基于结构的虚拟查方法揭示了用于开发抗疟疾药物的天然多标化合物,以对抗抗药性
Biswajit Naik1, Nidhi Gupta1, Priya Godara1
1Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, India.
Journal of biomolecular structure & dynamics
|August 2, 2023
概括
研究人员对抗疟疾药物点的天然化合物进行了选,以对抗日益增长的抗药性. 确定了有前途的化合物,显示出新抗疟疾疗法的潜力,具有最小的交叉耐药性风险.
科学领域:
- 药用化学 医学化学
- 寄生虫学的寄生虫学
- 计算生物学 计算生物学
背景情况:
- 疟疾病例在2021年增加了近200万例,突出显示迫切需要新的治疗方法.
- 抗药性Plasmodium falciparum菌株正在降低当前抗疟疾药物的疗效.
- 识别针对多个验证药物点的新型化合物对于克服耐药性至关重要.
研究的目的:
- 确定能够抑制Plasmodium falciparum中多个验证的药物标的天然化合物.
- 探索针对耐药疟疾寄生虫的新型治疗途径.
- 评估天然产品在打击日益增长的抗疟疾药物耐药性的潜力.
主要方法:
- 从NPASS数据库中对自然化合物的选与十个验证的Plasmodium falciparum药物标进行了选.
- 利用基于结构的分子对接来预测结合亲和关系和相互作用.
- 执行分子动力学模拟,以确认顶级化合物-目标复合物的稳定性.
主要成果:
- 20种天然化合物被确定为最受欢迎的药物,每种药物针对3到5种经过验证的药物标.
- 分子动力学模拟证实了六个选定的复合物的稳定结合,包括NPC246162和NPC271270.
- 分析表明结构与已知的抗疟疾药物有差异,这表明交叉耐药性风险较低.
结论:
- 鉴定到的天然化合物显示出希望,作为开发新抗疟疾药物的起点.
- 这些化合物可能为克服Plasmodium falciparum现有的耐药性提供了一种新的策略.
- 需要进一步的生化和体外研究来验证这些热门化合物的治疗潜力.
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