Title:Nitric Oxide-NASIDS Donor Prodrugs as Hybrid Safe Anti-inflammatory Agents
Volume: 17
Issue: 8
Author(s): Khaled R.A. Abdellatif, Eman K.A. Abdelall and Rania B. Bakr
Affiliation:
Keywords:
Anti-inflammatory agents, Prodrugs, Nitric oxide, NONOates, Cyclooxygenase inhibition.
Abstract: 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.