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aDepartment of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan bDepartment of Molecular and Cellular Parasitology, Juntendo University, School of Medicine, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan cGunma Prefectural College of Health Sciences, Maebashi, Gunma 371, Japan dResearch Laboratory of Minophagen Pharmaceutical Co. Zama-shi, Kanagawa 228, Japan eShibata Laboratory of Natural Medicinal Materials, Minophagen Pharmaceutical Co. Yotsuya, Shinjyuku-ku, Tokyo 160, Japan
Address for correspondence: Kiyoshi Kita, Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Voice: +81-3-5841-3526; fax: +81-3-5841-3444. kitak{at}m.u-tokyo.ac.jp
Parasites have exploited unique energy metabolic pathways as adaptations to the natural host habitat. In fact, the respiratory systems of parasites typically show greater diversity in electron transfer pathways than do those of host animals. These unique aspects of parasite mitochondria and related enzymes may represent promising targets for chemotherapy. Natural products have been recognized as a source of the candidates of the specific inhibitors for such parasite respiratory chains. Chalcones was recently evaluated for its antimalarial activity in vitro and in vivo. However, its target is still unclear in malaria parasites. In this study, we investigated that licochalcone A inhibited the bc1 complex (ubiquinol-cytochrome c reductase) as well as complex II (succinate ubiquinone reductase, SQR) of Plasmodium falciparum mitochondria. In particular, licochalcone A inhibits bc1 complex activity at very low concentrations. Because the property of the P. falciparum bc1 complex is different from that of the mammalian host, chalcones would be a promising candidate for a new antimalarial drug.
Key Words: parasite • mitochondria • chemotherapy • plasmodium • succinate • ubiquinone • licochalcone
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