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目的阐明海洋真菌链孢粘帚菌(Gliocladium catenulatum T31)的抗肿瘤活性次级代谢产物。方法摇床发酵培养生产菌T31,活性跟踪分离纯化T31发酵液中的活性单体化合物,并根据理化性质和光谱分析(ESI MS、UV、IR、NMR等)鉴定单体化合物结构;采用细胞形态镜检、MTT方法评价单体化合物对人类慢性髓性白血病K562细胞的抗肿瘤活性。结果从链孢粘帚菌(Gliocladium catenulatum T31)发酵液中分离并鉴定了7个单体化合物,分别为3个甾醇类化合物ergosta-5,7,22-triene-3β-ol(1)、ergosta-6,22-diene-3β-ol(2)、ergosterol peroxide(3)和四个蒽醌类化合物emodin(4)、citreorosein(5)、isorhodopti-lometrin(6)和lunatin(7),化合物1~7对K562细胞显示不同程度的细胞增殖抑制活性,其中,化合物4~7对K562细胞的IC50分别为1.09、1.24、13.6和8.92μmol.L-1。结论海洋真菌链孢粘帚菌(Gliocladium catenulatumT31)的主要抗肿瘤活性次级代谢物是甾醇类和蒽醌类化合物。
Objective To elucidate the antitumor secondary metabolites of marine fungus Gliocladium catenulatum T31. Methods The active compound of T31 was isolated and purified from the fermentation broth by shaking flask fermentation. The structure of the monomer compounds was identified by the physico-chemical properties and spectral analysis (ESI MS, UV, IR, NMR, etc.) Microscopic examination and MTT method were used to evaluate the antitumor activity of monomeric compounds on human chronic myeloid leukemia K562 cells. Results Seven monomer compounds were isolated from the fermentation broth of Gliocladium catenulatum T31 and were identified as ergosta-5,7,22-triene-3β-ol (1) (2), ergosterol peroxide (3) and four anthraquinones emodin (4), citreorosein (5), isorhodopti-lometrin (6) and lunatin ~ 7 showed different degrees of cell proliferation inhibitory activity on K562 cells. IC50 of compound 4 ~ 7 on K562 cells were 1.09,1.24,13.6 and 8.92μmol.L-1, respectively. Conclusion The main anti-tumor activity secondary metabolites of marine fungus Gliocladium catenulatum T31 are sterols and anthraquinones.