Identification and initial optimization of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB).
Bioorg Med Chem Lett
; 28(4): 756-761, 2018 02 15.
Article
em En
| MEDLINE
| ID: mdl-29331267
ABSTRACT
The discovery, synthesis and preliminary structure-activity relationship (SAR) of a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB) is described. A high throughput screening (HTS) campaign resulted in the identification of moderately active screening hits 1-5 the most potent of which was compound 1 (IC50â¯=â¯0.77⯵M). In silico docking of an early analog offered suggestions for structural modification which resulted in the design and synthesis of highly potent analogs 13j(IC50â¯=â¯1â¯nM) and 13â¯l(IC50â¯=â¯7â¯nM) which were chosen as leads for further optimization.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Toxinas Bacterianas
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Clostridioides difficile
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Antibacterianos
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Nucleotidases
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article