化学诱变海洋真菌WGC-25C-6突变株中混源倍半萜生物碱的结构多样性与抗流感活性研究

Stachybotrys属真菌代谢产生的混源倍半萜生物碱是一类具有很好抗流感先导化合物开发潜力的功能小分子。课题基于前期从海洋真菌Stachybotrys chartarum WGC-25C-6中发现了结构新颖、具有全新抗流感作用机制的混源倍半萜生物碱的工作基础上，拟开展菌株WGC-25C-6的系统性化学诱变筛选，以获得能够代谢产生新颖混源倍半萜生物碱同系物的突变株，并从中制备结构新颖的生物碱同系物。系统性研究该类生物碱的抗流感活性构-效关系，深入阐明其抗流感作用机制，进而发现全新靶点的海洋微生物来源抗流感先导化合物。为海洋微生物新药研发提供化学和药理学依据；开拓海洋微生物制药新用途。

Merosesquiterpenoid-based alkaloids produced by the genus of Stachybotrys are potential bioactive functional molecules for finding new anti-influenza virus drug lead compounds. On the base of previous results of bioactive merosesquiterpenoid-based alkaloids with new anti-influenza mechanism from marine-derived fungus Stachybotrys chartarum WGC-25C-6, this project aims to enrich the chemical diversity of targeted alkaloids of strain WGC-25C-6 by means of chemical mutagenesis. New structural alkaloids will be isolated and identified from selected mutant strains for structure-activity relationship studies. Anti-influenza mechanism of bioactive compounds will be studied to uncover the regulation of signaling pathway, which are promising for the inhibiting of influenza virus, so as to discover new target anti-influenza lead compound. In addition, this work provides chemical and pharmacological evidences for finding new drugs from marine microorganisms and the pharmaceutical application of them.