Double prodrugs of a fosmidomycin surrogate as antimalarial and antitubercular agents.


Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 05 2019
Historique:
received: 17 12 2018
revised: 10 02 2019
accepted: 05 03 2019
pubmed: 19 3 2019
medline: 18 3 2020
entrez: 19 3 2019
Statut: ppublish

Résumé

A series of eleven double prodrug derivatives of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. A pivaloyloxymethyl (POM) phosphonate prodrug modification was combined with various prodrug derivatisations of the hydroxamate moiety. The majority of compounds showed activity comparable with or inferior to fosmidomycin against P. falciparum. N-benzyl substituted carbamate prodrug 6f was the most active antimalarial analog with an IC

Identifiants

pubmed: 30879839
pii: S0960-894X(19)30135-0
doi: 10.1016/j.bmcl.2019.03.009
pii:
doi:

Substances chimiques

Antimalarials 0
Antitubercular Agents 0
Carbamates 0
Nitrofurans 0
Prodrugs 0
Fosfomycin 2N81MY12TE
fosmidomycin 5829E3D9I9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1232-1235

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Charlotte Courtens (C)

Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.

Martijn Risseeuw (M)

Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.

Guy Caljon (G)

Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1 (S7), B-2610 Wilrijk, Belgium.

Louis Maes (L)

Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1 (S7), B-2610 Wilrijk, Belgium.

Paul Cos (P)

Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1 (S7), B-2610 Wilrijk, Belgium.

Anandi Martin (A)

Medical Microbiology, Institute of Experimental and Clinical Research, Université catholique de Louvain, Avenue Hippocrate 55, B-1200 Woluwe-Saint-Lambert, Belgium.

Serge Van Calenbergh (S)

Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: serge.vancalenbergh@ugent.be.

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Classifications MeSH