摘要
目的研究海洋来源真菌烟曲霉H1-04（Aspergillus fumigatusH1-04）发酵液中的抗肿瘤活性产物。方法采用液液萃取、硅胶柱色谱、制备HPLC等技术,从烟曲霉H1-04的发酵产物中分离纯化活性产物。活性产物的结构经IR、MS、^1H-NMR确证。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发酵物中分离鉴定了4个硫代二酮哌嗪类化合物,分别是胶霉毒素（gliotoxin,1）、bisdethiobis（methylthio）gliotoxin（2）、bis-N-norgliovictin（3）、didehydrobisdethiobis（methylthio）gliotoxin（4）。化合物1在浓度为0.1μmol·L^-1时几乎能完全抑制小鼠白血病P388细胞和人肺癌A549细胞的增殖,抑制率分别为100%和99.1%;对小鼠乳腺癌tsFT210细胞也呈现很强的细胞凋亡诱导、细胞周期抑制、坏死性细胞毒等活性。化合物2-4对tsFT210细胞显示出不同程度的抗肿瘤活性。化合物2-4为首次从烟曲霉发酵物中分离得到,并首次报道2-4的抗肿瘤活性。
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 compounds were investigated by the spectroscopic methods and antitumor activities were assayed using human cancer A549, mouse cancer P388, and tsFT210 cells by MTT （A549） or SRB （P388 and tsFT210） method. Results and conclusion Four diketopiperazines 1- 4 were isolated from the metabolites of Aspergillus fumigatus H1-04 and they were identified as gliotoxin （1）, bisdethiobis （methylthio） gliotoxin （2）, bis- N-norgliovictin （3） and didehydrobisdethiobis （methylthio） gliotoxin（4）, respectively. Compound 1 almost completely inhibited the proliferation of P388 （ 100 % ） and A549（99.1%） cells at 0.1 μmol·L^-1 and showed also strong cytotoxicity against tsFT210 cells. Compounds 2 - 4 inhibited the proliferation of tsFT210 cells to different extent. Compounds 2 - 4 were isolated from the metabolites of the fungal species Aspergillus fumigatus for the first time and their antitumor properties were also reported for the first time.
出处
《中国药物化学杂志》
CAS
CSCD
2007年第3期155-159,165,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)
山东省自然科学基金重点项目(Z2001C01)
山东省科技攻关计划项目(0121100107)
青岛市自然科学基金项目(04-2-JZ-81)
国家教育部长江学者奖励计划基金项目
关键词
海洋真菌
烟曲霉H1-04
代谢产物
二酮哌嗪
结构鉴定
抗肿瘤活性
marine-derived fungus
Aspergillus fumigatus H1-04
secondary metabolite
diketopiperazine
structural identification
antitumor activity
