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

Tina Korosec; Jure Acimovic; Matej Seliskar; Darko Kocjan; Klementina Fon Tacer; Damjana Rozman; Uros Urleb

doi:10.1016/j.bmc.2007.10.001

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.

Authors

Tina Korosec¹, Jure Acimovic, Matej Seliskar, Darko Kocjan, Klementina Fon Tacer, Damjana Rozman, Uros Urleb

Affiliation

¹ Lek Pharmaceuticals d. d., Drug Discovery, 1000 Ljubljana, Verovskova 57, Slovenia.

PMID: 17964172
DOI: 10.1016/j.bmc.2007.10.001

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