Design, synthesis and molecular docking of 1,4-benzodioxane thiazolidinedione piperazine derivatives as FabH inhibitors.
Bioorg Chem
; 88: 102958, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31054434
ABSTRACT
A series of novel 1,4-benzodioxane thiazolidinedione piperazine derivatives targeting FabH were designed and synthesized. The compounds exhibited better inhibitory activity against Gram-negative bacteria by computer-assisted screening, antibacterial activity test and E. coli FabH inhibitory activity test, wherein compound 6j exhibited the most significant inhibitory activity (MICâ¯=â¯1.80â¯µΜ for P. aeruginosa, MICâ¯=â¯1.56â¯µΜ for E. coli). Besides, compound 6j still showed the best E. coli FabH inhibitory activity (IC50â¯=â¯0.06⯵Μ). Moreover, the antibacterial activities of all compounds were strongly correlated with the inhibitory ability of FabH, with a correlation coefficient of 0.954. Computational docking studies also showed that compound 6j has interacting with FabH key residues in the active site.
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Base de dados:
MEDLINE
Assunto principal:
Acetiltransferases
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Proteínas de Escherichia coli
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Tiazolidinedionas
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Dioxinas
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Inibidores Enzimáticos
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Simulação de Acoplamento Molecular
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Piperazina
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article