设计,合成,抗TMV活动和Seco-pregnane C21类固醇及其衍生物的结构-活动关系
Ying Yan1,2, Pan Tang1, Siyu He1
1State Key Laboratory of Functions and Applications of Medicinal Plants & College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R & D, Guizhou Medical University, Guiyang 550025, China.
Journal of agricultural and food chemistry
|September 19, 2024
概括
新的seco-pregnane C21类固醇衍生物对烟草马赛克病毒 (TMV) 具有强大的抗病毒活性. 关键的结构修改,特别是C-3和特定的双重债券,对于这种增强的活动至关重要,识别有前途的新TMV药物候选者.
科学领域:
- 自然产品化学 自然产品化学
- 病毒学 病毒学
- 药用化学 医学化学
背景情况:
- 秒孕C21类固醇具有针对烟草马赛克病毒 (TMV) 的固有抗病毒特性.
- 这些类固醇用于抗病毒应用的结构修改和随后的结构-活性关系 (SAR) 仍然在很大程度上未被探索.
研究的目的:
- 为了研究自然的后孕C21类固醇结构变化的对其抗TMV活性的影响.
- 为抗病毒评估设计和合成新型玻璃素C和A衍生物.
主要方法:
- 新型玻璃素C和A衍生物的化学合成.
- 生物测试以评估抗TMV活性.
- 逆转录-聚合酶链反应 (RT-PCR) 和西式涂抹来评估病毒基因和蛋白质表达.
- 用于结合能量分析的计算模拟.
主要成果:
- 大多数合成的衍生品对TMV有显著的抗病毒活性.
- 化合物5g,5j和5l与ningnanmycin相比表现出更高的活性,成为强大的抗病毒候选者.
- 观察到TMV外套蛋白 (TMV-CP) 基因转录和蛋白质表达的减少.
- 发现了NtHsp70-1和NtHsp70-061基因表达的下调.
- 化合物5l对TMV外衣蛋白具有强烈的结合亲和力,结合能量为-56.2 kcal/mol.
结论:
- 继孕C21类固醇的结构修改可以显著增强对TMV的抗病毒活性.
- 在C-3的替代和在C-5/C-6和C-13/C-18的双键的存在对于高抗TMV疗效至关重要.
- 像5g,5j和5l这样的新衍生品代表了开发新的TMV治疗方法的有希望的线索.
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