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.
Original language | English |
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Pages (from-to) | 376-380 |
Number of pages | 5 |
Journal | Journal of Medicinal Chemistry |
Volume | 56 |
Issue number | 1 |
DOIs | |
Publication status | Published - 10 Jan 2013 |
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Physical Chemistry and characterization(PC2)
Johan Wouters (Manager) & Carmela Aprile (Manager)
Technological Platform Physical Chemistry and characterizationFacility/equipment: Technological Platform