L-Nucleoside Analogues as Potential Antimalarials That Selectively TargetPlasmodium FalclparumAdenosine Deaminase

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Abstract
The L-stereoisomer analogues of D-coformycin selectively inhibited P. falciparum adenosine deaminase (ADA) in the picomolar range (L-isocoformycin, K i 7 pM; L-coformycin, K i 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.