Structural optimization of natural product fusaric acid to discover novel T3SS inhibitors of Salmonella.
Biochem Biophys Res Commun
; 582: 72-76, 2021 12 10.
Article
em En
| MEDLINE
| ID: mdl-34695753
ABSTRACT
Type III secretion system (T3SS) plays a critical role in host cell invasion and pathogenesis of Salmonella. We recently identified the mycotoxin fusaric acid (FA) as a T3SS inhibitor of Salmonella. Herein, twenty-two diphenylsulfane derivatives were designed and synthesized using FA as a lead compound through scaffold hopping. Among them, SL-8 and SL-19 possessing strong anti-T3SS and anti-invasion activity were identified as T3SS inhibitors with improvement in potency as compared to FA. The inhibitory mechanisms on SPI-1 did not depend on the HilD-HilC-RtsA-HilA or PhoP-PhoQ pathway or the assembly of T3SS needle complex. Accordingly, we proposed that the inhibitory effects of SL-8 and SL-19 on SPI-1 probably influence the formation of SicA/InvF-effector complex or other related proteins.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Salmonella typhimurium
/
Proteínas de Bactérias
/
Fatores de Transcrição
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Ácido Fusárico
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Chaperonas Moleculares
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Proteínas de Ligação a DNA
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Sistemas de Secreção Tipo III
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China