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Alpha-O- or N-derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials

(2013) JOURNAL OF MEDICINAL CHEMISTRY. 56(1). p.376-380
Author
Organization
Abstract
To explore the hitherto successful derivatization of the alpha-carbon of fosmidomycin, a series of new a-substituted analogues was prepared. This was done by introduction of a heteroatom (N or O) in alpha-position to the phosphonate and using the resultant OH and NH2 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 alpha-azido-analogue and the alpha-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.
Keywords
AZIDES, INHIBITION, DRUG TARGET, FOSMIDOMYCIN-CLINDAMYCIN, 1-DEOXY-D-XYLULOSE-5-PHOSPHATE REDUCTOISOMERASE, DXR

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Chicago
Verbrugghen, Thomas, Pierre Vandurm, Jenny Pouyez, Louis Maes, Johan Wouters, and Serge Van Calenbergh. 2013. “Alpha-O- or N-derivatized Analogues of 3-(acetylhydroxyamino)propyl Phosphonic Acid (FR900098) as Antimalarials.” Journal of Medicinal Chemistry 56 (1): 376–380.
APA
Verbrugghen, Thomas, Vandurm, P., Pouyez, J., Maes, L., Wouters, J., & Van Calenbergh, S. (2013). Alpha-O- or N-derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials. JOURNAL OF MEDICINAL CHEMISTRY, 56(1), 376–380.
Vancouver
1.
Verbrugghen T, Vandurm P, Pouyez J, Maes L, Wouters J, Van Calenbergh S. Alpha-O- or N-derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials. JOURNAL OF MEDICINAL CHEMISTRY. 2013;56(1):376–80.
MLA
Verbrugghen, Thomas, Pierre Vandurm, Jenny Pouyez, et al. “Alpha-O- or N-derivatized Analogues of 3-(acetylhydroxyamino)propyl Phosphonic Acid (FR900098) as Antimalarials.” JOURNAL OF MEDICINAL CHEMISTRY 56.1 (2013): 376–380. Print.
@article{3230496,
  abstract     = {To explore the hitherto successful derivatization of the alpha-carbon of fosmidomycin, a series of new a-substituted analogues was prepared. This was done by introduction of a heteroatom (N or O) in alpha-position to the phosphonate and using the resultant OH and NH2 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 alpha-azido-analogue and the alpha-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       = {Verbrugghen, Thomas and Vandurm, Pierre and Pouyez, Jenny and Maes, Louis and Wouters, Johan and Van Calenbergh, Serge},
  issn         = {0022-2623},
  journal      = {JOURNAL OF MEDICINAL CHEMISTRY},
  language     = {eng},
  number       = {1},
  pages        = {376--380},
  title        = {Alpha-O- or N-derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials},
  url          = {http://dx.doi.org/10.1021/jm301577q},
  volume       = {56},
  year         = {2013},
}

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