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Updated: May 26, 2026

En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs
Sarthak Jain1, Susan Tran, Mohamed A M El Gendy
1Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8 Canada.
Abstract:
The objective of this work was to evaluate the biological properties of a new series of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) possessing a tyrosol linker between the NSAID and the NO-releasing moiety (PROLI/NO); however, initial screening of ester intermediates without the PROLI/NO group showed the required (desirable) efficacy/safety ratio, which questioned the need for NO in the design. In this regard, NSAID ester intermediates were potent and selective COX-2 inhibitors in vitro, showed equipotent anti-inflammatory activity compared to the corresponding parent NSAID, but showed a markedly reduced gastric toxicity when administered orally. These results provide complementary evidence to challenge the currently accepted notion that hybrid NO-NSAIDs exert their cytoprotective effects by releasing NO. Results obtained in this work constitute a good body of evidence to initiate a debate about the future replacement of NSAID prodrugs for unprotected NSAIDs (possessing a free carboxylic acid group) currently in clinical use.
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