Innate inflammation beyond a threshold is a significant
problem
involved in cardiovascular diseases, cancer, and many other chronic
conditions. Cyclooxygenase (COX) enzymes are key inflammatory
markers as they catalyze prostaglandins production and are crucial
for inflammation processes. While COX-I is constitutively expressed
and is generally involved in “housekeeping” roles, the
expression of the COX-II isoform is induced by the stimulation of
different inflammatory cytokines and also promotes the further generation
of pro-inflammatory cytokines and chemokines, which affect the prognosis
of various diseases. Hence, COX-II is considered an important therapeutic
target for drug development against inflammation-related illnesses.
Several selective COX-II inhibitors with safe gastric safety profiles
features that do not cause gastrointestinal complications associated
with classic anti-inflammatory drugs have been developed. Nevertheless,
there is mounting evidence of cardiovascular side effects from COX-II
inhibitors that resulted in the withdrawal of market-approved anti-COX-II
drugs. This necessitates the development of COX-II inhibitors that
not only exhibit inhibit potency but also are free of side effects.
Probing the scaffold diversity of known inhibitors is vital to achieving
this goal. A systematic review and discussion on the scaffold diversity
of COX inhibitors are still limited. To address this gap, herein we
present an overview of chemical structures and inhibitory activity
of different scaffolds of known COX-II inhibitors. The insights from
this article could be helpful in seeding the development of next-generation
COX-II inhibitors.