Neuroprotective effect of novel celecoxib derivatives against spinal cord injury via attenuation of COX-2, oxidative stress, apoptosisand inflammation.
Bioorg Chem
; 101: 104044, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32629287
ABSTRACT
A novel series of celecoxib derivatives were synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities for benefit in spinal cord injury (SCI). The title compounds were synthesized by conventional methods in good yields and subsequently tested for inhibitory activity against COX-1/COX-2. The most potent COX-2 inhibitor among the tested derivatives was further assayed for protective effect against experimental SCI of Sprague-Dawley rats. The designed compounds showed considerable inhibition of COX-2 as compared to COX-1 revealing compound 7m as most potent inhibitor of COX-2 isoenzyme (IC50 = 0.04 µM). The expression of mitochondrial apoptotic genes (Bcl-2 and Bax) together with COX-2 and iNOS was restored near to normal as evidenced by western blot analysis in SCI rats. Taken altogether, compound 7m was identified as most potent inhibitor of COX-2. It also showed protective action against SCI via attenuation of COX-2, oxidative stress and apoptosis and inflammation in Male Sprague-Dawley rats.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Traumatismos de la Médula Espinal
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Apoptosis
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Estrés Oxidativo
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Ciclooxigenasa 2
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Inhibidores de la Ciclooxigenasa 2
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Celecoxib
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Inflamación
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2020
Tipo del documento:
Article
País de afiliación:
China