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
| Autor: | Jared Silverman, Prudencio Herradura, Yong He, Judith N. Steenbergen, Andrew D. G. Van Praagh, Lawrence I. Mortin, Ning Yin, Michael F. Mesleh, Andre Lee Pearson, Jing Li, Diane Citron, Carmela T. M. Mascio, Dennis Keith, Chester Metcalf, Grace M. Thorne, Karen Howland |
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| Rok vydání: | 2015 |
| Předmět: |
Diarrhea
Male Hamster Surotomycin Microbial Sensitivity Tests Peptides Cyclic Microbiology chemistry.chemical_compound Lipopeptides Structure-Activity Relationship Cricetinae Drug Discovery medicine Structure–activity relationship Animals Enterocolitis Pseudomembranous Clostridioides difficile Clostridium difficile In vitro Anti-Bacterial Agents Biochemistry chemistry Lipophilicity Molecular Medicine Daptomycin Lead compound medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 58(12) |
| ISSN: | 1520-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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