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Inhibitors of Microsomal Prostaglandin E 2 Synthase‐1 Enzyme as Emerging Anti‐Inflammatory Candidates
Author(s) -
Singh Bahia Malkeet,
Kumar Katare Yogesh,
Silakari Om,
Vyas Bhawna,
Silakari Pragati
Publication year - 2014
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21306
Subject(s) - prostacyclin , prostaglandin , thromboxane , prostaglandin e , chemistry , pharmacology , prostaglandin h2 , enzyme , microsome , thromboxane a synthase , thromboxane a2 , arachidonic acid , atp synthase , biosynthesis , eicosanoid , cyclooxygenase , biochemistry , receptor , medicine , platelet
Cyclooxygenases (COX‐1 and COX‐2) catalyze the conversion of arachidonic acid (AA) into PGH 2 that is further metabolized by terminal prostaglandin (PG) synthases into biologically active PGs, for example, prostaglandin E 2 (PGE 2 ), prostacyclin I 2 (PGI 2 ), thromboxane A 2 (TXA 2 ), prostaglandin D 2 (PGD 2 ), and prostaglandin F 2 alpha (PGF 2α ). Among them, PGE 2 is a widely distributed PG in the human body, and an important mediator of inflammatory processes. The successful modulation of this PG provides a beneficial strategy for the potential anti‐inflammatory therapy. For instance, nonsteroidal anti‐inflammatory agents (NSAIDs), both classical nonselective ( c NSAIDs) and the selective COX‐2 inhibitors (coxibs) attenuate the generation of PGH 2 from AA that in turn reduces the synthesis of PGE 2 and modifies the inflammatory conditions. However, the long‐term use of these agents causes severe side effects due to the nonselective inhibition of other PGs, such as PGI 2 and TXA 2 , etc. Microsomal prostaglandin E 2 synthase‐1 (mPGES‐1), a downstream PG synthase, specifically catalyzes the biosynthesis of COX‐2‐derived PGE 2 from PGH 2 , and describes itself as a valuable therapeutic target for the treatment of acute and chronic inflammatory disease conditions. Therefore, the small molecule inhibitors of mPGES‐1 would serve as a beneficial anti‐inflammatory therapy, with reduced side effects that are usually associated with the nonselective inhibition of PG biosynthesis.

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