一株海绵共附生青霉Penicillium sp.的次级代谢产物研究  

Secondary metabolites of a marine sponge associated Penicillium sp.

作　　者：谢冬冬 李嘉欣 李培海 尚如意 刘可春 林厚文[1] 焦伟华[1] XIE Dongdong;LI Jiaxin;LI Peihai;SHANG Ruyi;LIU Kechun;LIN Houwen;JIAO Weihua(Research Center for Marine Drugs,State Key Laboratory of Oncogenes and Related Genes,Department of Pharmacy,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China;Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province,Biology Institute,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250103,China)

机构地区：[1]癌基因与相关基因国家重点实验室海洋药物研究中心,上海交通大学医学院附属仁济医院,上海200127 [2]山东省斑马鱼人类疾病模型与药物筛选工程技术研究中心,齐鲁工业大学(山东省科学院)生物研究所,山东济南250103

出　　处：《中草药》2024年第10期3223-3229,共7页Chinese Traditional and Herbal Drugs

基　　金：国家重点研发计划项目(2022YFC2804100);国家自然科学基金项目(82022068);国家自然科学基金项目(22137006)。

摘　　要：目的研究海绵共附生青霉Penicillium sp.LHW5975的化学成分。方法采用减压硅胶柱色谱、十八烷基硅烷键合硅胶填料(ODS)中压柱色谱和半制备高效液相色谱等技术进行分离纯化,得到的单体化合物通过高分辨-电喷雾-质谱(HRESI-MS)、核磁共振波谱(NMR)以及与文献比对等方法进行鉴定。对分离得到的化合物进行斑马鱼促血管生成活性评价。结果从Penicillium sp.LHW5975中分离纯化出9个生物碱类化合物,包括1个新的化合物,命名为青霉吲哚碱甲(1);以及8个已知化合物,分别为17-羟基短密青霉酰胺N(2)、苯并玛尔维碱A(3)、苯并玛尔维碱B(4)、苯并玛尔维碱C(5)、苯并玛尔维碱D(6)、苯并玛尔维碱E(7)、(−)-苯并玛尔维碱E(8)和N-甲基诺喔苯并玛尔维碱A(9)。化合物2和7在50µg/mL质量浓度下对斑马鱼节间血管的生长有促进作用。结论化合物1为新化合物,化合物2和9为青霉属内首分化合物,化合物2和7具有一定的促血管生成活性。Objective To reveal the secondary metabolites of the fermentation of marine sponge associated Penicillium sp.LHW5975.Methods The organic extract and fractions were separated and purified by silica vacuum liquid chromatography(VLC),octadecylsilyl silica(ODS)medium-pressure column chromatography(MPLC)and semi-preparative high-performance liquid chromatography(HPLC).The obtained purified compounds were identified by high-resolution-electrospray-mass spectrometry(HRESI-MS),nuclear magnetic resonance spectroscopy(NMR)and literature data comparison.Results Nine compounds were isolated from Penicillium sp.LHW5975,including one new compound penicindoline A(1)and eight known compounds,which are 17-hydroxybrevianamide N(2),benzomalvin A(3),benzomalvin B(4),benzomalvin C(5),benzomalvin D(6),benzomalvin E(7),(−)-benzomalvin E(8),and N-methylnovobenzomalvin A(9).Proangiogenesis activity evaluation of the isolated compounds using zebra fish model showed that benzodiazepines 2 and 7 promoted the angiogenesis at the concentration of 50µg/mL.Conclusion Compound 1 is a new compound,and compound 2 and 9 are isolated from Penicillium sp.for the first time.Compound 2 and 7 have proangiogenesis activity.

关 键 词：青霉 生物碱 青霉吲哚碱甲 海洋天然产物 促血管生成活性 17-羟基短密青霉酰胺N 苯并玛尔维碱E 

分 类 号：R284.1[医药卫生—中药学]