10.1021/ml300169x.s001
Ed T. Buurman
Ed T.
Buurman
Valerie A. Laganas
Valerie A.
Laganas
Ce Feng Liu
Ce Feng
Liu
John I. Manchester
John I.
Manchester
Antimicrobial Activity
of Adenine-Based Inhibitors
of NAD<sup>+</sup>-Dependent DNA Ligase
American Chemical Society
2012
compound permeance
NAD
pneumoniae
LigA inhibitors
MIC
antimicrobial potency
Antimicrobial Activity
enzyme inhibition
pathogen
DNA
influenzae
MOA
2012-08-09 00:00:00
Dataset
https://acs.figshare.com/articles/dataset/Antimicrobial_Activity_of_Adenine_Based_Inhibitors_of_NAD_sup_sup_Dependent_DNA_Ligase/2497723
The relationship between enzyme inhibition and antimicrobial
potency
of adenine-based NAD<sup>+</sup>-dependent DNA ligase (LigA) inhibitors
was investigated using a strain of the Gram-negative pathogen <i>Haemophilus influenzae</i> lacking its major AcrAB-TolC efflux
pump and the Gram-positive pathogen <i>Streptococcus pneumoniae</i>. To this end, biochemical inhibitors not mediating their antibacterial
mode of action (MOA) via LigA were removed from the analysis. In doing
so, a significant number of compounds were identified that acted via
inhibition of LigA in <i>S. pneumoniae</i> but not in <i>H. influenzae</i>, despite being inhibitors of both isozymes.
Deviations from the line correlating antimicrobial and biochemical
potencies of LigA inhibitors with the correct MOA were observed for
both species. These deviations, usually corresponding to higher MIC/IC<sub>50</sub> ratios, were attributed to varying compound permeance into
the cell.