云南傣药植物内生放线菌新物种活性次生代谢产物研究

Finding higher efficient and lower toxic new bioactive leading compounds is the premise for new drug research and development, actinomycetes are one of the most important producer for bioactive substance, new actinomycetes species living inside plant hosts owe new gene which different from ordinary species, and have the special pathways in their metabolites and unique bioactive material synthesis ability during the long time co-evolution with their hosts, so they have more probability to produce novel bioactive components. Meanwhile, the toxicity of their secondary metabolites already been screened through plant body, the active components in their metabolite be of lower toxicity. The project will aim at the secondary metabolites of four new actinomycetes species isolated from Yunnan Dai medicine plants, which biosynthesis gene, biological activity and the chemistry diversity of their secondary metabolites have already been investigated in the primary research course. Isolated and purification the fermentation components, elucidate and determine compounds structures, test bioactive of new compounds in vitro. This research will focus in finding novel and lower toxic bioactive leading compounds, contributing to new natural active material discovery in our country and provide the novel structures comes from the original natural products for further organic synthesis.

寻找高效低毒的活性新先导化合物是新药研发的前提，放线菌是生物活性物质的重要产生菌，生存于植物体内的放线菌新物种具有与普通物种不同的新基因，在长期与宿主共同进化的过程中具有特殊的代谢途径及独特的生物活性物质合成能力，产生新结构活性化合物的几率较大。同时，其产物的毒性相当于已经过了植物体的筛选，从中发现的活性物质具有低毒性。本项目拟对经过生物合成基因、代谢产物活性及化学多样性筛选的四株分离自云南傣药植物的内生放线菌新物种的次生代谢产物进行研究，分离纯化菌株发酵产物中成分；确定纯化合物的结构并对新结构化合物进行离体生物活性测定。旨在发现微生物源低毒活性新先导化合物，为我国新型天然活性物质的发现作出贡献并为后续具有独特结构的天然产物合成提供源头。

放线菌是生物活性天然产物的重要产生菌，植物内生放线菌在长期与其植物宿主共同进化的过程中，具有特殊的代谢途径及独特的活性次生代谢产物合成能力，是寻找活性先导新化合物的重要资源。.项目完成了四株分离自云南傣药植物的植物内生放线菌的活性次生代谢产物研究，运用现代色谱分离技术，从四株菌株发酵产物中共分离纯化出27个单体化合物；通过波谱及光谱数据确定了其中25个化合物的结构；发现了Diastaphenazine及Strepeptolide 2个新结构化合物并对它们进行了离体生物活性测定。其中新化合物Diastaphenazine对人胃癌细胞株BGC-823、人宫颈癌细胞株Hela有较好的抑制作用，IC50 （ugmL-1）值分别为14.9和28.8，该化合物对金黄葡萄球菌Staphylococcus aureus也有抑制作用，其MIC值为64 ugmL-1。此外，对已知化合物测定了文献尚未报道的生物活性。.通过项目实施，发现了微生物源活性新先导化合物，丰富了天然产物数据库的结构多样性并为后续新天然产物的化学合成及新药的研发提供了活性先导新化合物。