Alpha-heteroatom derivatized analogues of 3-(acetylhydroxyamino)propyl phosphonic acid (FR900098) as antimalarials
| Autor: | Jenny Pouyez, Louis Maes, Pierre Vandurm, Thomas Verbrugghen, Johan Wouters, Serge Van Calenbergh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Erythrocytes
Chemistry Pharmacology. Therapy Heteroatom Drug target Plasmodium falciparum Stereoisomerism In Vitro Techniques Fosmidomycin Molecular Docking Simulation chemistry.chemical_compound Antimalarials Structure-Activity Relationship 1-deoxy-D-xylulose 5-phosphate reductoisomerase Fosfomycin Parasitic Sensitivity Tests Drug Discovery parasitic diseases medicine Molecular Medicine Organic chemistry Humans Derivatization Aldose-Ketose Isomerases medicine.drug |
| Zdroj: | Journal of medicinal chemistry |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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