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.