Pintavedenoton suhteen kriittisimmät väyläosuudet liikenteen ja väylänpidon kannalta

<i>N</i>-Leucinyl benzenesulfonamides have been discovered as a novel class of potent inhibitors of <i>E. coli</i> leucyl-tRNA synthetase. The binding of inhibitors to the enzyme was measured by using isothermal titration calorimetry. This provided information on enthalpy and entropy contributions to binding, which, together with docking studies, were used for structure–activity relationship analysis. Enzymatic assays revealed that <i>N</i>-leucinyl benzenesulfonamides display remarkable selectivity for <i>E. coli</i> leucyl-tRNA synthetase compared to <i>S. aureus</i> and human orthologues. The simplest analogue of the series, <i>N</i>-leucinyl benzenesulfonamide (R = H), showed the highest affinity against <i>E. coli</i> leucyl-tRNA synthetase and also exhibited antibacterial activity against Gram-negative pathogens (the best MIC = 8 μg/mL, <i>E. coli</i> ATCC 25922), which renders it as a promising template for antibacterial drug discovery