Nitric Oxide-NASIDS Donor Prodrugs as Hybrid Safe Anti-inflammatory Agents.

Selective inhibition of cyclooxygenase-2 (COX-2) isozyme afforded a useful drug design concept that resulted in the development of effective anti-inflammatory drugs that are devoid of adverse side effects, in particular gastrointestinal irritation, ulcerogenicity and renal toxicity attributed to inhibition of the cytoprotective cyclooxygenase-1 (COX-1) isozyme. Unfortunately, some selective COX-2 inhibitory drugs such as rofecoxib and valdecoxib are believed to be responsible for cardiovascular complications. Nitric oxide (NO) is an effective vasodilator that also inhibits platelet aggregation. Therefore hybrid NSAIDs containing NO-donor moieties have been developed to obtain effective treatment of inflammation with reduced GI and cardiovascular side effects. Here we review some of the most promising recent advances in NO-NAISDs donor drug development and summarizes medicinal chemistry efforts in search for new NO-NSAIDs prodrugs in an attempt to pave the way for further development in this promising area of research.