Pg. 209-21 (Jan 01 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 17964172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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