植物化学品:一种理论上的ADME/毒素分析
Emily N Wekesa1, Njogu M Kimani1, Sarah N Kituyi2,3
1Department of Physical Sciences, University of Embu, Kenya.
概括
来自Zanthoxylum物种的天然产品显示出作为药物候选人的希望. 在 silico ADMET 分析中,许多化合物具有良好的口服生物可用性和高肠道吸收,尽管注意到一些心脏和毒性问题.
科学领域:
- 自然产品 化学 化学
- 药用化学 医学化学
- 计算毒理学计算毒理学
背景情况:
- 自然产品 (NPs) 是新药发现的重要来源,但由于毒性和高消耗率,在开发中面临挑战.
- 加快药物开发和降低NP的成本需要在早期阶段在基中进行ADMET (吸收,分布,新陈代谢,分泌和毒性) 分析.
- 在传统医学中历史上使用的Zanthoxylum属,含有大量的二次代谢产物,具有潜在的治疗应用.
研究的目的:
- 通过计算来评估来自Zanthoxylum物种的二次代谢产物的ADMET特性.
- 在这种天然产品类别中确定有前途的药物开发候选者.
- 在药物发现管道的早期评估潜在的负担,如毒性和心脏影响.
主要方法:
- 收集了406种来自Zanthoxylum物种的二次代谢物的数据集.
- 在 silico ADMET 分析中,使用各种计算工具和模型进行了分析.
- 评估了关键药物相似性参数,包括利宾斯基五项规则,相似性和毒性终点 (hERG抑制,AMES毒性,肝毒性,皮肤敏感性).
主要成果:
- 81%的化合物遵守了利宾斯基的五项规则,这表明口服生物可用性良好.
- 药物相似性从66.2%到88.1%不等,其中9.2%被预测为类似于的.
- 虽然没有化合物抑制了hERG I,但33%的化合物抑制了hERG II. 在30%的患者中观察到AMES毒性抑制,在23.6%的患者中观察到肝毒性,在22.2%的患者中观察到皮肤敏感性.
- 大多数化合物的高肠道吸收 (81.8%) 预测是有利于口服药物配方.
结论:
- 来自Zanthoxylum物种的二次代谢产物具有有利于药物开发的物理化学特性,包括良好的口服生物可用性和高肠道吸收.
- 在 silico ADMET 分析中,确定了具有潜在药物潜在的特定化合物,同时还突出了关于心脏影响和毒性的进一步研究领域.
- 这项研究强调了计算ADMET分析在降低自然产品药物开发风险和指导未来研究工作方面的价值.
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