2. Academic Validation
  3. Phosphonodiamidate prodrugs of N-alkoxy analogs of a fosmidomycin surrogate as antimalarial and antitubercular agents

Phosphonodiamidate prodrugs of N-alkoxy analogs of a fosmidomycin surrogate as antimalarial and antitubercular agents

  • Bioorg Med Chem Lett. 2019 May 1;29(9):1051-1053. doi: 10.1016/j.bmcl.2019.03.008.
Charlotte Courtens 1,  Martijn Risseeuw 1,  Guy Caljon 2,  Paul Cos 2,  Anandi Martin 3,  Serge Van Calenbergh 4
Affiliations

Affiliations

  • 1 Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
  • 2 Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1 (S7), B-2610 Wilrijk, Belgium.
  • 3 Medical Microbiology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Avenue Hippocrate 55, B-1200 Woluwe-Saint-Lambert, Belgium.
  • 4 Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: serge.vancalenbergh@ugent.be.
PMID: 30857749 DOI: 10.1016/j.bmcl.2019.03.008
Abstract

A series of N-alkoxy analogs of a l-leucine ethyl ester phosphonodiamidate prodrug of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. These compounds originate by merging a previously reported successful phosphonate derivatisation with favorable modifications of the hydroxamate moiety. None of the synthesized compounds showed enhanced activity against either P. falciparum or M. tuberculosis in comparison with the parent free hydroxamate analog.

Keywords

Fosmidomycin; Isoprenoid biosynthesis; Malaria; Non-mevalonate pathway; Prodrugs; Tuberculosis.

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