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  • http://hdl.handle.net/10402/era.25013
  • NSAID Prodrugs with Improved Anti-inflammatory Activity and Low Ulcerogenicity: Wake Up Call to Pharmaceutical Companies and Health Authorities
  • Jain, Sarthak
  • English
  • NSAIDs
    gastric toxicity
    Nitric Oxide
    tyrosol
    Ulcerogenicity
  • Jan 10, 2012 11:09 AM
  • Thesis
  • English
  • Adobe PDF
  • 2198601 bytes
  • The objective of this work was to synthesize and evaluate the biological properties of a new series of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) possessing a tyrosol linker between the carboxylic acid present in classical NSAIDs and a NO-releasing group (PROLI/NO) derived from the naturally occurring amino acid L-proline; however, initial screening of ester intermediates without the PROLI/NO group showed the desired efficacy/safety ratio. The NSAID prodrugs were potent selective COX-2 inhibitors and showed equipotent anti-inflammatory activity compared to the corresponding parent NSAIDs, but showed a markedly reduced gastric toxicity. Furthermore, simple NSAID ester prodrugs were able to increase the activity of phase II carcinogen-metabolizing enzymes (NQO1); however, unlike NCX-4016 (NO-aspirin), NSAID esters were not effective inhibitors of platelet aggregation. These results provide complementary evidence to assume that the use of NO-releasing groups in hybrid NSAID prodrugs is not required to decrease the ulcerogenic profile of classical NSAIDs.
  • Master's
  • Master of Science
  • Faculty of Pharmacy and Pharmaceutical Sciences
  • Spring 2012
  • Carlos A Velázquez (Faculty of Pharmacy and Pharmaceutical Sciences)
  • Kamaljit Kaur (Faculty of Pharmacy and Pharmaceutical Sciences)
    Glen B. Baker (Department of Psychiatry)