期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 9, 期 11, 页码 4057-4063出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c0ob01133a
关键词
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资金
- Life Sciences Institute
- College of Pharmacy at the University of Michigan
- Department of Chemistry at the University of Tel Aviv
- United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel [2008017]
- Marie Curie Action [246673]
Amongst the many synthetic aminoglycoside analogues that were developed to regain the efficacy of this class of antibiotics against resistant bacterial strains, the 1-N-acylated analogues are the most clinically used. In this study we demonstrate that 6'-N-acylation of the clinically used compound tobramycin and 6'-N-acylation of paromomycin result in derivatives resistant to deactivation by 6'-aminoglycoside acetyltransferase (AAC(6')) which is widely found in aminoglycoside resistant bacteria. When tested against AAC(6')- or AAC(3)-expressing bacteria as well as pathogenic bacterial strains, some of the analogues demonstrated improved antibacterial activity compared to their parent antibiotics. Improvement of the biological performance of the N-acylated analogues was found to be highly dependent on the specific aminoglycoside and acyl group. Our study indicates that as for 1-N-acylation, 6'- and 6'-N-acylation of aminoglycosides offer an additional promising direction in the search for aminoglycosides capable of overcoming infections by resistant bacteria.
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