结构新颖的萘醌色素和单萜苯酚类化合物的发现及抗HCV活性评价

项目名称： 结构新颖的萘醌色素和单萜苯酚类化合物的发现及抗HCV活性评价

项目编号： No.21262021

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 李蓉涛

作者单位： 昆明理工大学

项目金额： 52万元

中文摘要： 丙型肝炎为一严重危害人类健康的传染病，感染着全球约1.7亿人口，约80%感染者可发展成慢性肝炎，甚至肝硬化和肝癌。目前临床主要应用干扰素和利巴韦林联合治疗丙型肝炎，但有接近 50％的患者对治疗不敏感或无反应，并伴有明显的副作用。 我们在前期研究中发现具有显著抗HCV活性的萘醌色素和单萜苯酚类化合物，项目组将在此基础上继续对新疆紫草和滇紫草的抗HCV活性部位进行研究，以发现结构新颖的单萜苯酚和萘醌色素类化合物。通过2a型嵌合病毒（J6/JFH1）感染Huh 7.5.1细胞的HCV体外细胞培养体系，对分离得到的化合物进行抗HCV活性筛选，分析两种活性化合物配伍的抗病毒作用。同时，对有明显抗HCV作用的化合物的作用靶点进行初步研究，探索其可能的作用机理，评价细胞毒性，为发现靶点明确、高效低毒的抗HCV活性化合物，为进一步开发新的天然来源的抗HCV药物奠定基础。

中文关键词： 滇紫草；新疆紫草；单萜苯酚和萘醌类化合物；抗HCV活性；活性成分

英文摘要： The hepatitis C virus (HCV) infects about 170 million people worldwide. Its chronic infection is the cause of liver cirrhosis and hepatocellular carcinoma, and approximately 80% of infected individuals become chronically infected. Combination therapy of interferon-α and ribavirin formulation is the recommended treatment for HCV-infection. This combination therapy is limited by its only partial efficacy, and provokes severe side-effects. As part of a search for anti-HCV agents of natural origin, a phytochemical and bioactive investigation of Arnebia euchroma was carried out, and naphthoquinones and monoterpene phenols were found to exhibit potent anti-HCV activity. In order to search for more bioactive natural products, we will initiate chemical and bioactive studies on naphthoquinones and monoterpene phenols from two Boraginaceae species (A. euchroma and Onosma paniculatum). Our future works will include: (1) The isolation and identification of novel naphthoquinones and monoterpene phenols from A. euchroma and O. paniculatum. (2) The evaluation of anti-HCV effects of these compounds on the basis of 2a chimeric strains (J6/JFH1), Huh 7.5.1 HCV cell culture system in vitro, with interferon and ribavirin as positive control. The toxicities of the compounds were assayed by a modified MTT method, the anti-HCV activi

英文关键词： Onosma paniculatum；Arnebia euchroma；naphthoquinones and monoterpene phenols；anti-HCV activity；Bioactive constituents