Synthetic Fosmidomycin Analogues with Altered Chelating Moieties Do Not Inhibit 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum Growth In Vitro

René Chofor; Martijn D.P. Risseeuw; Jenny Pouyez; Chinchu Johny; Johan Wouters; Cynthia S. Dowd; Robin D. Couch; Serge Van Calenbergh

doi:10.3390/molecules19022571

Molecules (Feb 2014)

Synthetic Fosmidomycin Analogues with Altered Chelating Moieties Do Not Inhibit 1-Deoxy-D-xylulose 5-phosphate Reductoisomerase or Plasmodium falciparum Growth In Vitro

René Chofor,
Martijn D.P. Risseeuw,
Jenny Pouyez,
Chinchu Johny,
Johan Wouters,
Cynthia S. Dowd,
Robin D. Couch,
Serge Van Calenbergh

Affiliations

René Chofor: Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium
Martijn D.P. Risseeuw: Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium
Jenny Pouyez: Department of Chemistry, University of Namur, UNamur, Rue de Bruxelles 61, Namur B-5000, Belgium
Chinchu Johny: Department of Chemistry and Biochemistry, George Mason University, Manassas, VA 20110, USA
Johan Wouters: Department of Chemistry, University of Namur, UNamur, Rue de Bruxelles 61, Namur B-5000, Belgium
Cynthia S. Dowd: Department of Chemistry, George Washington University, Washington, DC 20052, USA
Robin D. Couch: Department of Chemistry and Biochemistry, George Mason University, Manassas, VA 20110, USA
Serge Van Calenbergh: Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium

DOI: https://doi.org/10.3390/molecules19022571
Journal volume & issue: Vol. 19, no. 2
pp. 2571 – 2587

Abstract

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Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or the Plasmodia. This study further underlines the importance of the hydroxamate functionality and illustrates that identifying effective alternative bidentate ligands for this target enzyme is challenging.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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