海洋真菌分离及菌株Aspergillus versicolor ZLQ-43的次级代谢产物的研究D

目的 对来源于渤海地区样品进行海洋真菌分离，并深入研究目标菌株杂色曲霉Aspergillus versicolor ZLQ-43的抗肿瘤活性成分。方法 采用稀释涂布平板法进行海洋真菌的分离；应用溶剂萃取，TLC分析，柱色谱层析及制备HPLC等方法对菌株ZLQ-43的发酵产物进行研究；通过理化性质及波谱学方法并参阅文献进行化学结构鉴定；采用CPE MTT法评价其抗H1N1流感病毒活性，采用SRB法评价其抗肿瘤的活性。结果 从渤海地区样品中最终筛选分离到海洋真菌90株，从菌株ZLQ-43发酵提取物中分离得到聚酮类化合物6个，经结构鉴定分别为sterigmatocystin (1), dihydrosterigmatocystin (2), vericolorin B (3), paeciloquinone C (4), versiconol (5)和2,4-dihydroxy-6-((R)-4-hydroxy-2-oxopentyl)-3-methylbenzaldehyde (6)。化合物4、6具有中等强度的抗H1N1病毒活性，抑制率分别为67.6%和51.5%；化合物5在1 mg?mL-1浓度下对P388细胞增殖抑制率67.79%。 结论 菌株ZLQ-43能够产生结构多样的活性次级代谢产物，发现化合物1、3、5具有P388细胞增殖抑制活性，并首次报道化合物4、6的抗H1N1病毒活性。

Isolation of marine-derived fungi and studies on the secondary metabolites of strain Aspergillus versicolor ZLQ-43

Objective To isolate fungi strains from marine sediments and study on the secondary metabolites of one marine-derived strain Aspergillus versicolor ZLQ-43. Methods Fungi were isolated by dilution-plate method and their extract were purified by solvent extraction, TLC analysis, column chromatography and preparative HPLC. The structures were established by physicochemical properties and spectral analysis, and comparison with the data of literatures. The proliferation inhibition activities were evaluated by SRB method, and antivirus activity were evaluated by CPE and MTT methods. Results The ninety fungi strains were isolated from the marine samples, and six polyketide compounds were isolated from ZLQ-43. Their structures were identified as sterigmatocystin (1), dihydrosterigmatocystin (2), vericolorin B (3), paeciloquinone C (4), versiconol (5), 2,4-dihydroxy-6-((R)-4- hydroxy-2-oxopentyl)-3-methyl benzaldehyde (6). Compounds 4 and 6 exhibited activity against influenza virus A (H1N1) with inhibition rate of 67.6% and 51.5% , respectively, while at the concentration of 1 mg.mL_-1 , compound 5 exhibited moderate activities against p388 cell line with inhibition rate of 67.79%. Conclusion The fungal strain ZLQ-43 was found to be a producer of diverse secondary metabolites, and report the activity on P388 of compounds 1, 3, 5,the activity against H1N1 virus of compounds 4 and 6, firstly.