Abstract
The L-stereoisomer analogues of D-coformycin selectively inhibited P. falciparum adenosine deaminase (ADA) in the picomolar range (L-isocoformycin, Ki 7 pM; L-coformycin, Ki 250 pM). While the L-nucleoside analogues, L-adenosine, 2,6-diamino-9-(L-ribofuranosyl)purine and 4-amino-1-(L-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine were selectively deaminated by P. falciparum ADA, L-thioinosine and L-thioguanosine were not. This is the first example of 'non-physiological' L-nucleosides that serve as either substrates or inhibitors of malarial ADA and are not utilised by mammalian ADA.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Deaminase Inhibitors*
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Animals
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Antimalarials / chemical synthesis
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Antimalarials / chemistry
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Antimalarials / pharmacology*
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Antimetabolites / chemical synthesis
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Antimetabolites / chemistry
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Antimetabolites / pharmacology*
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Cattle
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Coformycin / analogs & derivatives*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Erythrocytes / enzymology
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Erythrocytes / parasitology
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Humans
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Molecular Structure
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Nucleosides / chemical synthesis
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Nucleosides / chemistry
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Nucleosides / pharmacology*
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / enzymology*
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Protozoan Proteins / antagonists & inhibitors*
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Stereoisomerism
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Substrate Specificity
Substances
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Adenosine Deaminase Inhibitors
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Antimalarials
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Antimetabolites
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Enzyme Inhibitors
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Nucleosides
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Protozoan Proteins
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Coformycin