Tetracyclic indolines as a novel class of β-lactam-selective resistance-modifying agent for MRSA
| Autor: | Shane Walls, Wei Wang, Yugen Zhu, Austin Jolly, Xiang Wang, Jessica D. Podoll, Lakota Cleaver |
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| Rok vydání: | 2017 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
0301 basic medicine Indoles medicine.drug_class 030106 microbiology Antibiotics Pharmacology beta-Lactams medicine.disease_cause Article Microbiology Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Antibiotic resistance Clavulanic acid Drug Resistance Bacterial Drug Discovery medicine Animals Humans Structure–activity relationship Organic Chemistry Drug Synergism General Medicine Amoxicillin Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents Community-Acquired Infections 030104 developmental biology chemistry Tetracyclines Staphylococcus aureus Lactam medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 125:130-142 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2016.09.034 |
| Popis: | Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relationships of a novel class of RMAs, tetracyclic indolines. These selectively potentiate β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) without antibacterial or β-lactamase inhibitory activity on their own. The most potent analogue, 6a, showed strong potentiation of amoxicillin/clavulanic acid in a variety of hospital-acquired and community-acquired MRSA strains with low mammalian toxicity. These compounds may be further developed to extend the clinic life span of β-lactam antibiotics. |
| Databáze: | OpenAIRE |
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