Oxicams, a class of nonsteroidal anti-inflammatory drugs and beyond.

Xu S, Rouzer CA, Marnett LJ
IUBMB Life. 2014 66 (12): 803-11

PMID: 25537198 · PMCID: PMC5300000 · DOI:10.1002/iub.1334

Oxicams are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) structurally related to the enolic acid class of 4-hydroxy-1,2-benzothiazine carboxamides. They are used clinically to treat both acute and chronic inflammation by inhibiting the activity of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2. Oxicams are structurally distinct from all other NSAIDs, exhibiting a novel binding pose in the COX active site. The 4-hydroxyl group on the thiazine ring partners with Ser-530 via hydrogen bonding while two coordinated water molecules mediate a polar interaction between the oxicam and COX. The rotation of Leu-531 in the complex opens a new pocket, which is not used for binding other NSAIDs to the enzyme. This structure provides the basis for understanding documented structure-activity relationships within the oxicam class. In addition, from the oxicam template, a series of potent microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors represents a new direction for drug development. Here, we review the major route of oxicam synthesis and structure-activity for COX inhibition, as well as recent advances in oxicam-mediated mPGES-1 inhibition.

© 2014 International Union of Biochemistry and Molecular Biology.

MeSH Terms (9)

Anti-Inflammatory Agents, Non-Steroidal Humans Inflammation Intramolecular Oxidoreductases Meloxicam Piroxicam Prostaglandin-E Synthases Thiazines Thiazoles

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