کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6128418 1592802 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Novel inhibitors of the trypanosome alternative oxidase inhibit Trypanosoma brucei brucei growth and respiration
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی انگل شناسی
پیش نمایش صفحه اول مقاله
Novel inhibitors of the trypanosome alternative oxidase inhibit Trypanosoma brucei brucei growth and respiration
چکیده انگلیسی
African trypanosomiasis is a deadly disease for which few chemotherapeutic options are available. The causative agents, Trypanosoma brucei rhodesiense and T. b. gambiense, utilize a non-cytochrome, alternative oxidase (AOX) for their cellular respiration. The absence of this enzyme in mammalian cells makes it a logical target for therapeutic agents. We designed three novel compounds, ACB41, ACD15, and ACD16, and investigated their effects on trypanosome alternative oxidase (TAO) enzymatic activity, parasite respiration, and parasite growth in vitro. All three compounds contain a 2-hydroxybenzoic acid moiety, analogous to that present in SHAM, and a prenyl side chain similar to that found in ubiquinol. ACD15 and ACD16 are further differentiated by the presence of a solubility-enhancing carbohydrate moiety. Kinetic studies with purified TAO show that all three compounds competitively inhibit TAO, and two compounds, ACB41 and ACD15, have inhibition constants five- and three-fold more potent than SHAM, respectively. All three compounds inhibited the respiration and growth of continuously cultured T. b. brucei bloodstream cells in a dose-dependent manner. None of the compounds interfered with respiration of rat liver mitochondria, nor did they inhibit the growth of a continuously cultured mammalian cell line. Collectively, the results suggest we have identified a new class of compounds that are inhibitors of TAO, have trypanocidal properties in vitro, and warrant further investigation in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Acta Tropica - Volume 100, Issue 3, December 2006, Pages 172-184
نویسندگان
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