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

Tina Korošec; Jure Ačimovič; Matej Seliškar; Darko Kocjan; Klementina Fon Tacer; Damjana Rozman; Uroš Urleb

doi:10.1016/j.bmc.2007.10.001

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

Tina Korošec, Jure Ačimovič, Matej Seliškar, Darko Kocjan, Klementina Fon Tacer, Damjana Rozman, Uroš Urleb

Physiology

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	209-221
Number of pages	13
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.bmc.2007.10.001
State	Published - Jan 1 2008

Keywords

Cholesterol biosynthesis inhibitors
Cholesterol intermediates profile
Human lanosterol 14α-demethylase (CYP51) inhibitors
Pyridylethanolamines

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmc.2007.10.001

Cite this

@article{0a0cbc290b87416ba8908fb529095ff8,

title = "Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14α-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 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.",

keywords = "Cholesterol biosynthesis inhibitors, Cholesterol intermediates profile, Human lanosterol 14α-demethylase (CYP51) inhibitors, Pyridylethanolamines",

author = "Tina Koro{\v s}ec and Jure A{\v c}imovi{\v c} and Matej Seli{\v s}kar and Darko Kocjan and Tacer, {Klementina Fon} and Damjana Rozman and Uro{\v s} Urleb",

note = "Funding Information: This work was supported by the funds from Lek Pharmaceuticals d. d., Slovenian Research Agency Grants L-6707, J1-6713, and P1-0527, the ESSR supported activity Center of Excellence—Biotechnology with Pharmacy, and by European Community (STEROLTALK Project No. LSHG-CT-2005-512096). Matej Seli{\v s}kar and Klementina Fon Tacer were supported by fellowships from Slovenian Research Agency. We thank Mogens Baltsen and Dr. A.G. Byskov (Laboratory of Reproductive Biology, University Hospital of Copenhagen) for FF-MAS and T-MAS and Prof. Dr. M.R. Waterman (Institute of Biochemistry, Medical Faculty, Vanderbilt University, Nashville, TN) for the human CYP51 expression plasmid. ",

year = "2008",

month = jan,

day = "1",

doi = "10.1016/j.bmc.2007.10.001",

language = "English (US)",

volume = "16",

pages = "209--221",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "1",

}

TY - JOUR

T1 - Novel cholesterol biosynthesis inhibitors targeting human lanosterol 14α-demethylase (CYP51)

AU - Korošec, Tina

AU - Ačimovič, Jure

AU - Seliškar, Matej

AU - Kocjan, Darko

AU - Tacer, Klementina Fon

AU - Rozman, Damjana

AU - Urleb, Uroš

N1 - Funding Information: This work was supported by the funds from Lek Pharmaceuticals d. d., Slovenian Research Agency Grants L-6707, J1-6713, and P1-0527, the ESSR supported activity Center of Excellence—Biotechnology with Pharmacy, and by European Community (STEROLTALK Project No. LSHG-CT-2005-512096). Matej Seliškar and Klementina Fon Tacer were supported by fellowships from Slovenian Research Agency. We thank Mogens Baltsen and Dr. A.G. Byskov (Laboratory of Reproductive Biology, University Hospital of Copenhagen) for FF-MAS and T-MAS and Prof. Dr. M.R. Waterman (Institute of Biochemistry, Medical Faculty, Vanderbilt University, Nashville, TN) for the human CYP51 expression plasmid.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

KW - Cholesterol biosynthesis inhibitors

KW - Cholesterol intermediates profile

KW - Human lanosterol 14α-demethylase (CYP51) inhibitors

KW - Pyridylethanolamines

UR - http://www.scopus.com/inward/record.url?scp=38049161752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38049161752&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2007.10.001

DO - 10.1016/j.bmc.2007.10.001

M3 - Article

C2 - 17964172

AN - SCOPUS:38049161752

SN - 0968-0896

VL - 16

SP - 209

EP - 221

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this