Molecular Pharmacology, Vol 5, 376-381, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

Nuclear Magnetic Resonance Studies of the Interaction of Chloroquine Diphosphate with Adenosine 5'-Phosphate and Other Nucleotides

¹ Laboratory of Molecular Biology, University of Alabama in Birmingham, The Medical Center, Birmingham, Alabama 35233

The interaction of the antimalarial drug chloroquine diphosphate, 7-chloro-4-(4-diethylamino-1-methylbutylamino)quinoline diphosphate, with nucleotides has been studied by means of nuclear magnetic resonance spectroscopy. Certain of the proton resonances of the drug and the nucleotides are shifted as a result of the interaction.

This study shows that ring interactions occur in mixtures of chloroquine diphosphate and purine nucleotides, but appear to be minimal in drug mixtures containing pyrimidine nucleotides. Adenosine 5'-triphosphate, in contrast to adenosine 5'-phosphate, causes shifts of the chloroquine side chain proton signals in addition to those of the ring, suggesting an electrostatic interaction due to the presence of the additional phosphate groups. Interactions are decreased sharply at elevated temperatures. The differences observed between the shifts in proton signals of chloroquine in chloroquine-nucleotide mixtures and those observed at high concentrations of the drug alone suggest that the major interactions are between drug and nucleotide.