Discovery and in vivo evaluation of alcohol-containing benzothiazoles as potent dual-targeting bacterial DNA supercoiling inhibitors.
Bioorg Med Chem Lett
; 24(17): 4215-22, 2014 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-25086682
ABSTRACT
A series of dual-targeting, alcohol-containing benzothiazoles has been identified with superior antibacterial activity and drug-like properties. Early lead benzothiazoles containing carboxylic acid moieties showed efficacy in a well-established in vivo model, but inferior drug-like properties demanded modifications of functionality capable of demonstrating superior efficacy. Eliminating the acid group in favor of hydrophilic alcohol moieties at C(5), as well as incorporating solubilizing groups at the C(7) position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
DNA Bacteriano
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DNA Super-Helicoidal
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Haemophilus influenzae
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Benzotiazóis
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Antibacterianos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2014
Tipo de documento:
Article