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

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

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 4 , 2017

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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.

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

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Article Details

Year: 2017
Page: [464 - 475]
Pages: 12
DOI: 10.2174/1570180813666160831143112
Price: $65

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