Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14alpha-demethylase (CYP51).
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.
Korosec
Tina
T
Lek Pharmaceuticals d. d., Drug Discovery, 1000 Ljubljana, Verovskova 57, Slovenia.
Acimovic
Jure
J
Seliskar
Matej
M
Kocjan
Darko
D
Tacer
Klementina Fon
KF
Rozman
Damjana
D
Urleb
Uros
U
D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D058886:Sterol 14-Demethylase; D013329:Structure-Activity Relationship
D000924:Anticholesteremic Agents; C548418:CYP51A1 protein, human; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D011725:Pyridines; D002784:Cholesterol; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase