Format

Send to:

Choose Destination

PubMed Citations for PubChem BioAssay (Select 648864)

See comment in PubMed Commons below
J Med Chem. 2012 Jan 26;55(2):688-96. doi: 10.1021/jm200973j. Epub 2012 Jan 10.

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

Author information

  • 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.

PMID:
22148253
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk