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首页> 外文期刊>EBioMedicine >Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis
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Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis

机译：非甾体类抗炎药的表型筛选确定了甲芬那酸是治疗血吸虫病的药物

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Background Treatment and control of schistosomiasis, one of the most insidious and serious parasitic diseases, depend almost entirely on a single drug, praziquantel. Since the funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, 73 nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in medical and veterinary fields were evaluated for their anti-schistosomal properties. Methods The efficacy of NSAIDs was first tested against adult Schistosoma mansoni ex vivo using phenotypic screening strategy, effective drugs were further tested in a murine model of schistosomiasis. The disease parameters measured were worm and egg burden, hepato- and splenomegaly. Findings From 73 NSAIDs, five (mefenamic acid, tolfenamic acid, meclofenamic acid, celecoxib, and diclofenac) were identified to effectively kill schistosomes. These results were further supported by scanning electron microscopy analysis. In addition, the octanol-water partition coefficient, both for neutral and ionized species, revealed to be a critical property for the ex vivo activity profile. Compounds were then tested in vivo using both patent and a prepatent S. mansoni infection in a mouse model. The most effective NSAID was mefenamic acid, which highly reduced worm burden, egg production, and hepato- and splenomegaly. Interpretation The treatment regimen used in this study is within the range for which mefenamic acid has been used in clinical practice, thus, it is demonstrated the capacity of mefenamic acid to act as a potent anti-schistosomal agent suitable for clinical repurposing in the treatment of schistosomiasis.
机译：背景血吸虫病是最隐患和最严重的寄生虫病之一，其治疗和控制几乎完全依赖于一种药物吡喹酮。由于用于开发与贫困有关的疾病的药物的资金非常有限，因此，改变药物用途是一项有前途的战略。在这项研究中，对73种非甾体类抗炎药（NSAID）的抗血吸虫病性质进行了评估，这些非甾体类抗炎药通常用于医学和兽医领域。方法首先采用表型筛选策略对NSAIDs对成人曼氏血吸虫的体外疗效进行测试，然后在血吸虫病小鼠模型中进一步测试有效药物。测得的疾病参数是蠕虫和卵的负担，肝肿大和脾肿大。从73种非甾体类抗炎药中发现，有五种（甲芬那酸，甲苯磺酸，甲氯芬那酸，塞来昔布和双氯芬酸）可以有效杀死血吸虫。扫描电子显微镜分析进一步支持了这些结果。另外，中性和离子化物种的辛醇-水分配系数都显示出是离体活性分布的关键特性。然后在小鼠模型中同时使用专利和曼氏沙门氏菌感染对其进行体内测试。最有效的非甾体抗炎药是甲芬那酸，它可大大降低蠕虫负担，产卵量以及肝和脾肿大。解释本研究中使用的治疗方案在临床实践中已使用甲芬那酸的范围内，因此，证明了甲芬那酸具有作为强效抗血吸虫病药物的能力，适用于临床上针对甲乙酰胺的治疗。血吸虫病。

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