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Bioorg Med Chem Lett ; 36: 127780, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33422605

RESUMO

Based on our previous report that 3-morpholino-1-phenylpropan-1-one 2, one of the fluoxetine's simplified morpholino analogue, inhibited nitric oxide (NO) production, in this paper, various substituted benzene analogues with morpholine hydrochloride of 2 were synthesized and their inhibitory effects on NO production in lipopolysaccharide (LPS)-induced BV2 cells were tested. Among the synthesized compounds, 2-trifluoromethyl analogue 16n (IC50 = 8.6 µM) showed a significantly higher inhibitory activity than that of the parent compound 2a (IC50 > 50 µM) and suppressed NO production dose-dependently without cytotoxicity. Compound 16n also inhibited iNOS expression in LPS-induced BV2 cells at 2, 10 and 20 µM concentrations. These results suggest that compound 16n inhibited NO production by suppressing the expression of iNOS and can be used as a lead structure for developing new inhibitor of NO production.


Assuntos
Cloretos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Morfolinas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Animais , Linhagem Celular , Cloretos/síntese química , Cloretos/química , Relação Dose-Resposta a Droga , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Morfolinas/síntese química , Morfolinas/química , Óxido Nítrico/biossíntese , Relação Estrutura-Atividade
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