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

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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.

authors

  • Hirsch, Danielle R
  • Cox, Georgina
  • D’Erasmo, Michael P
  • Shakya, Tushar
  • Meck, Christine
  • Mohd, Noushad
  • Wright, Gerard
  • Murelli, Ryan P

publication date

  • November 2014