Improved Anti-inflammatory Activity and Potential Cytoprotective Properties of Tolfenamic Acid, Naproxen and Indomethacin Derivatives

Title:Improved Anti-inflammatory Activity and Potential Cytoprotective Properties of Tolfenamic Acid, Naproxen and Indomethacin Derivatives

Volume: 14 Issue: 4

Author(s): Panagiotis Theodosis-Nobelos, Theodora C. Politou, Chrysoula Athanasekou and Eleni A. Rekka

Affiliation:

Keywords: Anti-inflammatory activity, brain ischemia-reperfusion, liver injury, indomethacin, naproxen, tolfenamic acid.

Abstract: Background: Considering that inflammation is involved in many degenerative conditions, some derivatives of tolfenamic acid, naproxen and indomethacin were synthesised and evaluated biologically. They were found to possess increased anti-inflammatory activity, being more potent than the parent drugs.

Method: Thus, compound 4, the ester of naproxen with di-tert-butyl-4-(hydroxymethyl)phenol, caused about 80% reduction of carrageenan-induced rat paw oedema, much higher than that of the starting drug. The antioxidant structure containing compounds 1-4 could inhibit soybean lipoxygenase, as well as rat microsomal membrane lipid peroxidation, both effects attributed to the presence of SH or phenolic groups. The effect of compound 1, the amide of tolfenamic acid with L-cysteine ethyl ester, on paracetamol-induced oxidative liver injury and on brain oxidative stress caused by ischemia– reperfusion was examined.

Results: It was found that 1 could protect rat liver from glutathione depletion, being comparable to Nacetylcysteine, the classical antidote against paracetamol overdose, and restore hepatic function, as judged by the levels of hepatic enzymes in plasma and the microscopic examination of multiple liver slices. After cerebral ischemia, 1 reduced caspase-3 by 60% and significantly decreased the number of apoptotic cells, especially in hippocampus and cerebellum.

Cite this article as:

Theodosis-Nobelos Panagiotis, Politou C. Theodora, Athanasekou Chrysoula and Rekka A. Eleni, Improved Anti-inflammatory Activity and Potential Cytoprotective Properties of Tolfenamic Acid, Naproxen and Indomethacin Derivatives, Letters in Drug Design & Discovery 2017; 14 (4) . https://dx.doi.org/10.2174/1570180813666160831143112

DOI https://dx.doi.org/10.2174/1570180813666160831143112	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X