Second-generation 4,5,6,7-tetrahydrobenzo[d]thiazoles as novel DNA gyrase inhibitors.
Future Med Chem
; 12(4): 277-297, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-32043377
ABSTRACT
Aim:
DNA gyrase and topoisomerase IV are essential bacterial enzymes, and in the fight against bacterial resistance, they are important targets for the development of novel antibacterial drugs.Results:
Building from our first generation of 4,5,6,7-tetrahydrobenzo[d]thiazole-based DNA gyrase inhibitors, we designed and prepared an optimized series of analogs that show improved inhibition of DNA gyrase and topoisomerase IV from Staphylococcus aureus and Escherichia coli, with IC50 values in the nanomolar range. Importantly, these inhibitors also show improved antibacterial activity against Gram-positive strains.Conclusion:
The most promising inhibitor, 29, is active against Enterococcus faecalis, Enterococcus faecium and S. aureus wild-type and resistant strains, with minimum inhibitory concentrations between 4 and 8 µg/ml, which represents good starting point for development of novel antibacterials.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Girase
/
Benzotiazóis
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Inibidores da Topoisomerase II
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Bactérias Gram-Positivas
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Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2020
Tipo de documento:
Article