Update on COX-2 Selective Inhibitors: Chemical Classification, Side Effects and their Use in Cancers and Neuronal Diseases

Abstract

Inflammation is a complex phenomenon necessary in human defense mechanisms but also involved in the development of some human diseases. The discovery of cyclooxygenase-2 (COX- 2) improved the pharmacology of nonsteroidal anti-inflammatory drugs (NSAID) giving a clear mechanism for prostaglandin regulation in vivo and providing a new target for the development of COX-2-selective drugs without gastrointestinal side-effects. Keeping in view the importance of this pharmacological class, several literature reports have underlined the impact of these antiinflammatory compounds in therapeutics. The present review considers the most recently published literature concerning COX-2 inhibitors until 2016. Through a wide chemical classification, the last developments concerning this therapeutic family by highlighting structure-activity relationships insights and mechanisms are presented. A summary of the principal adverse effects observed and an overview of the new potential therapeutic indications for COX-2 inhibitors are also reported.

Study of the Inhibitory Effects of Enteral Nutrition Formula on Indomethacin-Induced Gastric Lesions in Mice

“…These drugs, however, also cause NSAID-induced ulcers by inhibiting the gastric mucosal protective effects of PG [1,2], characteristically producing relatively shallow ulcers predominantly in the pyloric antrum [3]. Since recent studies show that NSAID-induced ulcer is caused by the simultaneous inhibition of both COX-1 and COX-2, efforts have been continued to develop new COX inhibitors with selectivity for either COX-1 or COX-2 [4,5]. Although such selective inhibitors are less likely to cause the undesirable gastrointestinal side effects, most of the currently available NSAIDs exhibit gastrointestinal mucosal damage as a common adverse reaction.…”

In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates

“…Expression of COX-2 proteins and mRNA in human subjects show that COX-2 levels in normal tissues are the highest in the kidney followed by brain, then the spleen, liver, heart, and intestine [ 6 , 7 , 8 ]. COX-2 expression is upregulated in the inflammatory process in conditions, such as cancers, arthritis, autoimmune disorders, ischemic heart disease, stroke, organ rejection, and neurodegenerative diseases, like Alzheimer’s and Parkinson’s diseases [ 9 , 10 , 11 , 12 , 13 ]. Due to the involvement of COX-2 in diseases or disease processes, quantifying COX-2 expression is a potential biological marker for early diagnosis and for monitoring disease progression.…”

Radiosynthesis of a Novel 11C‐Labeled Derivative of 4’‐O‐Methylhonokiol and Its Preliminary Evaluation in an LPS Rat Model of Neuroinflammation

“…(In contrast, COX‐1 is constitutively expressed, but not induced by inflammation). This fact, combined with the large number of developed COX‐2‐selective inhibitors (COXIBs) makes this enzyme an attractive target for PET investigation of neuroinflammation. During the past few years, more than fifty compounds labeled with 11 C and 18 F have been proposed for imaging of COX‐2 expression .…”