2. Academic Validation
  3. Acyloxybenzyl and Alkoxyalkyl Prodrugs of a Fosmidomycin Surrogate as Antimalarial and Antitubercular Agents

Acyloxybenzyl and Alkoxyalkyl Prodrugs of a Fosmidomycin Surrogate as Antimalarial and Antitubercular Agents

  • ACS Med Chem Lett. 2018 Sep 11;9(10):986-989. doi: 10.1021/acsmedchemlett.8b00223.
Charlotte Courtens 1,  Martijn Risseeuw 1,  Guy Caljon 2,  Paul Cos 2,  Serge Van Calenbergh 1
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.
PMID: 30344904 DOI: 10.1021/acsmedchemlett.8b00223
Abstract

Two classes of prodrugs of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. To this end, a novel efficient synthesis route was developed involving a cross metathesis reaction as a key step. Alkoxyalkyl prodrugs show decent antimalarial activities, but acyloxybenzyl prodrugs proved to be the most interesting and show enhanced antimalarial and antitubercular activity. The most active antimalarial analogues show low nanomolar IC50 values.

Figures