MITOCHONDRIAL UBIQUINOL-CYTOCHROME-C REDUCTASE AND CYTOCHROME-C-OXIDASE - CHEMOTHERAPEUTIC TARGETS IN MALARIAL PARASITES

In order to demonstrate that the mitochondrial electron transport syst em may be a target for antimalarial drug design in the human malarial parasite Plasmodium falciparum, ubiquinol-cytochrome c reductase and c ytochrome c oxidase were purified from mitochondria of the parasite cu ltivated in vitro. It was found that the catalytic efficiency of the t wo enzymes from the malarial parasite were markedly lower than those f rom mouse liver mitochondria. The classical inhibitors affecting diffe rent quinone binding sites of the mammalian reductase, antimycin and m yxothiazole, which had little antimalarial activities on P. falciparum growth in vitro, were found to exhibit little inhibitory effect again st the parasite reductase. The malarial parasite reductase was more se nsitive to inhibition by the antimalarial drug, rophenyl)cyclohexyl]-3 -hydroxy-1,4-naphthoquinone, than the mammalian enzyme, suggesting bot h the therapeutic potential of the target and the drug.