海洋真菌烟曲霉H1-04生产的生物碱类化合物及其抗肿瘤活性  

Alkaloidal compounds produced by a marine-derived fungus,Aspergillus fumigatus H1-04,and their antitumor activities

作　　者：韩小贤[1,2] 许晓妍[3] 崔承彬[1] 顾谦群[3] 

机构地区：[1]军事医学科学院毒物药物研究所 [2]中国海洋大学教育部海洋药物重点实验室,山东青岛266003 [3]中国海洋大学教育部海洋药物重点实验室

出　　处：《中国药物化学杂志》2007年第4期232-237,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家重点基础研究发展规划项目(G1998051113&2006CB504100);国家高技术研究发展计划项目(2001AA624020/2003AA624020);国家自然科学基金项目(39825126;30171102;30472079;30572279)

摘　　要：目的研究海洋真菌烟曲霉H1-04（Aspergillus fumigatus H1-04）生产的抗肿瘤活性产物。方法以生物活性为导向．利用液液萃取、硅胶柱色谱、制备HPLC等技术分离纯化活性化合物；根据理化常数及波谱数据鉴定化学结构：采用SRB法和MTT法测试评价抗肿瘤活性。结果与结论从烟曲霉H1—04发酵物中分得7个化合物，分别鉴定为fumiquinazoline J（1）、fumiquinazoline F（2）、fumiquinazoline G（3）、fumiquinazoline C（4）、fumiquinazoline A（S）、tryptoquivaline J（6）和pseumtin A（7）。化合物1～7对小鼠乳腺癌tsFT210细胞均呈一定的细胞增殖抑制活性，1、4和7对人肝癌BEL-7402、人肺癌A549、人白血病HL60和小鼠白血病P388细胞也有不同程度的抑制活性。化合物1为首次从自然界分离获得，其抗肿瘤活性也属首次报道，化合物6为首次从海洋来源微生物产物中分离得到。Aim To investigate the antitumor metabolites of marine-derived Aspergillus fumigatus H1-04. Methods The isolation procedure was guided by a bioassay using tsFT210 cells and various means of chromatography including TLC, VLC, LC, and semi-preparative HPLC were employed for the purification of aimed bioactive metabolites. Structures of the isolated compounds were investigated by spectroscopic meth ods and antitumor activities were assayed using human lung carcinoma A549, human leukemia HL60, human hepatic carcinoma cell BEL-7402, mouse leukemia P388, and mouse mammary carcinoma tsFT210 cells by MTT（A549 and HL60） or SRB（BEL-7402, P388 and tsFT210） method. Results and conclusion Seven alkaloids were isolated from the metabolites of Aspergillus fumigatus H1-04 and identified as fumiquinazoline J（11）, fumiquinazoline F（2）, fumiquinazoline G（3）, fumiquinazoline C（4）, fumiquinazoline A（5）, tryptoquivaline J（6） and pseurotin A（7）, respectively. Compounds 1- 7 inhibited the proliferation of tsFT210 cells to a certain extent. Meanwhile, 1,4, and 7 also inhibited the proliferation of P388, HL60, A-549, and BEL-7402 cells. Fumiquinazoline J（1） was found occurring in nature for the first time in the present study and its antitumor property was also reported for the first time. Compound 6 was isolated from the metabolites of marine-derived microorganisms for the first time.

关 键 词：海洋真菌 烟曲霉H1-04 代谢产物 生物碱 分离鉴定 抗肿瘤活性 

分 类 号：R284[医药卫生—中药学]