In vitro anti-malarial activity of N6-modified purine analogs.

A library of N-6 -hydroxy-, methoxy-, or amino-adenosine analogs was prepared and screened for anti-malarial properties. We found three compounds that possess anti-plasmodial activity in the low micromolar range against the multi-drug resistant Plasmodiurn falciparum VS1 strain, namely N-6-hydroxy-9H-purin-6-amine (IC50 5.57 mu M), 2-amino-N-6-amino-adenosine (IC50 12.2 mu M), and 2-amino-N-6 -amino-N-6-methyladenasine (IC50 0.29 mu M). More importantly, the compounds were non-toxic, with 2-amino-N-6-amino-N-6-methyladenosine showing a selectivity index of 5008.