Synthesis of 1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-2-morpholinoethane-1,2-dione analogues and their inhibitory activities with reduced cytotoxicity in lipopolysaccharide-induced BV2 cells.
Bioorg Med Chem Lett
; 79: 129061, 2023 01 01.
Article
em En
| MEDLINE
| ID: mdl-36371018
ABSTRACT
A series of rimonabant analogues, where the N-aminopiperidine moiety was replaced by various amines and an additional carbonyl group, were synthesized and their inhibition of nitric oxide (NO) production was evaluated in lipopolysaccharide (LPS)-induced BV2 microglial cells. Among the synthesized compounds, the morpholine analogue 7y (IC50â¯=â¯4.71⯱â¯0.11⯵M) showed significantly higher inhibitory activity than rimonabant (IC50â¯=â¯16.17⯱â¯0.56⯵M), and suppressed NO production dose-dependently without cytotoxicity. In addition, 7y inhibited the expression of iNOS, COX-2 and pro-inflammatory cytokines and attenuated LPS-induced activation of nuclear factor-kappa B (NF-κB) and ERK MAPK phosphorylation in BV2 cells. These results demonstrated that 7y exerted anti-inflammatory effects by ERK pathway in BV2 cells, which can be used for the prevention and treatment of neuroinflammatory diseases.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Lipopolissacarídeos
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Rimonabanto
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Anti-Inflamatórios
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article