Structure-guided design of antibacterials that allosterically inhibit DNA gyrase.
Bioorg Med Chem Lett
; 29(11): 1407-1412, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-30962087
ABSTRACT
A series of DNA gyrase inhibitors were designed based on the X-ray structure of a parent thiophene scaffold with the objective to improve biochemical and whole-cell antibacterial activity, while reducing cardiac ion channel activity. The binding mode and overall design hypothesis of one series was confirmed with a co-crystal structure with DNA gyrase. Although some analogs retained both biochemical activity and whole-cell antibacterial activity, we were unable to significantly improve the activity of the series and analogs retained activity against the cardiac ion channels, therefore we stopped optimization efforts.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
DNA Girase
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Acinetobacter baumannii
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Escherichia coli
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Inibidores da Topoisomerase II
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Antibacterianos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2019
Tipo de documento:
Article