STUDIES CONCERNING MECHANISM OF ACTION OF ANTIMALARIAL DRUGS - INHIBITION OF INCORPORATION OF ADENOSINE-8-3H INTO NUCLEIC ACIDS OF PLASMODIUM BERGHEI

A new system for the detection of the effects of antimalarial drugs on nucleic acids in Plasmodium berghei has been developed. Biochemical evidence for the incorporation of adenosine-8-3H into DNA and RNA of the parasite is presented with some preliminary conditions of incorporation. Dose-response curves established with the new system generally show inhibitory responses between 10-6M to 10-4M for quinine, quinacrine, ethidium bromide and between 10-4M to 10-3M for chloroquine. Quinacrine, quinine, chloroquine and ethidium have been reported to intercalate into the DNA helix based on physical and chemical evidence. DNA and RNA polymerase from E. coli are inhibited by these intercalating drugs and dose-response curves of inhibition by these drugs of adenosine incorporation are strikingly similar to doseresponse curves from isolated polymerase enzymes. The substantiation of the relative ineffectiveness of chloroquine as an antimalarial in P. berghei infections reveals the importance of defining antimalarial action on the basis of whole blood antimalarial activity. © 1969.