作为替代原发性阿梅比克脑膜炎治疗的替代药物,Nitroxoline的重新使用
Javier Chao-Pellicer1,2,3, Iñigo Arberas-Jiménez1,2, Frieder Fuchs4,5
1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Spain.
Antibiotics (Basel, Switzerland)
|August 26, 2023
概括
尼트로克索林对Naegleria fowleri表现出强烈的活性,这是原发性阿米巴脑膜炎 (PAM) 的原因. 这种药物重新利用为这种致命的寄生虫感染提供了一个有前途的新治疗策略.
科学领域:
- 传染性疾病 传染性疾病
- 寄生虫学的寄生虫学
- 药物发现 药物发现 药物发现
背景情况:
- 病原性自由活 (FLA),包括Naegleria fowleri,导致严重的中枢神经系统感染.
- 初级虫脑膜炎 (PAM) 是一种快速致命的疾病,死亡率高 (>97%).
- 目前对PAM的治疗选择有限,通常是无效的,需要寻找新的治疗药物.
研究的目的:
- 为了评估Nitroxoline对Naegleria fowleri的抗寄生虫活性.
- 为了评估Nitroxoline对N. fowleri. 的形和囊阶段的疗效.
- 确定Nitroxoline作为用于PAM治疗的重用药物的治疗潜力.
主要方法:
- 药物重新定位方法测试Nitroxoline的疗效.
- 在体外测试以确定针对N. fowleri和囊的IC50值.
- 评估Nitroxoline的活性与其在宿主细胞中的毒性相比.
主要成果:
- 尼特罗克索林对N. fowleri trophozoites (IC50值为1.63 ± 0.37 μM和1.17 ± 0.21 μM) 的微分子活性较低.
- 还观察到对N. fowleri囊阶段 (IC50为1.26±0.42μM) 的有效活性.
- 在以往对宿主细胞的研究中,尼트로克索林表现出有利的选择性指数 (3.78和5.25),表明其具有良好的安全性.
结论:
- 尼托克索林具有强大的抗寄生虫活性,可以对抗Naegleria fowleri.
- 这种药物诱导了N. fowleri.的编程细胞死亡 (PCD) 相关事件.
- 尼特洛克是开发一种替代性治疗原发性有菌性脑膜炎的有希望的候选药物.
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