Botero Adriana, Keatley Sarah, Peacock Christopher, Thompson R C Andrew
School of Veterinary and Life Sciences, Murdoch University, South Street, Murdoch, WA 6150, Australia.
School of Veterinary and Life Sciences, Murdoch University, South Street, Murdoch, WA 6150, Australia.
Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):34-41. doi: 10.1016/j.ijpddr.2016.12.004. Epub 2016 Dec 23.
Trypanosomes are blood protozoan parasites that are capable of producing illness in the vertebrate host. Within Australia, several native Trypanosoma species have been described infecting wildlife. However, only Trypanosoma copemani has been associated with pathological lesions in wildlife hosts and more recently has been associated with the drastic decline of the critically endangered woylie (Bettongia penicillata). The impact that some trypanosomes have on the health of the vertebrate host has led to the development of numerous drug compounds that could inhibit the growth or kill the parasite. This study investigated and compared the in vitro susceptibility of two strains of T. copemani (G1 and G2) and one strain of Trypanosoma cruzi (10R26) against drugs that are known to show trypanocidal activity (benznidazole, posaconazole, miltefosine and melarsoprol) and against four lead compounds, two fenarimols and two pyridine derivatives (EPL-BS1937, EPL-BS2391, EPL-BS0967, and EPL-BS1246), that have been developed primarily against T.cruzi. The in vitro cytotoxicity of all drugs against L6 rat myoblast cells was also assessed. Results showed that both strains of T. copemani were more susceptible to all drugs and lead compounds than T. cruzi, with all IC50 values in the low and sub-μM range for both species. Melarsoprol and miltefosine exhibited the highest drug activity against both T. copemani and T. cruzi, but they also showed the highest toxicity in L6 cells. Interestingly, both fenarimol and pyridine derivative compounds were more active against T. copemani and T. cruzi than the reference drugs benznidazole and posaconazole. T. copemani strains exhibited differences in susceptibility to all drugs demonstrating once again considerable differences in their biological behaviour.
锥虫是血液原生动物寄生虫，能够在脊椎动物宿主中引发疾病。在澳大利亚，已描述了几种感染野生动物的本地锥虫物种。然而，只有考氏锥虫与野生动物宿主的病理损伤有关，并且最近还与极度濒危的毛尾袋鼬（Bettongia penicillata）的急剧减少有关。一些锥虫对脊椎动物宿主健康的影响促使人们开发了许多能够抑制寄生虫生长或杀死寄生虫的药物化合物。本研究调查并比较了两株考氏锥虫（G1和G2）和一株克氏锥虫（10R26）对已知具有杀锥虫活性的药物（苯硝唑、泊沙康唑、米替福新和美拉胂醇）以及四种主要针对克氏锥虫开发的先导化合物（两种苯菌灵和两种吡啶衍生物，即EPL-BS1937、EPL-BS2391、EPL-BS0967和EPL-BS1246）的体外敏感性。还评估了所有药物对L6大鼠成肌细胞的体外细胞毒性。结果表明，两株考氏锥虫比克氏锥虫对所有药物和先导化合物更敏感，两种锥虫的所有半数抑制浓度（IC50）值均处于低 microM 和亚 microM 范围内。美拉胂醇和米替福新对考氏锥虫和克氏锥虫均表现出最高的药物活性，但它们在L6细胞中也表现出最高的毒性。有趣的是，苯菌灵和吡啶衍生物化合物对考氏锥虫和克氏锥虫的活性均高于参考药物苯硝唑和泊沙康唑。考氏锥虫菌株对所有药物的敏感性存在差异，再次表明它们的生物学行为存在显著差异。
