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)
; 357(5): e2300615, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38315093
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 â¼80%. 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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Araquidonato 15-Lipooxigenasa
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Diseño de Fármacos
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Inhibidores de la Lipooxigenasa
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Especies Reactivas de Oxígeno
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Inhibidores de la Ciclooxigenasa 2
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Simulación del Acoplamiento Molecular
Límite:
Animals
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Humans
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Egipto