Alpha-heteroatom derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials

T. Verbrugghen, S. Van Calenbergh, Pierre Vandurm, Jenny Pouyez, Johan Wouters, L. Maes

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

To explore the hitherto successful derivatization of the α-carbon of fosmidomycin, a series of new α-substituted analogues was prepared. This was done by introduction of a heteroatom (N or O) in α-position to the phosphonate and using the resultant OH and NH groups as a handle for appending a variety of substituents by means of several functional groups such as ether, amide, urea, and 1,4-triazole. The synthesized molecules, as a racemic mixture, were assayed for their EcDXR inhibitory potency. Both the α-azido-analogue and the α-hydroxylated analogue proved most promising, and docking experiments were performed. Although several compounds showed high potency when assayed against Plasmodium falciparum K1 in human erythrocytes, a clear correlation between the enzyme inhibition constants and P. falciparum inhibition concentrations could not be found.
langue originaleAnglais
Pages (de - à)376-380
Nombre de pages5
journalJournal of Medicinal Chemistry
Volume56
Numéro de publication1
Les DOIs
étatPublié - 10 janv. 2013

Empreinte digitale

Antimalarials
Plasmodium falciparum
Organophosphonates
Triazoles
Amides
Ether
Urea
Carbon
Erythrocytes
Enzymes
3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid
fosmidomycin

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title = "Alpha-heteroatom derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials",
abstract = "To explore the hitherto successful derivatization of the α-carbon of fosmidomycin, a series of new α-substituted analogues was prepared. This was done by introduction of a heteroatom (N or O) in α-position to the phosphonate and using the resultant OH and NH groups as a handle for appending a variety of substituents by means of several functional groups such as ether, amide, urea, and 1,4-triazole. The synthesized molecules, as a racemic mixture, were assayed for their EcDXR inhibitory potency. Both the α-azido-analogue and the α-hydroxylated analogue proved most promising, and docking experiments were performed. Although several compounds showed high potency when assayed against Plasmodium falciparum K1 in human erythrocytes, a clear correlation between the enzyme inhibition constants and P. falciparum inhibition concentrations could not be found.",
author = "T. Verbrugghen and {Van Calenbergh}, S. and Pierre Vandurm and Jenny Pouyez and Johan Wouters and L. Maes",
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Alpha-heteroatom derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials. / Verbrugghen, T.; Van Calenbergh, S.; Vandurm, Pierre; Pouyez, Jenny; Wouters, Johan; Maes, L.

Dans: Journal of Medicinal Chemistry, Vol 56, Numéro 1, 10.01.2013, p. 376-380.

Résultats de recherche: Contribution à un journal/une revueArticle

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T1 - Alpha-heteroatom derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials

AU - Verbrugghen, T.

AU - Van Calenbergh, S.

AU - Vandurm, Pierre

AU - Pouyez, Jenny

AU - Wouters, Johan

AU - Maes, L.

N1 - Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2013/1/10

Y1 - 2013/1/10

N2 - To explore the hitherto successful derivatization of the α-carbon of fosmidomycin, a series of new α-substituted analogues was prepared. This was done by introduction of a heteroatom (N or O) in α-position to the phosphonate and using the resultant OH and NH groups as a handle for appending a variety of substituents by means of several functional groups such as ether, amide, urea, and 1,4-triazole. The synthesized molecules, as a racemic mixture, were assayed for their EcDXR inhibitory potency. Both the α-azido-analogue and the α-hydroxylated analogue proved most promising, and docking experiments were performed. Although several compounds showed high potency when assayed against Plasmodium falciparum K1 in human erythrocytes, a clear correlation between the enzyme inhibition constants and P. falciparum inhibition concentrations could not be found.

AB - To explore the hitherto successful derivatization of the α-carbon of fosmidomycin, a series of new α-substituted analogues was prepared. This was done by introduction of a heteroatom (N or O) in α-position to the phosphonate and using the resultant OH and NH groups as a handle for appending a variety of substituents by means of several functional groups such as ether, amide, urea, and 1,4-triazole. The synthesized molecules, as a racemic mixture, were assayed for their EcDXR inhibitory potency. Both the α-azido-analogue and the α-hydroxylated analogue proved most promising, and docking experiments were performed. Although several compounds showed high potency when assayed against Plasmodium falciparum K1 in human erythrocytes, a clear correlation between the enzyme inhibition constants and P. falciparum inhibition concentrations could not be found.

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