L-nucleoside analogues as potential antimalarials that selectively target Plasmodium falciparum adenosine deaminase

The L-stereoisomer analogues of D-coformycin selectively inhibited P. falci parum 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-aden osine, 2,6-diamino-9-(L-ribofuranosyl)purine and 4-amino-1-(L-ribofuranosyl )pyrazolo [3,4-d]-pyrimidine were selectively deaminated by P. falciparum A DA, L-thioinosine and L-thioguanosine were not. This is the first example o f 'non-physiological' L-nucleosides that serve as either substrates or inhi bitors of malarial ADA and are not utilised by mammalian ADA.