针对潜在的新疗法的Leishmania donovani的双重向药物
Kushal Bora1,2, Manash Sarma1, Shankar Prasad Kanaujia2
1School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India.
Scientific reports
|October 26, 2023
概括
这项研究确定了两个新型化合物,ZINC000008876351和ZINC000008876351,它们抑制了Leishmania donovani中的关键抗氧化酶,显示了新的莱什曼病治疗的潜力.
科学领域:
- 寄生虫学的寄生虫学
- 药物发现 药物发现 药物发现
- 生物化学 生化学
背景情况:
- 莱什曼尼亚·多诺瓦尼寄生虫通过抗氧化酶在宿主氧化压力下生存.
- 线粒体铁超氧化物脱酶A (FeSODA) 和试氨酸减少酶 (TR) 对于寄生虫的生存至关重要.
- 抑制这些酶提供了对抗莱什曼病的潜在策略.
研究的目的:
- 在Leishmania donovani中识别抑制FeSODA和TR的多目标配体.
- 探索基于结构的药物设计和虚拟查新型抗莱什曼病化合物.
主要方法:
- 利用ZINC15数据库对类似药物的分子进行虚拟选.
- 采用标准精度 (SP) 和超精度 (XP) 的对接方法.
- 使用分子力学与一般化Born和表面积溶解 (MM-GBSA) 和体外试验验证实有希望的化合物.
主要成果:
- 两个化合物,ZINC000008876351和ZINC000008876351,表现出强大的结合亲和力和与FeSODA和TR的结合.
- 在体外测试显示了对Leishmania donovani promastigotes显著的抑制作用.
- 对于ZINC000008876351的IC50值为24.82 ± 0.61μM,对于ZINC000008876351的IC50值为7.52 ± 0.17μM.
结论:
- 已识别的化合物ZINC000008876351和ZINC000008876351对Leishmania donovani.表现出强大的抑制活性.
- 这些化合物代表了治疗莱什曼病的有希望的治疗候选者.
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