Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs.

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Jain S, Tran S, El Gendy MA, Kashfi K, Jurasz P, Velazquez-Martinez CA

Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs.

J Med Chem. 2012 Jan 26;55(2):688-96. doi: 10.1021/jm200973j. Epub 2012 Jan 10.

PubMed ID
22148253 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Acetylsalicylic acidProstaglandin G/H synthase 2IC 50 (nM)2400N/AN/ADetails
IbuprofenProstaglandin G/H synthase 2IC 50 (nM)1100N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2IC 50 (nM)5700N/AN/ADetails