Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany.
J Med Chem. 2024 Jan 11;67(1):289-321. doi: 10.1021/acs.jmedchem.3c01357. Epub 2023 Dec 21.
The synthesis of a library of halogenated rocaglate derivatives belonging to the flavagline class of natural products, of which silvestrol is the most prominent example, is reported. Their antiviral activity and cytotoxicity profile against a wide range of pathogenic viruses, including hepatitis E, Chikungunya, Rift Valley Fever virus and SARS-CoV-2, were determined. The incorporation of halogen substituents at positions 4', 6 and 8 was shown to have a significant effect on the antiviral activity of rocaglates, some of which even showed enhanced activity compared to CR-31-B and silvestrol.
本文报道了一系列卤代罗卡格莱衍生物的合成，这些化合物属于天然产物 flavagline 类，其中以 silvestrol 最为突出。测定了它们对多种致病病毒（包括戊型肝炎、基孔肯雅热、裂谷热病毒和 SARS-CoV-2）的抗病毒活性和细胞毒性谱。结果表明，在 4'、6 和 8 位引入卤素取代基对罗卡格莱的抗病毒活性有显著影响，其中一些化合物的活性甚至比 CR-31-B 和 silvestrol 更强。
