Minagawa Nobuko
Department of Health Chemistry, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Akiha, Niigata, Japan.
Yakugaku Zasshi. 2012;132(10):1093-8. doi: 10.1248/yakushi.12-00220-1.
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.
生物为了在特定环境中生存,进化出了多种多样的能量代谢方式。线粒体电子传递系统存在显著差异,这可能是化疗的潜在靶点。阿托伐醌临床上用于治疗疟疾和肺孢子菌肺炎,是恶性疟原虫和耶氏肺孢子菌细胞色素bc(1)复合物中Qo位点的特异性抑制剂。植物病原真菌蚕豆壳二孢产生两种抗生素,即壳二孢素A和呋喃内酯。壳二孢素A特异性结合以抑制细胞色素bc(1)复合物中Qi和Qo位点的电子传递。除了独特的呼吸抑制作用外,目前正在进一步研究其对癌细胞的影响。另一方面,呋喃内酯特异性抑制对氰化物不敏感的锥虫替代氧化酶,该酶是布氏锥虫线粒体中的唯一末端氧化酶,可导致非洲锥虫病。体内研究表明,呋喃内酯有望成为治疗非洲锥虫病的化疗药物候选物。