Selective COX-2 inhibitors as anticancer agents: a patent review (2014-2018)

ABSTRACT

Introduction: COX-2 is a key enzyme in the process of prostaglandins (PGs) synthesis. The products of this enzyme could play a major role as the mediators of the inflammatory response and some other medical states such as cancer. The design and synthesis of novel selective COX-2 inhibitors have always been attractive to researchers. This review discusses the structures of novel COX-2 inhibitors synthesized during the last five years and describes their efficacy as anticancer agents.

Areas covered: It is well established that COX-2 is overexpressed in many different cancers and treatment with selective COX-2 inhibitors could relieve their symptoms and limit their adverse sequences.

Expert opinion: The diversity of selective COX-2 inhibitors is mainly related to the types of scaffolds. Monocyclic, bicyclic, tricyclic, and acyclic scaffolds with different pharmacological effects and toxicological profiles could be found in the family of selective COX-2 inhibitors. The great interest of the researchers in this field is due to the importance of selective COX-2 inhibitors as a relatively safe and effective set of compounds which could present different properties such as antirheumatic, anti-inflammatory, antiplatelet, anti-Alzheimer’s disease, anti-Parkinson’s disease, and anticancer.

KEYWORDS:

• Anticancer
• selective COX-2 inhibitors
• structure-activity relationship (SAR)
• synthesis

Article highlights

• COX-2 is a very important enzyme that plays many roles in the pathophysiology of many debilitating diseases such as chronic inflammation and cancer.

• COX-2 inhibitors could be good candidates for developing new anticancer agents; however, their toxicity must be considered carefully.

• In this study, the authors reviewed some novel selective COX-2 inhibitors and their COX-2 inhibition activity as well as their anticancer effects.

• The structure of selective COX-2 inhibitors is mainly based on a central core with two vicinal rings with a COX-2 pharmacophore group placed at para position of one ring. As the selectivity for COX-2 isoform and safety depend on the type of central core, the authors discussed the COX-2 inhibitors according to central scaffold.

• Many scaffolds including monocyclic, bicyclic, tricyclic, and linear cores with various anchoring groups such as primary sulfonamide and methylsulfonyl as well as non-classical cores such as organometallic structures and hybrid molecules were discussed in the review.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.