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Title
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Alpha-heteroatom derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Journal of medicinal chemistry. - Washington, D.C., 1963, currens
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Publication
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Washington, D.C.
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2013
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ISSN
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0022-2623
[print]
1520-4804
[online]
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DOI
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10.1021/JM301577Q
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Volume/pages
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56
:1
(2013)
, p. 376-380
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ISI
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000313221600031
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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