一个复杂性到多样性的战略,用于andrographolide衍生和发现潜在的抗病毒和抗癌支架
Qi Xing1,2, Jiayin Zhang1, Jie Yang1
1Translational Innovation Center, Shenzhen Bay Laboratory, Shenzhen 518132, China. zhuzd@szbl.ac.cn.
Organic & biomolecular chemistry
|October 28, 2025
概括
这项研究引入了一个复杂性-多样性策略,从andrographolide中创建新的候选药物. 新的富含的化合物显示出有希望的抗SARS-CoV-2和抗癌活性,扩大了药物发现的可能性.
科学领域:
- 自然产品化学 自然产品化学
- 药用化学 医学化学
- 有机合成 有机合成
背景情况:
- 自然产品是药物发现中的重要支架.
- 多样化复杂的自然产品框架是一项挑战.
- 安德罗格拉福利德是一种有前途的类基架.
研究的目的:
- 开发一个复杂性到多样性 (CtD) 策略,用于andrographolide衍生.
- 为了合成新的丰富复杂分子.
- 评估新衍生品的生物活性.
主要方法:
- 可见光诱导的andrographolide的亚齐里丁化.
- 亚齐里丁中间体的后续转化.
- 螺旋-胺达和氨基替代三环系统的合成.
主要成果:
- 合成了阿齐里丁功能化的格拉化衍生物.
- 获得了新的螺旋-胺达和三环架构.
- 一些衍生品表现出强大的抗SARS-CoV-2 (EC50 = 2.8 μM) 和抗鼻癌 (EC50 = 5.4 μM) 活性.
- 该CtD战略提供了快速进入新的化学空间的机会.
结论:
- 该CtD战略使得安德罗格拉福利德的有效多样化成为可能.
- 这种方法产生具有显著生物活性的药物样分子.
- 该方法扩大了可访问的化学空间,从类原料到药物发现.
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