Most pathogenic bacteria utilize the 2-C-methyl-D-erythritol 4-phosphate pathway (MEP Pathway) to biosynthesize the isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the two precursors of the biosynthesis of their isoprenoids (e.g. ubiquinone). As the MEP pathway is absent in human, all enzymes are potential targets to design new antimicrobials.1 The second enzyme of the MEP pathway is the DXR enzyme, which catalyzes the concomitant rearrangement and reduction of the deoxyxylulose 5-phosphate 1 (DXP) into MEP 2 using the NADPH as hydrogen donor and a divalent cation i.e. Mn2+ or Mg2+ . Fosmidomycin 3, a phosphonate antibiotic, is a potent inhibitor of DXR.2 Investigations are presently oriented towards the design of fosmidomycin analogues with improved pharmacological properties. 3<br/>This project is focused on the synthesis of prodrugs of DXR bisubstrate inhibitors, a single molecule 4 that simultaneously targets the substrate (DXP) and the cofactor NADPH binding sites. The potential of the synthesized prodrugs to inhibit E. coli and M. smegmatis will be evaluated.

Synthesis of prodrugs of DXR bisubstrate inhibitors

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.