【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。更多还原

【Abstract】 Aim To investigate the antitumor agents produced by marine-derived Penicillium flavidorsum SHK1-27.Methods The producing strain SHK1-27 was fermented in a rotary shaker and bioactive metabolites in the fermentation broth were isolated through a bioassay-guided separation procedure.Structures of the bioactive compounds were investigated by spectroscopic methods and their in vitro antitumor activities were assayed by the SRB method using K562 cells.Results Eight anthraquinone derivatives were isolated from the fermentation broth of P.flavidorsum SHK1-27 and were identified as nidurufin(1),averufin(2),8-O-methylaverufin(3),6,8-O-dimethylaverufin(4),versicolorin B(5),versicolorin A(6),versiconol(7) and averantin(8),respectively.Compounds 1-8 inhibited the proliferation of K562 cells and could be classified as strong(1 and 8 with the IC50 values of 12.6 and 27.7 μmol·L-1 respectively),moderate(2,5,6 and 7 with the IC50 values of 72.4,91.0,98.7 and 93.4 μmol·L-1 respectively)and weak(3 and 4 both with the same IC50 value of>100 μmol·L-1)activity groups,respectively.The results showed some structure-activity relationships.Conclusion This is the first report of compounds 18 as the secondary metabolites of P.flavidorsum species,1,5 and 6 were isolated from fungal metabolites of the genus Penicillium for the first time,and 7 was found to occur in nature for the first time.The antitumor activities of compounds 1-8 on K562 cells were also reported for the first time in the present study.更多还原