卤代色氨酸衍生物破坏布氏锥虫血腔形式中的必需转氨机制。
Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei.
机构信息
Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Scotland.
Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
出版信息
PLoS Negl Trop Dis. 2020 Dec 4;14(12):e0008928. doi: 10.1371/journal.pntd.0008928. eCollection 2020 Dec.
Abstract
Amino acid metabolism within Trypanosoma brucei, the causative agent of human African trypanosomiasis, is critical for parasite survival and virulence. Of these metabolic processes, the transamination of aromatic amino acids is one of the most important. In this study, a series of halogenated tryptophan analogues were investigated for their anti-parasitic potency. Several of these analogues showed significant trypanocidal activity. Metabolomics analysis of compound-treated parasites revealed key differences occurring within aromatic amino acid metabolism, particularly within the widely reported and essential transamination processes of this parasite.
摘要
布氏锥虫（引起非洲人类锥虫病的病原体）内的氨基酸代谢对寄生虫的存活和毒力至关重要。在这些代谢过程中，芳香族氨基酸的转氨作用是最重要的之一。在这项研究中，研究了一系列卤代色氨酸类似物的抗寄生虫效力。其中几种类似物表现出显著的杀锥虫活性。对化合物处理的寄生虫进行代谢组学分析显示，芳香族氨基酸代谢中存在关键差异，特别是在该寄生虫广泛报道和必需的转氨过程中。
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