Katarzyna Hoerchler
Northern Illinois
The methylerythritol 4-phosphate (MEP) pathway, is essential for the biosynthesis of isoprenoids in most bacteria, some eukaryotic parasites, and the plastids of plant cells. The development of inhibitors of this pathway may lead to novel classes of anti-infective agents or herbicides. The fourth enzyme of this pathway, IspE, catalyzes the phosphorylation of CDP-ME to CDP-ME2P. Recently, a series of 4-quinazolinones were reported to be inhibitors of IspE. However, it has been cited that the 4-quinazolinones may be inhibiting the auxiliary enzyme firefly luciferase rather than EcIspE, thus generating a false positive result. In order to clarify this issue, a series of 4-quinazolinones were synthesized in a three step sequence. In turn, these compounds were assayed against firefly luciferase to determine their inhibitory properties. Preliminary data is presented regarding the synthesis of 4-quinazolinone compounds along with subsequent inhibition assay results. Future work aims to utilize this class of inhibitors to assess structure-activity relationships within EcIspE.