Exploring of novel oxazolones and imidazolones as anti-inflammatory and analgesic candidates with cyclooxygenase inhibitory action

Abstract

Aim: Over the last few decades, therapeutic needs have led to a search for safer COX-2 inhibitors with potential anti-inflammatory and analgesic activity. Materials & methods: A new series of oxazolone and imidazolone derivatives 3a–c and 4a–r were synthesized and evaluated as anti-inflammatory and analgesic agents. COX-1/COX-2 isozyme selectivity testing and molecular docking were performed. Results: All compounds showed good activities comparable to those of the reference, celecoxib. The most active compounds 3a, 4a, 4c, 4e and 4f showed promising gastric tolerability with an ulcer index lower than that of celecoxib. The molecular docking of p-methoxyphenyl derivative 4c showed alkyl interaction with the side pocket His75 of COX-2 and achieved the best anti-inflammatory activity, with a COX-2 selectivity index better than that of celecoxib.

Graphical abstract

Summary points

Chemistry

• Novel oxazolone and imidazolone derivatives were designed and synthesized.

Biological activity

• The new compounds showed good analgesic and anti-inflammatory activities.

• The most active compounds showed good COX-2 selectivity.

• Compound 4c was the best anti-inflammatory agent.

• The selected compounds showed gastric tolerability.

Molecular docking

• Molecular docking found that the scaffold of the tested derivatives showed very similar binding pattern with the main hydrophobic channel residues of both isoenzymes.

• The high activity of the derivative 4c was attributable to the additional alkyl interaction with the side pocket His75 of COX-2.

Keywords: :

• analgesic
• anti-inflammatory
• COX-2 inhibitors
• imidazolone
• oxazolone

Financial disclosure

The authors have no 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity 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.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.