Structure–Activity Relationship for the Picolinamide Antibacterials that Selectively Target Clostridioides difficile
| Autor: | Mayland Chang, Enrico Speri, Allen G. Oliver, Elena Lastochkin, Man Wang, Jed F. Fisher, Jeshina Janardhanan, Stefania De Benedetti, Yuanyuan Qian, Shahriar Mobashery, Cesar Masitas, Valerie A. Schroeder, William R. Wolter |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
biology
010405 organic chemistry business.industry medicine.drug_class Organic Chemistry Antibiotics Gut flora medicine.disease_cause biology.organism_classification medicine.disease 01 natural sciences Biochemistry 0104 chemical sciences Microbiology 010404 medicinal & biomolecular chemistry Staphylococcus aureus Drug Discovery Medicine Structure–activity relationship Gut dysbiosis business Pathogen Dysbiosis Clostridioides |
| Zdroj: | ACS Med Chem Lett |
| Popis: | [Image: see text] Clostridioides difficile is a leading health threat. This pathogen initiates intestinal infections during gut microbiota dysbiosis caused by oral administration of antibiotics. C. difficile is difficult to eradicate due to its ability to form spores, which are not susceptible to antibiotics. To address the urgent need for treating recurrent C. difficile infection, antibiotics that selectively target C. difficile over common gut microbiota are needed. We herein describe the class of picolinamide antibacterials which show potent and selective activity against C. difficile. The structure–activity relationship of 108 analogues of isonicotinamide 4, a compound that is equally active against methicillin-resistant Staphylococcus aureus and C. difficile, was investigated. Introduction of the picolinamide core as exemplified by analogue 87 resulted in exquisite potency and selectivity against C. difficile. The ability of the picolinamide class to selectively target C. difficile and to prevent gut dysbiosis holds promise for the treatment of recurrent C. difficile infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|