Non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to treat a variety of inflammatory conditions. Many of these conditions, such as cancer or arthritis, require long term use of the NSAIDs due to the chronic nature of the disease. However, the NSAIDs in current use have toxicities associated with their long-term use that hinder their use for these chronic conditions.
Researchers at the NCI, in collaboration with Wake Forest University, have developed novel hybrid compounds which combine a NSAID with a nitroxyl (HNO) releasing agent. These modified NSAIDs have significantly reduced toxicity compared to the conventionally used NSAIDs which may allow their administration for the extended periods needed for more chronic conditions without severe side effects. The adverse side effects (i.e. heart attack, thrombosis and severe gut toxicity) observed with conventional NSAIDs are well documented. In fact, some of these drugs (i.e. Vioxx) were withdrawn from the market as a result of these adverse events. The compounds of the invention may alleviate these problems due to their lower toxicity. The HNO releasing moiety contained in the invention may expand the medical utility of NSAIDs. HNO releasing agents possess anticancer activity as well as good antioxidant properties, which has potential benefit for a variety of human diseases, including acute and chronic inflammation.