Structure-Activity Relationship Studies of a Series of Semisynthetic Lipopeptides Leading to the Discovery of Surotomycin, a Novel Cyclic Lipopeptide Being Developed for the Treatment of Clostridium difficile-Associated Diarrhea.
J Med Chem
; 58(12): 5137-42, 2015 Jun 25.
Article
en En
| MEDLINE
| ID: mdl-25993059
ABSTRACT
Novel cyclic lipopeptides with different acyl tails were synthesized via a semisynthetic approach. Structure-activity relationship studies revealed that lipophilicity, chain length, and the location of key aromatic functionalities of the tail modulated activity. The lead compound surotomycin exhibited significantly improved in vitro activity compared with daptomycin (MIC90 0.5 vs 2 µg/mL) against Clostridium difficile including NAP1 epidemic strains. In hamster efficacy studies, surotomycin protected animals at a dose of 0.5 mg/kg, PO.
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Plantas_medicinales
Asunto principal:
Enterocolitis Seudomembranosa
/
Clostridioides difficile
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Diarrea
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Lipopéptidos
/
Antibacterianos
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
J Med Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos