Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction
Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction
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DOI：
10.1016/j.jinorgbio.2017.07.023
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发表时间：
2017-10-01
影响因子：
3.9
通讯作者：
Yoneyama, Kelly A. G.
中科院分区：
文献类型：
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作者：
Costa, Monica S.;Goncalves, Yasmim G.;Yoneyama, Kelly A. G.
利什曼病是一种由利什曼原虫属原虫引起的寄生虫病。目前的治疗所呈现的许多并发症，包括高毒性、高成本和寄生虫抗性，使得开发新的治疗剂是必不可少的。本研究旨在评估新型钌（II）配合物cis-[Ru-II（eta（2）-O2 CR）（dPPm）（2）] PF 6的抗利什曼原虫潜力，其中dppm =双（二苯膦基）甲烷，R = 4-丁基苯甲酸酯（bbato）1，4-（甲硫基）苯甲酸酯（mtbato）2和3-羟基-4-甲氧基苯甲酸酯（hmxbato）3在前鞭毛体细胞毒性及其对寄生虫-宿主相互作用的影响。通过MTT法分析复合物对亚马逊利什曼原虫、巴西利什曼原虫、婴儿利什曼原虫前鞭毛体和小鼠巨噬细胞（RAW 264.7）的细胞毒性。通过在两种不同浓度的每种复合物存在下进行的体外感染性测定来评价复合物对寄生虫-宿主相互作用的影响：前鞭毛体IC 50值和对90% RAW 264.7巨噬细胞无毒的浓度。配合物1-3对所有测定的利什曼原虫物种表现出有效的细胞毒活性。IC 50值范围为7.52-12.59 μ M（复合物1）、0.70-3.28 μ M（复合物2）和0.52-1.75 μ M（复合物3）。所有复合物在两个测试浓度下均显著抑制感染性指数。感染性抑制范围为37 - 85%。有趣的是，由于复合物作用引起的感染性抑制在任一测试浓度下均无显著差异，除了复合物1对婴儿利什曼原虫（利什曼原虫）。感染性抑制是由于感染的巨噬细胞百分比和每个巨噬细胞的寄生虫数量减少所致。两者合计的结果表明，这些新的钌（II）配合物在体外显着的杀利什曼原虫活性。
Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment including high toxicity, high cost and parasite resistance make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis-[Ru-II(eta(2)-O2CR)(dPPm)(2)]PF6, with dppm = bis(diphenylphosphino) methane and R = 4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC50 values ranged from 7.52-12.59 mu M (complex 1); 0.70-3.28 mu M (complex 2) and 0.52-1.75 mu M (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes.