Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))

[Image: see text] Cytosolic phospholipase A(2) (GIVA cPLA(2)) has attracted great interest as a medicinal target because it initiates the eicosanoid cascade and is involved in a number of inflammatory diseases. As a consequence, the development of potent synthetic inhibitors is of great importance....

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Autores principales: Psarra, Anastasia, Kokotou, Maroula G., Galiatsatou, Gerasimia, Mouchlis, Varnavas D., Dennis, Edward A., Kokotos, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120731/
https://www.ncbi.nlm.nih.gov/pubmed/30197994
http://dx.doi.org/10.1021/acsomega.8b01214
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author Psarra, Anastasia
Kokotou, Maroula G.
Galiatsatou, Gerasimia
Mouchlis, Varnavas D.
Dennis, Edward A.
Kokotos, George
author_facet Psarra, Anastasia
Kokotou, Maroula G.
Galiatsatou, Gerasimia
Mouchlis, Varnavas D.
Dennis, Edward A.
Kokotos, George
author_sort Psarra, Anastasia
collection PubMed
description [Image: see text] Cytosolic phospholipase A(2) (GIVA cPLA(2)) has attracted great interest as a medicinal target because it initiates the eicosanoid cascade and is involved in a number of inflammatory diseases. As a consequence, the development of potent synthetic inhibitors is of great importance. We have developed highly potent 2-oxoester inhibitors of GIVA cPLA(2) presenting X(I)(50) values between 0.000019 and 0.000066. We demonstrate that the 2-oxoester functionality is essential for in vitro inhibitory activity, making these inhibitors useful research reagents. However, their high reactivity results in rapid degradation of the inhibitors in human plasma, limiting their pharmaceutical utility without further modification.
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spelling pubmed-61207312018-09-05 Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2)) Psarra, Anastasia Kokotou, Maroula G. Galiatsatou, Gerasimia Mouchlis, Varnavas D. Dennis, Edward A. Kokotos, George ACS Omega [Image: see text] Cytosolic phospholipase A(2) (GIVA cPLA(2)) has attracted great interest as a medicinal target because it initiates the eicosanoid cascade and is involved in a number of inflammatory diseases. As a consequence, the development of potent synthetic inhibitors is of great importance. We have developed highly potent 2-oxoester inhibitors of GIVA cPLA(2) presenting X(I)(50) values between 0.000019 and 0.000066. We demonstrate that the 2-oxoester functionality is essential for in vitro inhibitory activity, making these inhibitors useful research reagents. However, their high reactivity results in rapid degradation of the inhibitors in human plasma, limiting their pharmaceutical utility without further modification. American Chemical Society 2018-08-09 /pmc/articles/PMC6120731/ /pubmed/30197994 http://dx.doi.org/10.1021/acsomega.8b01214 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Psarra, Anastasia
Kokotou, Maroula G.
Galiatsatou, Gerasimia
Mouchlis, Varnavas D.
Dennis, Edward A.
Kokotos, George
Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))
title Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))
title_full Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))
title_fullStr Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))
title_full_unstemmed Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))
title_short Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A(2) (GIVA cPLA(2))
title_sort highly potent 2-oxoester inhibitors of cytosolic phospholipase a(2) (giva cpla(2))
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120731/
https://www.ncbi.nlm.nih.gov/pubmed/30197994
http://dx.doi.org/10.1021/acsomega.8b01214
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