In Vitro Anti-Malarial Activity Of N⁶-Modified Purine Analogs

Abstract

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 VS1 strain, namely N ⁶ -hydroxy-9H-purin-6-amine (IC ₅₀ 5.57 μ M), 2-amino-N ⁶ -amino-adenosine (IC ₅₀ 12.2 μ M), and 2-amino-N ⁶ -amino-N ⁶ -methyladenosine (IC ₅₀ 0.29 μ M). More importantly, the compounds were non-toxic, with 2-amino-N ⁶ -amino-N ⁶ -methyladenosine showing a selectivity index of 5008.

Keywords:

• Purines
• malaria
• nucleosides
• tautomers
• Plasmodium faciparum
• parasites

Acknowledgments

The authors would like to thank Dr. Harry de Koning at the University of Glasglow for helpful discussions regarding purine nucleobase/nucleoside transporters. They also wish to acknowledge the use of the EPSRC's Chemical Database Service at Daresbury. Finally, they are grateful to the Medical Research Council Technology (MRCT) Development GAP fund for financial support.