1株海洋真菌Aspergillus sp. WHUF0313次级代谢产物及其活性研究

摘要：目的 研究1株深海来源曲霉属真菌Aspergillus sp. WHUF0313的次级代谢产物及其生物活性。方法 采用硅胶柱层析、Sephadex LH-20葡聚糖凝胶柱层析和半制备高效液相色谱等技术对该菌株的次级代谢产物分离纯化，并通过核磁共振波谱(NMR)、质谱(MS)等方法，结合相关文献对比鉴定化合物结构；分别采用肉汤微量稀释检测法和MTS细胞增殖与毒性检测法对化合物进行抗菌和肿瘤细胞毒活性测试。结果 从Aspergillus sp. WHUF0313的发酵产物共分离得到9个化合物，分别为asperophiobolin G(1)、asperophiobolin F(2)、ophiobolin Q(3)、asperophiobolin H(4)、6-epi-ophiobolin G(5)、ophiobolin H(6)、6-epi-ophiobolin K(7)、6-epi-21,21-O-dihydroophiobolin G(8)和asperophiobolin J(9)。结论 海洋真菌Aspergillus sp. WHUF0313能产生多种活性次级代谢产物，化合物4对小鼠黑色素瘤B16有一定的细胞毒活性，化合物6和7具有较强的抗多重耐药幽门螺杆菌和抗金黄色葡萄球菌活性，因此该菌具有开发为微生物源药物的潜在研究价值。

Bioactive secondary metabolites from a marine-derived fungus Aspergillus sp. WHUF0313

Abstract Objective To study the secondary metabolites and their activities from a marine-derived fungus Aspergillus sp. WHUF0313. Methods The silica gel column chromatography, SephadexLH-20 gel columnchromatography, and high-performance liquid chromatography (HPLC) were used to isolate and purify the secondary metabolites from the fermented extracts of the fungus Aspergillus sp. WHUF0313. Their structures were elucidatedon the basis of Nuclear Magnetic Resonance analyses (NMR) and Mass Spectrum (MS) spectroscopic data and bycomparison with the data of literatures. Their antibacterial and cytotoxic activities were evaluated by microdilutionassay and MTS assay, respectively. Results Nine compounds were isolated and identified as asperophiobolin G(1), asperophiobolin F (2), ophiobolin Q (3), asperophiobolin H (4), 6-epi-ophiobolin G (5), ophiobolin H (6), 6-epiophiobolinK (7), 6-epi-21,21-O-dihydroophiobolin G (8) and asperophiobolin J (9). Conclusion Many bioactivecompounds were produced by the marine-derived fungus Aspergillus sp. WHUF0313. Compound 4 exhibitedcytotoxic activity against malignant melanoma B16 cell lines. Compounds 6 and 7 exhibited antibacterial activitiesagainst multi-drug resistant strains Helicobacter pylori and Staphylococcus aureus. The fungus Aspergillus sp.WHUF0313 has potential research value in the development of microbial