Trypanosome alternative oxidase as a target of chemotherapy

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.