中文摘要
从植物徐长卿中发现的C21-甾体及其皂苷具有显著的抗烟草花叶病毒的活性, Northern Blot研究表明,该类化合物主抑制病毒亚基因组RNA的复制,而对病毒基因组RNA没有影响。进一步研究发现C21-甾体及其皂苷对其它脊椎动物正链单链RNA病毒如辛德比斯病毒(SINV)等多种病毒的IC50为1-2nM,选择指数SI值在8250-16500之间。化合物同样选择性地抑制病毒亚基因组RNA的复制,而不影响病毒的基因组RNA。该研究结果具有原创性。由于是首次发现可选择性抑制病毒亚基因组RNA的小分子,该类C21-甾体化合物的活性中心及活性基团是什么?成为十分关键的问题,本研究是根据该类甾体化合物的结构特点,拟设计、合成其简化类似物,并通过抗正链单链RNA病毒活性的研究,探讨其活性中心和基团,阐明其构效关系,对我们深入探讨其作用机制和作用靶点、合理设计新一代的抗病毒药物,具有十分重要的学术意义。
英文摘要
C21-steroidal saponins from cynanchum paniculatum root of Traditional Chinese medicine has significant resistance activity to tobacco Mosaic virus activity(TMV). Studies show that these compounds are mainly inhibition of genomic RNA virus replication, Further research found these constitutes are selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus(SINV), but not to other RNA or DNA viruses. The calculated IC50 value for these compounds are between 1-2 nM, selection index SI values are between 8250-16500. The research findings are original. Because it is first discovered small molecules that can selectively inhibit virus and RNA genome. But what is the active center and active group of C21-steroidal compounds? This Become a crucial problem. This project is based on the structure characteristics of this kind of steroid compounds, to simplify design and synthesize their analogues, and research their antiviral activity to alphavirus-like positive-strand RNA viruses, discusses the active centers and groups, and to clarify the structure-activity relationship. These work have important academic significance to find the therapeutic targets, the mechanism of action and the reasonable design of a new generation of antiviral drugs.
