Reverse fosmidomycin derivatives against the antimalarial drug target IspC (Dxr)

  • J Med Chem. 2011 Oct 13;54(19):6796-802. doi: 10.1021/jm200694q.
Christoph T Behrendt  1 ,  Andrea Kunfermann ,  Victoria Illarionova ,  An Matheeussen ,  Miriam K Pein ,  Tobias Gräwert ,  Johannes Kaiser ,  Adelbert Bacher ,  Wolfgang Eisenreich ,  Boris Illarionov ,  Markus Fischer ,  Louis Maes ,  Michael Groll ,  Thomas Kurz
Affiliations
  • 1. Institut für Pharmazeutische und Medizinische Chemie, Heinrich Heine Universität, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
PMID: 21866890 DOI: 10.1021/jm200694q
Abstract

Reverse hydroxamate-based inhibitors of IspC, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. The binding mode of one derivative in complex with EcIspC and a divalent metal ion was clarified by X-ray analysis. Pilot experiments have demonstrated in vivo potential.