天然产物研究与开发 ›› 2016, Vol. 28 ›› Issue (12): 1864-1869.doi: 10.16333/j.1001-6880.2016.12.002

• 研究论文 • 上一篇    下一篇

采用OSMAC法对Streptomyces roseofulvus M63次级代谢产物及其抗肿瘤成分的研究

关永强1,罗影2,石磊岭1,古丽娜·沙比尔1,陈刚1,郭雄飞1,罗都强3*   

  1. 1新疆维吾尔自治区中药民族药研究所;2新疆农业科学院植物保护研究所,乌鲁木齐 830002;3河北大学生命科学学院,保定 071002
  • 出版日期:2016-12-31 发布日期:2017-03-31

Isolation of Secondary Metabolites from Streptomyces roseofulvus M63 by OSMAC Methods and Their Anti-tumor Activity

GUAN Yong-qiang1,LUO Ying2,SHI Lei-ling1,GULINAR Sabir1,CHEN Gang1,GUO Xiong-fei1,LUO Du-qiang3*   

  1. 1 Xinjiang Institute of Chinese Material Medical and Ethica;2Xinjiang Academy of Agricultural  Sciences,Urumqi 830001,China;3Colloge of Life Science,Hebei University,Baoding 071002,China
  • Online:2016-12-31 Published:2017-03-31

摘要: 本文采用OSMAC方法通过4种发酵方式从玫瑰黄链霉菌Streptomyces roseofulvus M63中获得其次级代谢产物,并研究它们的抗肿瘤活性。首先应用正相硅胶柱色谱、薄层色谱、羟丙基葡聚糖凝胶Sephadex LH-20、反向硅胶、制备色谱等多种方法进行分离纯化,其次用NMR和MS等波谱技术解析化合物的结构,最后采用MTT法筛选具有抗肿瘤活性的化合物。从玫瑰黄链霉菌M63中共分离鉴定出14个化合物,分别为对甲基苯酚(1)、4-羟基苯乙醇(2)、2,3,4,5-四羟基苯甲基酯(3)、3,4-二羟基苯甲酸(4)、4-羟基苯甲酸(5)、1H-吡咯-2-羧酸(6)、(22E,24R)-麦角甾-7,22-二烯-3β-醇(7)、4-羟基苯甲醛(8)、3β-羟基-5α,8α-过氧化麦角甾-6,22-二烯(9)、4-羟基苯乙酸(10)、5-(2-甲基苯基)-4-戊烯酸(11)、3β-羟基-麦角甾-5,7,22-三烯(12)、(5-羟基-2-氧代-2H-吡喃-4-基)乙酸甲酯(13)、(4S,5S,9AR-5-(E)-4-羧基,甲基-8-烯)-10,13-二甲基-6-萘甲酸(14)。上述14个化合物均为首次从玫瑰黄链霉菌M63中分离得到,其中化合物11、13对子宫颈癌细胞(HeLa)、卵巢癌细胞(SKOV3)均有不同程度的抑制作用;化合物11在24h时的半抑制浓度值(IC50)低于阳性对照物顺铂,为38.26、14.25 μmol/mL;化合物13对HeLa细胞、Skov3细胞在24、48、72 h时半抑制浓度值(IC50)分别为25.62、11.34、6.524 μmol/mL;7.892、10.32、5.671 μmol/mL。

关键词: 玫瑰黄链霉菌, OSMAC方法, 次级代谢产物, 抗肿瘤活性

Abstract: In this study,secondary metabolites of Streptomyces roseofulvus M63 were obtained under four fermentation ways using OSMAC methods,and their antitumor activity was examined.Compounds were firstly isolated and purified by column chromatography on Silica gel,Silica gel thin layer chromatography, Sephadex LH-20,reverse phase silica gel and preparative chromatography.The structures of purified compounds were identified by NMR and MS.Their antitumor activity was eventually evaluated using MTT method.The results showed that,fourteen compounds were purified and identified as p-cresol(1),4-hydroxyphenyl ethanol (2),2,3,4,5-tetra hydroxy,methyl ester(3),3,4-dihydroxy benzoic acid(4),4-hydroxy benzoic acid(5),1H-Pyrrole-2-carboxylic acid(6),(22E,24R)-Ergosta-7,22-dien-3β-ol (7),4-hydroxy benzaldehyde (8),3β-hydroxy-5α,3β-hydroxy-5α,8α-ergosterol peroxide-6,22-diene(9),4-hydroxy phenylacetic (10),5-(2-Methylphenyl)-4-penten oic acid(11),3β-hydroxy-ergosterol-5,7,22-triene(12),(5-hydroxy-2-oxo-2H-pyran-4-yl) acetate (13),(4S,5S,9aR)-5-(E)-4carboxy methyl-8-en)-10,13-dimethyl-6- deca hydrronaphthalene-carboxylic acid(14).It was the first time to obtainthese compounds from Streptomyces roseofulvus M63,cervical cancer (HeLa) cells and ovarian cancer(Skov3)were inhibited by compound 11,13 for different degrees.The IC50 values of compound 11 was 38.26 and 14.25 μmol/mLthat less thanpositive control cisplatin only at 24h.The IC50 values of compound 13 on HeLa cells and Skov3 cells was 25.62,11.34,6.524 and 7.892,10.32,5.671,at 24 h,48 h and 72 h,respectively.

Key words: Streptomyces roseofulvus, OSMAC method, secondary metabolites, anti-tumor activity

中图分类号: 

R979.1