Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies.
Bioorg Chem
; 78: 103-114, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29550530
ABSTRACT
A series of newly synthesized 4-aryl-hydrazonopyrazolones were designed and their structures were confirmed by spectral and elemental analyses. All synthesized compounds were evaluated for their in vitro COXs, 5-LOX inhibition, in vivo analgesic and anti-inflammatory activities. Compounds 5d, 5f and 5i were found to be the most potent COX-2/5-LOX inhibitors with superior COX-2 selectivity index values (SIâ¯=â¯5.29-5.69) to reference standard celecoxib (SIâ¯=â¯3.52). Four compounds; 5b, 5c, 5d and 5f showed excellent anti-inflammatory activity (% edema inhibitionâ¯=â¯72.72-54.54%) and perfect ED50 values (ED50â¯=â¯0.044-0.104â¯mmol/kg) relative to celecoxib (ED50â¯=â¯0.032â¯mmol/kg). To explore the most active compounds, ulcerogenic effect on stomach in comparison with indomethacin and celecoxib in addition to histopathological investigations were performed. Compound 5f showed better gastric profile (UIâ¯=â¯2.33) than celecoxib (UIâ¯=â¯3.00). Also, 5f caused 50% increase in thermal pain threshold close to reference drug indomethacin (53.13%). Docking study of all the target compounds into COX-2 and 5-LOX active sites was performed to rational their anti-inflammatory activities.
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfidrila
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Anti-Inflamatórios não Esteroides
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Inibidores de Lipoxigenase
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Pirazolonas
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Inibidores de Ciclo-Oxigenase 2
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Analgésicos
Limite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2018
Tipo de documento:
Article