比斯-6-阿米迪诺-佐醇衍生物,可以用单剂量治疗试验阶段1非洲三虫病
Livio Racané1, Lucija Ptiček1, Sanja Kostrun2
1Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovića 28a, 10000 Zagreb, Croatia.
Journal of medicinal chemistry
|September 18, 2023
概括
一种新型的西醇化合物 (9a) 显示出对非洲试和疟疾寄生虫的强大活性. 这种候选药物具有显著的治疗潜力,对寄生虫细胞比人类细胞具有很高的选择性.
科学领域:
- 药用化学 医学化学
- 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:
- 非洲试和疟疾仍然是全球重大卫生挑战.
- 持续需要新型治疗药物,其疗效和安全性有所提高.
研究的目的:
- 设计,合成和评估新的bis-benzothiazole衍生物作为潜在的抗寄生虫剂.
- 为了确定负责三酸活性的关键结构特征.
- 评估化合物的有效性和安全性,以防非洲试和疟疾.
主要方法:
- 对称 bis-6-amidino-benzothiazole衍生物的合成.
- 在体外评估对Trypanosoma brucei和Plasmodium falciparum的抗寄生虫活性.
- 在试索米亚症小鼠模型中的体内疗效研究.
- 对哺乳动物细胞的选择性和体外ADME特性的评估.
主要成果:
- 化合物9a在试验室中表现出对Trypanosoma brucei的亚纳米强度,对哺乳动物细胞的选择性>26,000倍.
- 未被替代的5-胺基组和循环基间隔剂对类的活性至关重要.
- 一次剂量20mg/kg治愈了第1阶段的小鼠. trypanosomiasis.
- 化合物9a对异性Plasmodium falciparum具有较低的纳米分子活性,并且在体外具有有利的ADME概况,尽管膜透性较低.
- 有证据表明,T. brucei的吸收是通过内细胞分裂,导致 lysosomal 隔离.
结论:
- 化合物9a表现出强大的,跨物种的抗寄生虫活性和显著的选择性.
- 它代表了一种有前途的化合物,用于开发针对非洲试和疟疾的新疗法.
- 进一步调查其作用机制和体内药理动力学是有必要的.
相关概念视频
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