Inhibition of the ANT(2)-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic α-hydroxytropolones

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Hirsch, Danielle R.^1,2  Cox, Georgina³  D'Erasmo, Michael P.^1,2  Shakya, Tushar³  Meck, Christine^1,2  Mohd, Noushad¹  Wright, Gerard D.³  Murelli, Ryan P.^1,2 

[1] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA

[2] CUNY, Grad Ctr, Dept Chem, New York, NY 10016 USA

[3] McMaster Univ, Dept Biochem & Biomed Sci, MG DeGroote Inst Infect Dis Res, Hamilton, ON L8N 4K1, Canada

关键词: alpha-Hydroxytropolones;    Aminoglycoside-2 ''-O-nucleotidyltransferase;    Bacterial Resistance;    Aminoglycosides;    Gentamicin;   

DOI  :  10.1016/j.bmcl.2014.09.037

来源: Elsevier

【 摘 要 】

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 alpha-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. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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