title: [Mitochondria as targets of chemotherapy].
abstract: Living organisms have developed a wide variety of energy metabolism to survive within the specialized environments. There is a remarkable diversity in mitochondrial electron transport system, which might be potential targets for chemotherapy. Atovaquone, clinically used to treat malaria and pneumocystis pneumonia, is a specific inhibitor of Qo site in the cytochrome bc(1) complex of Plasmodium falciparum and Pneumocystis jirovecii. Phytopathogenic fungus, Ascochyta viciae produces two antibiotics, ascochlorin and ascofuranone. Ascochlorin specifically binds to inhibit the electron transport of both Qi and Qo sites in cytochrome bc(1) complex. Besides the unique respiratory inhibition, further investigation is in progress to elucidate the effects on cancer cells. On the other hand, ascofuranone specifically inhibits cyanide-insensitive trypanosome alternative oxidase, which is a sole terminal oxidase in the mitochondrion of Trypanosoma brucei, causative of African trypanosomiasis. In vivo study suggests that ascofuranone is a promising candidate for chemotherapeutic agents to treat African trypanosomiasis.
authors.affiliation: Department of Health Chemistry, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha, Niigata, Japan. minagawa@nupals.ac.jp
authors.forename: Nobuko
authors.initials: N
authors.lastname: Minagawa
mesh_terms: D000475:Alkenes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000962:Antimalarials / Q000494:pharmacology*; D053626:Atovaquone / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000475:Alkenes; D000890:Anti-Infective Agents; D000962:Antimalarials; D010636:Phenols; D012717:Sesquiterpenes; C006640:ascofuranone; C415745:ascochlorin; D053626:Atovaquone