2. Academic Validation
  3. Dual COX-2 and 15-LOX inhibition study of novel 4-arylidine-2-mercapto-1-phenyl-1H-imidazolidin-5(4H)-ones: Design, synthesis, docking, and anti-inflammatory activity

Dual COX-2 and 15-LOX inhibition study of novel 4-arylidine-2-mercapto-1-phenyl-1H-imidazolidin-5(4H)-ones: Design, synthesis, docking, and anti-inflammatory activity

  • Arch Pharm (Weinheim). 2024 Feb 5:e2300615. doi: 10.1002/ardp.202300615.
Nermine A Osman 1,  Mostafa K Soltan 2 3,  Samar Rezq 4 5 6 7 8,  Joseph Flaherty 5 6 7 8,  Damian G Romero 5 6 7 8,  Ahmed S Abdelkhalek 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
  • 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
  • 3 Oman College of Health Sciences, Muscat, Oman.
  • 4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
  • 5 Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
  • 6 Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
  • 7 Women's Health Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
  • 8 Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
PMID: 38315093 DOI: 10.1002/ardp.202300615
Abstract

Novel arylidene-5(4H)-imidazolone derivatives 4a-r were designed and evaluated as multidrug-directed ligands, that is, inflammatory, proinflammatory mediators, and Reactive Oxygen Species (ROS) inhibitors. All of the tested compounds showed cyclooxygenase (COX)-1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15-lipoxygenase (15-LOX). Compounds 4f, 4l, and 4p exhibited COX-2 selectivity comparable to that of celecoxib, while 4k was the most selective COX-2 Inhibitor. Interestingly, the screened results showed that compound 4k exhibited a superior inhibition effect against 15-LOX and was found to be the most selective COX-2 Inhibitor over celecoxib, whereas compound 4f showed promising COX-2 and 15-LOX inhibitory activities besides its inhibitory effect against ROS production and its lowering effect of both tumor necrosis factor-α and interleukin-6 levels by ∼80%. Moreover, compound 4f attenuated the lipopolysaccharide-mediated increase in NF-κB activation in RAW 264.7 macrophages. The preferred binding affinity of these molecules was confirmed by docking studies. We conclude that arylidene-5(4H)-imidazolone scaffolds provide promising hits for developing new synthons with anti-inflammatory and antioxidant activities.

Keywords

NF-κB; arylidene-5(4H)-imidazolone; dual COX-2/15-LOX inhibitors; molecular docking; synthesis.

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