有抗炎活性黄酮糖苷的合成、结构衍生和构效关系研究

Four new flavonoid glycosides, with significant anti-inflammatory activity and without cytotoxicity, have been isolated from guangxi specialty herb, nervilia fordii (Hance) Schltr,(4 invention has applied for patents, have been authorized). Two of them are oxygen flavonoid glycosides, two are carbon flavonoid glycosides. But its natural sources of difficulties and content is very low, in order to obtain a large number of samples for further study, it is necessary to synthesis. This topic proposed through the route chosen by the concise, high chemical total synthesis, at the same time, in view of the defects they fat water distribution coefficient is low, the methods of etherification, esterification synthesis of series of derivatives. Use of lipopolysaccharide induce mice macrophage RAW264.7 release NO cell model, anti-inflammatory activity were traced. The computer aided drug design software, Sybyl, was used to carry out the quantitative structure-activity relationship, molecular docking, virtual screening and optimization design research. This research work was not reported, the results of the study are expected to get with completely independent intellectual property rights of new drug candidates or lead compounds.

本课题组从广西特产药材青天葵中分离追踪到4个有显著抗炎活性且基本无细胞毒性的新黄酮糖苷化合物（已申请4项发明专利，均已获授权），其中2个是黄酮氧苷，2个是黄酮碳苷。但其天然来源困难且含量很低，为获得大量样品以便深入研究，急需开展其结构的全合成。本课题拟通过简洁、高选择的路线进行化学合成，同时，针对它们脂水分配系数偏低的缺陷，采用醚化、酯化等方法合成系列衍生物。利用脂多糖诱导小鼠巨噬细胞 RAW264.7 释放 NO 的细胞模型，追踪化合物的抗炎活性并结合计算机辅助药物设计软件Sybyl开展定量构效关系、分子对接、虚拟筛选和优化设计研究。本研究工作国内外未见报道，研究结果有望获得具有完全自主知识产权的新药候选物或先导化合物。

本课题组前期从广西特产药材青天葵中分离追踪到4个有显著抗炎活性且基本无细胞毒性的新黄酮糖苷化合物（已申请4项发明专利，均已获授权）。但其天然来源困难且含量很低，为获得大量样品以便深入研究，本课题首先对黄酮类化合物进行了合成方法和药理作用的综述。通过简洁、高选择的路线进行化学合成，已合成36个黄酮类化合物，其中19个为未见报道的新化合物。利用脂多糖诱导小鼠巨噬细胞RAW264.7释放NO的细胞模型，追踪化合物的抗炎活性。还发现原定研究内容之外的情况：合成的黄酮化合物有一些具有较好的抗人三阴性乳腺癌细胞SUM149的活性。我们将结合计算机辅助药物设计软件Sybyl开展定量构效关系、分子对接、虚拟筛选和优化设计研究。本研究工作国内外未见报道，研究结果有望获得具有完全自主知识产权的新药候选物或先导化合物。目前已发表SCI论文1篇，申请发明专利2项，毕业硕士研究生1名。将要投稿论文2篇，申请发明专利1项。