کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3418088 | 1225494 | 2010 | 5 صفحه PDF | دانلود رایگان |
Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or “sleeping sickness,” which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC50 value: 1 nM) to eliminate trypanosomes in human infective strain cultures.
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► TAO amino acid sequence was identical among T. brucei subspecies.
► Efficacy of TAO inhibitor extends to the human infective T. brucei subspecies.
► In vitro study using T. b. rhodesiense indicated that ascofuranone was effective to eliminate trypanosomes in human infective strain culture.
Journal: Parasitology International - Volume 59, Issue 4, December 2010, Pages 560–564