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Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

机译:等温微量热法研究曼氏血吸虫药

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摘要

Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current “gold standard” to assess the in vitro antischistosomal properties of test drugs; however, it is labor-intensive, subjective, and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery. The in vitro effects of praziquantel, oxamniquine, artesunate, and mefloquine on metabolic activity and parasite motility of Schistosoma mansoni (newly transformed schistosomula [NTS] and 49-day-old adult worms) were studied using isothermal microcalorimetry (IMC). Results were compared to morphological readouts of viability. Results obtained for the four drugs tested with phenotypic evaluation by microscopy and IMC showed a good correlation, but IMC also identified drug effects that were not visible by microscopic evaluation, and IMC precisely determined the onset of action of the test drugs. Similar sensitivities on NTS and adult schistosomes were observed for praziquantel and mefloquine, while slight differences in the drug susceptibilities of the two developmental stages were noted with oxamniquine and artesunate. IMC is a useful tool for antischistosomal drug discovery that should be further validated. In addition, our data support the use of NTS in in vitro antischistosomal drug assays.
机译:由于吡喹酮实际上是唯一可用于治疗和控制血吸虫病发病率的药物,因此需要其他抗血吸虫病药物。手动显微镜读数是目前评估测试药物体外抗血吸虫病性质的“金标准”;然而,这是劳动密集型的,主观的且难以标准化的。因此,需要开发用于抗血吸虫病药物发现的新颖工具。使用等温微量热法(IMC)研究了吡喹酮,氧杂苯醌,青蒿琥酯和甲氟喹对曼氏血吸虫(新转化的血吸虫[NTS]和49日龄成虫)的代谢活性和寄生虫运动的体外作用。将结果与生存力的形态学读数进行比较。通过显微镜和IMC用表型评估测试的四种药物获得的结果显示出良好的相关性,但是IMC还确定了通过显微镜评估看不到的药物作用,并且IMC精确地确定了试验药物的作用发作。吡喹酮和甲氟喹对NTS和成人血吸虫的敏感性相似,而奥沙米喹和青蒿琥酯在两个发育阶段的药敏性方面略有差异。 IMC是抗血吸虫病药物发现的有用工具,应进一步验证。此外,我们的数据支持在体外抗血吸虫药物测定中使用NTS。

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