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

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.

SUBMITTER: Hirsch DR 

PROVIDER: S-EPMC4798002 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature