NSAIDs between past and present; a long journey towards an ideal COX-2 inhibitor lead

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most abundantly used classes among therapeutic agents in medicine. NSAIDs inhibit the enzyme cyclooxygenase (COX), which is responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, non-selective NSAIDs are considered as a double-edged weapon since inhibition of COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. The detection of COX-2 role in inflammation process launched a new era in its management. Several trials have been established to proceed towards selectivity of well-defined anti-inflammatory members. COX-2 selective inhibitors are evidently safer on the gastrointestinal tract than non-selective NSAIDs. Nevertheless, their unexpected cardiovascular risks cannot be ignored. This review article highlights the latest trials aimed at developing new compounds with promising selective COX-2 activity.