Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and indomethacin are the most widely prescribed drugs to treat pain fever and inflammation. However, NSAIDs are associated with serious side effects, such as gastrotoxicity due to inhibition of cyclooxygenase-2 (responsible for pain and inflammation) as well as cyclooxygenase-1(responsible for protecting the gastric mucosa).Nitric oxide (NO) is an endogenous signaling molecule that is involved in various physiological functions, such as inhibition of platelet aggregation, protection of the stomach lining and immune regulation. To overcome the side effects of NSAIDs, NO based NSAIDs have been synthesized using different NO donors and have been shown to retain the anti-inflammatory and antipyretic activity of NSAIDs with reduced gastrointestinal toxicity. Nitroxyl (HNO) has also emerged as a biologically relevant nitrogen oxide, with promising results in treatment of cardiovascular diseases. We have recently shown the chemotherapeutic potential of HNO releasing asprin adducts. In an effort to establish these class of drug candidate as an alternative to conventional NSAIDs, we have synthesized NO/HNO releasing adducts of other NSAIDs.  Their NO/HNO release profile as well as their efficacy as cancer drug was examined.

Chemical and biological properties of nitrogen oxide releasing NSAIDs

243rd National Meeting (2012)

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