title: Mitochondrial ubiquinol-cytochrome c reductase and cytochrome c oxidase: chemotherapeutic targets in malarial parasites.
abstract: In order to demonstrate that the mitochondrial electron transport system may be a target for antimalarial drug design in the human malarial parasite Plasmodium falciparum, ubiquinol-cytochrome c reductase and cytochrome c oxidase were purified from mitochondria of the parasite cultivated in vitro. It was found that the catalytic efficiency of the two enzymes from the malarial parasite were markedly lower than those from mouse liver mitochondria. The classical inhibitors affecting different quinone binding sites of the mammalian reductase, antimycin and myxothiazole, which had little antimalarial activities on P.falciparum growth in vitro, were found to exhibit little inhibitory effect against the parasite reductase. The malarial parasite reductase was more sensitive to inhibition by the antimalarial drug, 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone, than the mammalian enzyme, suggesting both the therapeutic potential of the target and the drug.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. fmedjkk@chulkn.chula.ac.th
authors.forename: J
authors.initials: J
authors.lastname: Krungkrai
authors.forename: S R
authors.initials: SR
authors.lastname: Krungkrai
authors.forename: N
authors.initials: N
authors.lastname: Suraveratum
authors.forename: P
authors.initials: P
authors.lastname: Prapunwattana
mesh_terms: D000818:Animals; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV