Inhibition of Long Chain Fatty Ccyl-CoA Synthetase (ACSL) and Ischemia Reperfusion Injury

Document Type

Article

Publication Date

2-15-2014

Abstract

Various triacsin C analogs, containing different alkenyl chains and carboxylic acid bioisoteres including 4-aminobenzoic acid, isothiazolidine dioxide, hydroxylamine, hydroxytriazene, and oxadiazolidine dione, were synthesized and their inhibitions of long chain fatty acyl-CoA synthetase (ACSL) were examined. Two methods, a cell-based assay of ACSL activity and an in situ [(14)C]-palmitate incorporation into extractable lipids were used to study the inhibition. Using an in vivo leukocyte recruitment inhibition protocol, the translocation of one or more cell adhesion molecules from the cytoplasm to the plasma membrane on either the endothelium or leukocyte or both was inhibited by inhibitors 1, 9, and triacsin C. The results suggest that inhibition of ACSL may attenuate the vascular inflammatory component associated with ischemia reperfusion injury and lead to a decrease of infarct expansion.

Publication Title

Bioorganic & Medicinal Chemistry Letters

Volume

24

Issue

4

First Page

1057

Last Page

1061

PubMed ID

24480468

Comments

This article was published in Bioorganic & Medicinal Chemistry Letters, Volume 24, Issue 4, February 15, 2014, Pages 1057-1061.

The published version is available at http://dx.doi.org/10.1016/j.bmcl.2014.01.016

Copyright © 2014 Elsevier B.V.

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