Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14α-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 14α-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.

Novel pyridylethanol(phenylethyl)amines were synthesized and screened for cholesterol biosynthesis inhibition in the human hepatoma HepG2 cell assay. The compounds inhibit cholesterol biosynthesis by targeting lanosterol 14α-demethylase (CYP51). SAR of the binding with the overexpressed human CYP51 indicates that the pyridine binds within the heme binding pocket in analogy with the azoles.Figure optionsDownload as PowerPoint slide