Novel paeonol derivatives: Design, synthesis and anti-inflammatory activity in vitro and in vivo.
Bioorg Chem
; 98: 103735, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32171986
Paeonol has been proved to have potential anti-inflammatory activity, but its clinical application is not extensive due to the poor anti-inflammatory activity (14.74% inhibitory activity at 20 µM). In order to discover novel lead compound with high anti-inflammatory activity, series of paeonol derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. Structure-activity relationships (SARs) have been fully concluded, and finally (E)-N-(4-(2-acetyl-5-methoxyphenoxy)phenyl)-3-(3,4,5-trimet-hoxyphenyl)acrylamide (compound 11a) was found to be the best active compound with low toxicity, which showed 96.32% inhibitory activity at 20 µM and IC50 value of 6.96 µM against LPS-induced over expression of nitric oxide (NO) in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4, resulting in inhibiting of NF-κB and MAPK pathways. Further studies have shown that compound 11a has obvious therapeutic effect against the adjuvant-induced rat arthritis model.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Acetofenonas
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Artritis Experimental
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Diseño de Fármacos
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Antiinflamatorios no Esteroideos
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FN-kappa B
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Óxido Nítrico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Año:
2020
Tipo del documento:
Article