| Identification of 2-mercaptohexanoic acids as dual inhibitors of 5-lipoxygenase and microsomal prostaglandin E(2) synthase-1. | |
| | |
MedLine Citation:
|
PMID: 21570310 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
5-Lipoxygenase (5-LO) and microsomal prostaglandin E(2) synthase (mPGES)-1 are key enzymes in the biosynthesis of leukotrienes and prostaglandin (PG)E(2), respectively, and are considered as valuable targets for the treatment of inflammatory diseases. Here, we present the identification of 2-mercaptohexanoic acid derivatives as dual inhibitors of 5-LO and mPGES-1. The lead compound 2(4-(3-biphenyloxypropoxy)phenylthio)hexanoic acid (21) inhibits human 5-LO and mPGES-1 in cell-free assays with an IC(50)=3.5 and 2.2μM, respectively, and suppresses 5-LO in intact cells with even a higher potency (IC(50)=0.9μM). Compound 21 (10μM) neither significantly inhibited the related 12- or 15-LOs nor cyclooxygenase-1 and -2 or cytosolic phospholipase A(2). Based on the selective and potent inhibition of 5-LO and mPGES-1, further assessment of these 2-mercaptohexanoic acids in preclinical models of inflammation are warranted. |
| | |
Authors:
|
Christine Greiner; Heiko Zettl; Andreas Koeberle; Carlo Pergola; Hinnak Northoff; Manfred Schubert-Zsilavecz; Oliver Werz |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-4-22 |
Journal Detail:
|
Title: Bioorganic & medicinal chemistry Volume: - ISSN: 1464-3391 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-5-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier Ltd. |
Affiliation:
|
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as se...
Next Document: Studies for the application of boron neutron capture therapy to the treatment of differentiated thyr...