合成α-羟基托酚酮对ANT(2")-Ia耐药酶的抑制作用及氨基糖苷类抗生素活性的恢复
Inhibition of the ANT(2")-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic α-hydroxytropolones.
作者信息
Hirsch Danielle R, Cox Georgina, D'Erasmo Michael P, Shakya Tushar, Meck Christine, Mohd Noushad, Wright Gerard D, Murelli Ryan P
机构信息
Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States; Department of Chemistry, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States.
M. G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8N 4K1, Canada.
出版信息
Bioorg Med Chem Lett. 2014 Nov 1;24(21):4943-7. doi: 10.1016/j.bmcl.2014.09.037. Epub 2014 Sep 19.
Abstract
Aminoglycoside-2"-O-nucleotidyltransferase ANT(2")-Ia is an aminoglycoside resistance enzyme prevalent among Gram-negative bacteria, and is one of the most common determinants of enzyme-dependant aminoglycoside-resistance. The following report outlines the use of our recently described oxidopyrylium cycloaddition/ring-opening strategy in the synthesis and profiling of a library of synthetic α-hydroxytropolones against ANT(2")-Ia. In addition, we show that two of these synthetic constructs are capable of rescuing gentamicin activity against ANT-(2")-Ia-expressing bacteria.
摘要
氨基糖苷2″-O-核苷酸转移酶ANT(2″)-Ia是一种在革兰氏阴性菌中普遍存在的氨基糖苷抗性酶，是酶依赖性氨基糖苷抗性最常见的决定因素之一。以下报告概述了我们最近描述的氧化吡啶鎓环加成/开环策略在合成针对ANT(2″)-Ia的合成α-羟基托酚酮文库及其分析中的应用。此外，我们表明这些合成构建体中的两种能够恢复庆大霉素对表达ANT-(2″)-Ia的细菌的活性。
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