Inhibition of long chain fatty acyl-CoA synthetase (ACSL) and ischemia reperfusion injury.

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.

• Authors: Allan M Prior, Man Zhang, Nina Blakeman, Palika Datta, Hung Pham, Qian Chen, Lindon H Young, Margaret T Weis, Duy H Hua
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 24 Issue 4 Pg. 1057-61 (Feb 15 2014) ISSN: 1464-3405 [Electronic] England
• PMID: 24480468 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Coenzyme A Ligases
• long-chain-fatty-acid-CoA ligase

Topics

• Animals
• Cell Line
• Coenzyme A Ligases (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Mice
• Molecular Structure
• Reperfusion Injury (drug therapy, enzymology, metabolism)
• Structure-Activity Relationship