Nitric oxide releasing derivatives of tolfenamic acid with anti-inflammatory activity and safe gastrointestinal profile

Bioorg Med Chem. 2005 Dec 1;13(23):6485-92. doi: 10.1016/j.bmc.2005.07.049. Epub 2005 Sep 26.

Abstract

Tolfenamic acid esters with nitrooxyalcohols are synthesized. They are anti-inflammatory agents reducing carrageenan rat paw edema, with low gastrointestinal and general toxicity. In vitro, they are nitric oxide donors, inhibitors of lipoxygenase and cyclooxygenases. A two to three carbon chain between carboxylic and nitric ester groups seems optimal for activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Female
  • Hindlimb / drug effects
  • Intestines / drug effects*
  • Isoenzymes / metabolism
  • Lipoxygenase / metabolism
  • Male
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Rats
  • Stomach / drug effects*
  • ortho-Aminobenzoates / adverse effects
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Enzyme Inhibitors
  • Isoenzymes
  • ortho-Aminobenzoates
  • Nitric Oxide
  • tolfenamic acid
  • Lipoxygenase
  • Cyclooxygenase 1
  • Cyclooxygenase 2