Discovery and structure-activity relationship analysis of Staphylococcus aureus sortase A inhibitors.
Bioorg Med Chem
; 17(20): 7174-85, 2009 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-19781950
ABSTRACT
Methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Using high-throughput screening, we have identified several compounds that inhibit the enzymatic activity of the SrtA. A structure-activity relationship (SAR) analysis led to the identification of several pyridazinone and pyrazolethione analogs that inhibit SrtA with IC(50) values in the sub-micromolar range. Many of these molecules also inhibit the sortase enzyme from Bacillus anthracis suggesting that they may be generalized sortase inhibitors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridazinas
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Staphylococcus aureus
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Proteínas de Bactérias
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Aminoaciltransferases
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Inibidores Enzimáticos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article