含有phenoxypyridine的 chalcone衍生物的抗病毒活性评估和作用机制
Piao Mao1, Li Xing1, Bangcan He1
1National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals, Guizhou University, Guiyang, 550025, China.
Molecular diversity
|April 7, 2024
概括
新的氧二酸盐衍生物对烟草马赛克病毒 (TMV) 具有强大的抗病毒活性. 化合物L4表现出优异的治疗和保护作用,与TMV囊蛋白具有强烈的结合亲和力,表明它可能成为新型抗TMV药物.
科学领域:
- 药用化学 医学化学
- 植物病理学 植物病理学
- 有机合成 有机合成
背景情况:
- 烟草马赛克病毒 (TMV) 对农业生产力构成重大威胁.
- 现有的抗病毒药物往往具有局限性,需要开发新的治疗策略.
- 石衍生物以其多样化的生物活性,包括抗病毒性质而闻名.
研究的目的:
- 设计,合成和评估含有氧二的新型基衍生物作为潜在的抗TMV剂.
- 为了比较合成化合物的疗效与Ningnanmycin (NNM),一个已知的抗病毒控制.
- 调查最强效的衍生物对TMV的作用机制.
主要方法:
- 使用NMR和HRMS合成和表征28种含有氧二的基衍生物 (L1-L28).
- 对TMV进行抗病毒活性测试,包括治疗和保护作用,确定EC50值.
- 使用微尺度热泳 (MST) 和分子对接来评估与TMV囊蛋白 (TMV-CP) 的结合亲和力.
主要成果:
- 与NNM (148.3μg/mL) 相比,L1和L4化合物对TMV (EC50值140.5和90.7μg/mL) 具有更高的治疗活性.
- 与NNM (188.2μg/mL) 相比,L1,L4和L15显示出对TMV的增强保护活性 (EC50值为154.1,102.6和140.0μg/mL).
- L4对TMV-CP的结合亲和力明显高 (Kd = 0.00149 μM) 比NNM (Kd = 2.73016 μM),得到了分子对接的支持,表明结合更紧.
结论:
- 含有氧胺的基衍生物,特别是L4,具有作为针对TMV的新型抗病毒剂的显著潜力.
- L4的增强疗效归因于其强大的结合亲和力和与TMV-CP的相互作用.
- 对这些化合物的进一步研究和开发可能会导致有效的新药物用于TMV管理.
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