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

Molecules

René Chofor³  Martijn D.P. Risseeuw³  Jenny Pouyez⁴  Chinchu Johny¹  Johan Wouters⁴  Cynthia S. Dowd²  Robin D. Couch¹ 

[1] Department of Chemistry and Biochemistry, George Mason University, Manassas, VA 20110, USA; E-Mails:;Department of Chemistry, George Washington University, Washington, DC 20052, USA; E-Mail:;Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, Ghent B-9000, Belgium; E-Mails:;Department of Chemistry, University of Namur, UNamur, Rue de Bruxelles 61, Namur B-5000, Belgium; E-Mails:

关键词: fosmidomycin;    DOXP reductoisomerase;    non-mevalonate pathway;    isoprenoid biosynthesis;    coordination chemistry;   

DOI  :  10.3390/molecules19022571

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.