乌尔索酸酸和异-mukaadial酸与Plasmodium falciparum Hsp90结合,在体外废除了其监护人的功能
Andani A T Nndwammbi1, Tendamudzimu Harmfree Dongola2, Addmore Shonhai2
1Department of Biochemistry, Faculty of Science, University of Johannesburg, Johannesburg, 2006, South Africa.
Naunyn-Schmiedeberg's archives of pharmacology
|January 22, 2024
概括
新的抗疟疾化合物 - - 异口酸 (IMA) 和酸酸 (UAA) - - 通过抑制热冲击蛋白90 (PfHsp90) 来向致命的疟疾寄生虫Plasmodium falciparum. 这两种化合物在体外和在体内都显示出显著的结合和破坏PfHsp90功能.
科学领域:
- 疟疾学 疟疾学
- 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 生物化学
- 结构生物学 结构生物学
背景情况:
- 疟原虫 (Plasmodium falciparum) 的耐药性需要新的抗疟疾药物.
- 热冲击蛋白90 (PfHsp90) 是一个有效的抗疟疾点.
- 伊索-穆卡迪亚乙酸 (IMA) 和乌尔索酸乙酸 (UAA) 显示出先前的抗疟疾活性.
研究的目的:
- 调查IMA和UAA与pfHsp90.0.0的结合情况.
- 通过生物化学分析验证in silico预测.
- 确定由IMA和UAA抑制PfHsp90的机制.
主要方法:
- 分子对接和动力学模拟.
- 生物化学分析:紫外线,FTIR,SPR.
- 伴侣活动和ATPase测定.
- 在体外抑制蛋白质聚合.
主要成果:
- UAA和IMA与pfHsp90的N端域结合,UAA显示更稳定的结合.
- 干结合改变了PfHsp90的三级和二级结构.
- 在微分子范围 (SPR) 中,UAA与PfHsp90结合.
- 这两种化合物都抑制了PfHsp90的霍尔达和ATPase活动.
- 在和体外的结果是一致的.
结论:
- IMA和UAA是潜在的抗疟疾药物,针对PfHsp90.
- 该研究验证了PfHsp90作为这些化合物的标.
- 这些发现扩大了作用于PfHsp90.0.的抗等离子体化合物的库.
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