Trypanosome alternative oxidase as a target of chemotherapy
Trypanosome alternative oxidase as a target of chemotherapy
复制标题
DOI：
10.1016/s0925-4439(02)00086-8
复制
发表时间：
2002-07-18
影响因子：
6.2
通讯作者：
Kita, K
中科院分区：
文献类型：
--
作者：
Nihei, C;Fukai, Y;Kita, K
寄生虫已经发展出多种在宿主特殊环境中生存所必需的生理功能。它们利用与宿主非常不同的代谢系统，可以适应宿主动物体内存在的低氧张力。大多数寄生虫不利用宿主体内可用的氧气来产生 ATP，而是利用系统无氧代谢途径。这些寄生虫特异性途径中的酶是化疗的潜在靶标。对氰化物不敏感的锥虫替代氧化酶 (TAO) 是非洲锥虫细长血流形式呼吸链的末端氧化酶，可导致人类昏睡病和牛的纳加纳病。 TAO 已成为抗锥虫药物开发的目标，因为它不存在于宿主体内。最近，我们发现了迄今为止最有效的 TAO 抑制剂，壳二孢呋喃酮，这是一种从植物病原真菌 Ascochyta visiae 中分离出来的化合物。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Parasites have developed a variety of physiological functions necessary for their survival within the specialized environment of the host. Using metabolic systems that are very different from those of the host, they can adapt to low oxygen tension present within the host animals. Most parasites do not use the oxygen available within the host to generate ATP, but rather employ systems anaerobic metabolic pathways. The enzymes in these parasite-specific pathways are potential targets for chemotherapy. Cyanide-insensitive trypanosome alternative oxidase (TAO) is the terminal oxidase of the respiratory chain of long slender bloodstream forms of the African trypanosome, which causes sleeping sickness in human and nagana in cattle. TAO has been targeted for the development of anti-trypanosomal drugs because it does not exist in the host. Recently, we found the most potent inhibitor of TAO to date, ascofuranone, a compound isolated from the phytopathogenic fungus, Ascochyta visiae. (C) 2002 Elsevier Science B.V. All rights reserved.