Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 12, Issue 12, Pages 1898-1904Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.1c00455
Keywords
Vancomycin; Antibiotic resistance; Bacterial biofilm; Antibiotics; Disulfides
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Funding
- Swiss National Science Foundation (SNSF) [182043]
- Bundesstipendium
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Novel vancomycin derivatives containing thiol-and disulfide-containing moieties exhibit enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin-resistant microbes and Gram-negative bacteria. These derivatives also demonstrate improved antibiofilm formation activity against VanB-resistant Enterococcus compared to vancomycin, providing a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation.
Antibiotic-resistant and biofilm-associated infections constitute a rapidly growing issue. Use of the last-resort antibiotic vancomycin is under threat due to the increasing appearance of vancomycin-resistant bacteria as well as the formation of biofilms. Herein, we report a series of novel vancomycin derivatives carrying thiol-and disulfide-containing moieties. The new compounds exhibited enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin-resistant microbes and Gram-negative bacteria. More-over, all obtained derivatives demonstrated improved antibiofilm formation activity against VanB-resistant Enterococcus compared to vancomycin. This work establishes a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation and advances the knowledge on the structural optimization of antibiotics with sulfur-containing modifications.
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