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Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A₂ (GIVA cPLA₂).

ABSTRACT: Cytosolic phospholipase A₂ (GIVA cPLA₂) 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 cPLA₂ 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.

SUBMITTER: Psarra A

PROVIDER: S-EPMC6120731 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A2 (GIVA cPLA2).

Psarra Anastasia A Kokotou Maroula G MG Galiatsatou Gerasimia G Mouchlis Varnavas D VD Dennis Edward A EA Kokotos George G

ACS omega 20180809 8

Cytosolic phospholipase A2 (GIVA cPLA2) 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 cPLA2 presenting XI(50) values between 0.000019 and 0.000066. We demonstrate that the 2-oxoester functionalit ...[more]

PMID: 30197994

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