Inhibitors of the Bifunctional 2-C-Methyl-d-erythritol 4-Phosphate Cytidylyl Transferase/2-C-Methyl-d-erythritol-2,4-cyclopyrophosphate Synthase (IspDF) of Helicobacter pylori

A library of over 103 thousand compounds was screened for inhibitors of the IspD domain (2-C-methyl-d-erythritol 4-phosphate cytidylyl transferase domain) of the bifunctional IspDF protein from Helicobacter pylori using a photometric assay. Around 300 compounds showed IC50 values below 100m, and three compounds had IC50 values below 1 mu M. A few IspD inhibitors could also inhibit the IspF domain (2-C-Methyl-d-erythritol-2,4-cyclopyrophosphate synthase) of the IspDF protein. The most potent IspD inhibitors were tested as growth inhibitors of H. pylori. Several compounds showed inhibition of bacterial growth with IC50 in the single-digit m range. The most potent growth inhibitor had an IC50 value of 3.4 mu M. The most potent growth inhibitor without measurable effect on eukaryotic cell viability had an IC50 value of 7.2 mu M.