目的 研究蛇足石杉Huperzia serrata内生真菌Penicillium chrysogenum MT-40的代谢产物。方法 利用硅胶、Sephadex LH-20及半制备液相色谱等方法进行分离纯化，根据化合物的理化性质及IR、MS、NMR等数据鉴定化合物的结构；利用体外模型进行抑制血小板ATP释放及抗乙酰胆碱酯酶活性筛选。结果 从P.chrysogenum MT-40固体发酵培养后的代谢产物中分离得到了20个化合物，分别鉴定为(±)-N-(3a,4,5,6,7,8,9,10,11,12,13,13a-dodecahydrocyclododeca[d]oxazol-2-yl)-4-hydroxybenzamide（1）、cyclo-(Trp-Tyr)（2）、cyclo-(Trp-Phe)（3）、meleagrin（4）、alternariol（5）、alternariol methyl ether（6）、altenuene（7）、koninginin B（8）、koninginin F（9）、koninginin D（10）、过氧化麦角甾醇（11）、β-谷甾醇（12）、volemolide（13）、4-hydroxy-17R-methylincisterol（14）、4-hydroxy-3,6-dimethyl-2H-pyran-2-one（15）、对羟基苯甲酸（16）、对羟基苯甲醛（17）、香草酸（18）、对羟基苯乙酸（19）、酪醇（20）。结论 化合物1为新化合物，命名为(±)-盘尼西碱A；化合物5在100 μmol/L时有一定的抑制血小板释放ATP作用，抑制率为（40.6±5.2）%；所有化合物在100 μmol/L时未表现出乙酰胆碱酯酶抑制活性。

Objective To investigate the chemical metabolites from Penicillium chrysogenum MT-40, an endophytic fungus isolated from Huperzia serrata. Methods The compounds were isolated and purified by using various column chromatographies including silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were established using extensive spectroscopic techniques such as IR, MS, and NMR. The inhibitory activities against ATP release of platelets and acetylcholinesterase of all the isolates were also investigated by using in vitro models. Results Twenty compounds including (±)-N-(3a,4,5,6,7,8,9,10,11,12,13,13a- dodecahydrocyclododeca[d]oxazol-2-yl)-4-hydroxybenzamide (1), cyclo-(Trp-Tyr) (2), cyclo-(Trp-Phe) (3), meleagrin (4), alternariol (5), alternariol methyl ether (6), altenuene (7), koninginin B (8), koninginin F (9), koninginin D (10), ergosterol peroxide (11), β-sitosterol (12), volemolide (13), 4-hydroxy-17R-methylincisterol (14), 4-hydroxy-3,6-dimethyl-2H-pyran-2-one (15), p-hydroxybenzoic acid (16), 4-hydroxybenzaldehyde (17), 4-hydroxy-3- methoxybenzoic acid (18), 4-hydroxyphenylacetic acid (19), and tyrosol (20) were isolated from the solid fermentation cultures of P. chrysogenum MT-40. Conclusion Compound 1 is a new compound; Compound 5 exhibited slight inhibitory activities on ATP release of thrombin-activated platelets with inhibition rate of (40.6 ±5.2)% at the concentration of 100 μmol/L. All the compounds didn't exhibit inhibitory activities on AChE at the concentration of 100 μmol/L.

R284.1

基金项目:国家自然科学基金项目(81773842);国家自然科学基金项目(81903495);北京中医药大学新教师启动基金项目(2021-JYB-XJSJJ-005)