极地真菌Geomyces pannorum SA3-2-YM次级代谢产物的研究

Study on the secondary metabolites of polar region-derived fungus Geomyces pannorum SA3-2-YM

采用聚酰胺柱层析、硅胶柱层析、反相硅胶柱层析、凝胶柱层析和高效液相HPLC等色谱技术,对极地真菌Geomyces pannorum SA3-2-YM的发酵液提取物进行分离纯化,共得到13个化合物,通过NMR和MS等波谱数据确定结构为:cyclo-(L-Trp-L-Pro)(1)、cyclo-(L-Trp-L-Tyr)(2)、cyclo-(Gly-L-Trp)(3)、cyclo-(L-Trp-L-Phe)(4)、cyclo-(L-Trp-L-Ser)(5)、cyclo-(L-Tyr-L-Pro)(6)、cyclo-(L-Trp-L-Ile)(7)、cyclo-(D-Ala-D-Trp)(8)、ergosterol(9)、(22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol(10)、anicequol(11)、indazole(12)、p-hydroxybenzaldehyde(13)。其中,化合物1~9、11~13均为首次从地丝霉属的真菌中分离得到。抑菌试验表明化合物9对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌具有一定的抑制活性,其最小抑制浓度(MIC)均为90μg/mL。采用CCK-8法测试了13个化合物对四种肿瘤细胞株的体外细胞毒活性,化合物1~13对四株实验肿瘤细胞株表现出不同程度的抑制活性,其中环二肽化合物8对HeLa肿瘤细胞的抑制率可达62.28%,含有过氧基团的化合物10对SMMC-7721细胞的抑制率达到了68.13%。

By means of various kinds of column chromatography and semi-preparative high performance liquid chromatography(SP-HPLC),thirteen compounds were obtained from the fermentation of polar region-derived fungus Geomyces pannorum(SA3-2-YM).Their structures were identified as cyclo-(L-Trp-L-Pro)(1),cyclo-(L-Trp-L-Tyr)(2),cyclo-(Gly-L-Trp)(3),cyclo-(L-Trp-L-Phe)(4),cyclo-(L-Trp-L-Ser)(5),cyclo-(L-Tyr-L-Pro)(6),cyclo-(L-Trp-L-Ile)(7),cyclo-(D-Ala-D-Trp)(8),ergosterol(9),(22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol(10),anicequol(11),indazole(12),p-hydroxybenzaldehyde(13)on the basis of NMR and MS spectroscopic data.Compounds 1-9,11-13 were isolated from the genus Geomyces for the first time.The antimicrobial activities showed that compound 9 showed weak antibacterial activities against Escherichia coli,Staphylococcus aureus and Bacillus subtilis with minimum inhibitory concentration(MIC)value of 90μg/mL,respectively.The cytotoxic activities against four tumor cell lines of 13 compounds were evaluated by cell counting kit-8(CCK-8)assay,compounds 1-13 showed different degrees of inhibitory activities against HeLa,HepG2,MCF-7 and SMMC-7721.Among them,the inhibition rates of cyclodipeptide compound 8 against HeLa and compound 10 containing peroxy group against SMMC-7721 were 62.28%and 68.13%,respectively.