Effect of nitroquine (Ci-679) in vitro on incorporation of [3H]hypoxanthine into DNA and RNA of Plasmodium yoelii

The effect of nitroquine acetate, together with pyrimethamine, was studied with [3H]hypoxanthine incorporation into DNA and RNA of Plasmodium yoelii during incubation in Men Eagle medium containing neither PABA nor folic acid. Incorporation into RNA was only slightly affected by nitroquine 10 vmol/L, whereas incorporation into DNA was markedly inhibited by nitroquine 0.1 nmol/L and pyrimethamine I nmol/L. When both drugs were at 10 vmol/L, inhibition of DNA synthesis was noted after 15 min of drug action. The inhibition was antagonized by PABA, folic and folinic acids when both antimalarials were at 10 nmol/L. In the absence of antimalarials, incorporation into DNA was stimulated by the 3 antagonists. The results indicate that nitroquine, like pyrimethamine, inhibits DNA synthesis of malaria parasites by interfering with their folic acid metabolism. which is one of the main antimalarial mechanisms of nitroquine.