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

摘要

A library of over 103 thousand compounds was screened for inhibitors of the IspD domain (2-C-methyl-Derythritol 4-phosphate cytidylyl transferase domain) of the bifunctional IspDF protein from Helicobacter pylori using a photometric assay. Around 300 compounds showed IC_(50) values below 100 μM, and three compounds had IC_(50) values below 1 μM. 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 IC_(50) in the single-digit μM range. The most potent growth inhibitor had an IC_(50) value of 3.4 μM. The most potent growth inhibitor without measurable effect on eukaryotic cell viability had an IC_(50) value of 7.2 μM.