海洋真菌Cochliobolus lunatus中环十酯肽化合物cyclopeptolide 1的发现及其抗真菌活性研究  

Discovery and antifungal study of cyclopeptolide 1 from marine-derived fungus Cochliobolus lunatus

作　　者：彭书海 卢余盛 姚光山 PENG Shu-hai;LU Yu-sheng;YAO Guang-shan(Department of Stomatology,Xiamen Medical College,Xiamen 361023,China;Institute of Oceanography,Minjiang University,Fuzhou 350108,China)

机构地区：[1]厦门医学院口腔医学系,福建厦门361023 [2]闽江学院海洋研究院,福建福州350108

出　　处：《中国海洋药物》2020年第3期21-25,共5页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(81703555)资助。

摘　　要：目的利用"1个菌株-多个化合物"(OSMAC)方法研究海洋来源真菌Cochliobolus lunatus的次生代谢产物及其抗真菌活性。方法利用氮源丰富的GPY培养基诱导海洋来源真菌Cochliobolus lunatus产生新的酯肽类化合物,采用正相硅胶柱层析、凝胶柱层析、半制备高效液相色谱(HPLC)等方法对化合物进行分离纯化,利用核磁共振波谱学(NMR)和X-Ray单晶衍射手段并参考文献对化合物进行结构表征,利用各种活性模型对其进行系统的生物学活性评价。结果从海洋来源真菌分离获得环十酯肽化合物cyclopeptolide 1,并报道其晶体结构,发现其具有抗真菌活性(MIC=16μg/mL),并与临床药物氟胞嘧啶在抗真菌实验中显示协同效应。结论cyclopeptolide 1在抗真菌药物研发领域有望成为重要的先导化合物。Objective To investigate the secondary metabolites and their bioactivities of marine-derived filamentous fungus Cochliobolus lunatus by using the OSMAC method.Methods Nitrogen-rich GPY media was used to stimulate the fungus to produce novel lipopeptides in Cochliobolus lunatus.Combing forward column chromatography,Sephadex gel column chromatography and semi-prepared HPLC were applied to isolate novel lipopeptides,and its structure was elucidated by using NMR and X-ray crystal diffraction and compared with previously reported data.The various bioactivities were evaluated by using corresponding models.Results The compound cyclopeptolide 1 was isolated and its monocrystalline was first reported.It showed potent antifungal activities with MIC value of 16μg/mL,and had synergistic activity with flucytosine.Conclusion Cyclopeptolide 1 was a promising compound for the development of antifungal drugs.

关 键 词：Cochliobolus lunatus 环酯肽 抗真菌活性 白色念球菌 

分 类 号：R914[医药卫生—药物化学]