合成和生物评价水溶性β-环极德-二烯酸合物
Hua LiWen1, Yi Yanliang1, Elena V Tretyakova2
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Natural product research
|April 29, 2024
概括
新的β-cyclodextrin (β-CD) 结合物显示出作为抗病毒剂的前景. 脱乙酸合物6b对奥米克朗SARS-CoV-2变体表现出显著的活性,这表明它有可能作为冠状病毒进入抑制剂.
科学领域:
- 药用化学 医学化学
- 病毒学 病毒学
- 纳米技术 纳米技术
背景情况:
- 亚比类型的二烯酸和β-环氧化 (β-CDs) 已知其生物活性.
- 点击化学为合分子提供了一个多功能平台.
- 开发针对SARS-CoV-2的新型抗病毒药物仍然是全球卫生优先事项.
研究的目的:
- 通过使用阿比类型的迪特尔酸合成新型β-cyclopodextrin (β-CD) 结合物.
- 评估这些结合物的抗病毒活性,以对抗野生型和小微型SARS-CoV-2伪病毒.
- 评估对大肠杆菌的抗菌活性和细胞毒性.
主要方法:
- 通过点击化学合成化物功能化的β-CDs及其与三种阿比类型的迪特尔酸的结合.
- 使用SARS-CoV-2尖端伪病毒 (野生型和欧米克朗变种) 的抗病毒测试.
- 对大肠杆菌的抗菌分析和对BHK-21-hACE2细胞的细胞毒性评估.
主要成果:
- 所有合成的结合物对BHK-21-hACE2细胞没有显著的细胞毒性 (细胞活力在15μM时>80%).
- 与其他测试的合物相比,七价值β-CD-脱乙酸合物 (6b) 显示出对抗SARS-CoV-2变种的增强抗SARS-CoV-2活性.
- 没有观察到对大肠杆菌的显著抗菌活性.
结论:
- 用点击化学有效合成β-CDs的多价值二烯酸衍生物.
- β-CD-脱乙酸合物6b显示出作为对SARS-CoV-2的入口抑制剂的潜力,特别是对Omicron变异的潜力.
- 这些发现表明,开发针对冠状病毒的新抗病毒疗法是一个有希望的途径.
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