Abstract：
Species of Leishmania and Trypanosoma genera are the causative agents of relevant parasitic diseases. Survival inside their hosts requires the existence of a potent antioxidant enzymatic machinery. Four iron superoxide dismutases have been described in trypanosomatids (FeSODA, FeSODB1, FeSODB2, and FeSODC) that hold a potential as therapeutic targets. Nonetheless, very few studies have been developed that make use of the purified enzymes. Moreover, FeSODC remains uncharacterised in Leishmania. In this work, for the first time, we describe the purification and enzymatic activity of recombinant versions of the four Leishmania FeSOD isoforms and establish an improved strategy for developing inhibitors. We propose a novel parameter [(V*cyt. c - Vcyt. c)/Vcyt. c] which, in contrast to that used in the classical cytochrome c reduction assay, correlates linearly with enzyme concentration. As a proof of concept, we determine the IC50 values of two ruthenium carbosilane metallodendrimers against these isoforms.
摘要：
利什曼原虫和锥虫属是相关寄生虫病的病原体。在宿主内部生存需要存在有效的抗氧化酶机制。已经在锥虫中描述了四种铁超氧化物歧化酶（FeSODA，FeSODB1，FeSODB2和FeSODC）具有作为治疗靶标的潜力。尽管如此，很少有研究开发利用纯化的酶。此外，FeSODC在利什曼原虫中仍然没有特征。在这项工作中,第一次,我们描述了四种利什曼原虫FeSOD亚型的重组版本的纯化和酶活性，并建立了开发抑制剂的改进策略。我们提出了一个新的参数[(V*cyt。c-Vcyt。c)/Vcyt。c]其中，与经典的细胞色素C还原分析中使用的相反，与酶浓度呈线性关系。作为概念的证明，我们确定了两种钌碳硅烷金属树枝状聚合物对这些同工型的IC50值。
