葡萄穗霉属真菌Stachybotrys sp.CPCC 401591的抗肿瘤活性次级代谢产物

Secondary metabolites exhibiting antitumor bioactivities from the fungus Stachybotrys sp.CPCC 401591

以葡萄穗霉属真菌Stachybotrys sp.CPCC 401591为研究对象,对其次级代谢产物进行化学分离并评价单体化合物抗肿瘤活性。采用溶剂萃取、正相硅胶柱、反相硅胶柱以及半制备高效液相色谱等分离技术,对目标菌株CPCC401591发酵产物的乙酸乙酯提取相进行以抗肿瘤活性为导向的化合物分离纯化。根据理化性质、波谱数据分析以及文献检索比对,共分离鉴定了6个单体化合物,分别为satratoxin G(1)、mytoxin A(2)、12′-hydroxyroridin E(3)、roridin E(4)、4-acetoxy-12,13-epoxy-9-trichothecene(5)和arthproliferin A(6)。其中,化合物1–5为单端霉烯类化合物,化合物6为聚酮类杂萜化合物。采用CCK-8比色法对化合物1-6的抗肿瘤活性进行测试。测试结果显示,化合物1-6对人宫颈癌细胞HeLa和人乳腺癌细胞MCF-7具有非常显著的抑制活性,化合物4-5对人肺癌细胞A549具有较好的抑制作用。该研究为从葡萄穗霉属类真菌发现更多的抗肿瘤活性分子提供了依据和思考。

The components exhibiting anti-tumor bioactivity were isolated from the fermentation crude extract of the fungus Stachybotrys sp.CPCC 401591.Purification of anti-tumor bioactivityguided compounds was performed.The routine separation approaches for purification included ethyl acetate extraction,silica gel column chromatography and preparative HPLC.Six compounds were obtained and their structures were elucidated as satratoxin G(1),mytoxin A(2),12′-hydroxyroridin E(3),roridin E(4),4-acetoxy-12,13-epoxy-9-trichothecene(5),and arthproliferin A(6)by analysis of spectroscopic data including NMR and mass spectrometry analysis.Among six compounds identified,compounds 1−5 were trichothecene derivatives,while compound 6 was polyketide-derived meroterpenoid.The cytotoxic activity of the compounds 1−6 was evaluated by CCK-8 assay in vitro.The results showed that compounds 1−6 displayed significant inhibition activities on human cervical cancer cells HeLa and human breast cancer cells MCF-7.Additionally,compounds 4−5 could inhibit human lung cancer cells A549 with moderate activities.Our report provides foundation for mining Stachybotrys species for more new anti-tumor compound or drug leads.