产黄青霉S-3-25的硫酸二乙酯诱变突变株3d10-01的次级代谢产物研究Ⅱ  

The secondary metabolites isolated from a mutant 3d10-01 derived from Penicillium chrysogenum S-3-25 by diethyl sulfate mutagenesis II

作　　者：乔桦 徐锐 杨郁 岳贤琳 王紫临 陈波[3] 朱天骄[4] 崔承彬 张国刚[2] 李长伟 QIAO Hua;XU Rui;YANG Yu;YUE Xianlin;WANG Zilin;CHEN Bo;ZHU Tianjiao;CUI Chengbin;ZHANG Guogang;LI Changwei(State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China;Key Laboratory for Polar Science of State Oceanic Administration,Polar Research Institute of China,Shanghai 200136,China;Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China)

机构地区：[1]军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室,北京100850 [2]沈阳药科大学中药学院,辽宁沈阳110016 [3]中国极地研究中心国家海洋局极地科学重点实验室,上海200136 [4]中国海洋大学海洋药物教育部重点实验室,医药学院,山东青岛266003

出　　处：《中国海洋药物》2024年第4期1-11,共11页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(81573300)资助。

摘　　要：目的 阐明产黄青霉Penicillium chrysogenum S-3-25的硫酸二乙酯(DES)诱变突变株3d10-01的大米固体培养基发酵次级代谢产物及其细胞毒活性。方法 利用各种色谱技术分离纯化次级代谢产物,根据理化和波谱数据(核磁共振、质谱技术)鉴定化合物结构,采用3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)法评价细胞毒活性。结果 从真菌S-3-25硫酸二乙酯(DES)诱变突变株3d10-01的大米固体培养基发酵产物中分离鉴定了17个化合物:dehydroaustinol(1)、dehydroaustin(2)、austinol(3)、austinolide(4)、11-acetoxyisoaustinone(5)、penipyridone F(6)、penipyridone C(7)、penipyridone D(8)、1-羟基-3-甲基呫吨酮(9)、1,5-二羟基-3-甲基呫吨酮(10)、nidulalin B(11)、(4S,4a R,9a R)-4a-carbomethoxy-1,4,4a,9atetrahydro-4,8-dihydroxy-6-methylxanthone(12)、(4R,4a S,9a R)-1,9a-dihydronidulalin A(13)、1-羟基-3-羟甲基呫吨酮(14)、1,7-二羟基-3-甲基呫吨酮(15)、(S)-2-methyl-3-[(Z)-benzylidene] hexahydropyrrolo [1,2-a]pyrazine-1,4-dione(16)及pestalasin A(17)。其中化合物1、3、5、6、9、10、15对受试HL60细胞的半抑制浓度(IC50)分别为1.7、15.0、16.6、26.5、2.0、6.9和28.4μmol/L,此外化合物1对受试K562细胞和He La细胞的IC50分别为24.2和25.4μmol/L。结论 从极地深海来源真菌产黄青霉S-3-25的硫酸二乙酯(DES)诱变突变株3d10-01的大米固体培养基发酵产物中分离得到17个单体化合物,其中化合物10、16为新天然产物,未见有文献数据的报道。化合物1、3、5、6、9、10、15对受试HL60细胞有较强的抑制活性;化合物1还对K562和He La细胞有较强的抑制活性。Objective To investigate the secondary metabolites from diethyl sulfate(DES)mutant 3d10-01 derived from Penicillium chrysogenum S-3-25 isolated from polar deep sea fermented in artificial seawater medium.Methods The secondary metabolites were isolated by multiple separation techniques,the structures of the compounds were identified according to the physicochemical and spectral data(nuclear magnetic resonance and mass spectrometry),the cytotoxic activities were assayed by MTT method.Results Seventeen metabolites:dehydroaustinol(1),dehydroaustin(2),austinol(3),austinolide(4),11-acetoxyisoaustin-one(5),penipyridones F(6),penipyridones C(7),penipyridones D(8),1-hydroxy-3-methylxanthone(9),1,5-dihydroxy-3-methylxanthone(10),nidulalin B(11),(4S,4aR,9aR)-4a-carbomethoxy-1,4,4a,9a-tetrahydro-4,8-dihydroxy-6-methylxanthone(12),(4R,4aS,9aR)-1,9a-dihydronidulalin A(13),1-hydroxy-3-hydroxymethyl-9H-xanthen-9-one(14),1,7-dihydroxy-3-methylxanthone(15),(S)-2-methyl-3-[(Z)-benzylidene]hexahydropyrrolo[1,2-a]pyrazine-1,4-dione(16)and pestalasins A(17)were isolated and identified from its rice fermentation products.Compounds 1,3,5,6,9,10 and 15 displayed stronger cytotoxic activities against HL60 cells with the IC50 values of 1.7,15.0,16.6,26.5,2.0,6.9 and 28.4μmol.L?1.Compounds 1 also displayed stronger cytotoxic activities against K562 and Hela cells with the IC50 values of 24.2 and 25.4μmol.L-1.Conclusion Seventeen compounds were isolated from diethyl sulfate(DES)mutant 3d10-01 derived from the fungus Penicillium chrysogenum S-3-25.Compound 10 and 16 were new natural products and had never been reported in the literature.Compounds 1,3,5,6,9,10 and 15 displayed stronger cytotoxic activities against HL60 cells and compounds 1 also displayed stronger cytotoxic activities against K562 and Hela cells.

关 键 词：海洋来源真菌 产黄青霉 硫酸二乙酯(DES)诱变 突变株3d10-01 细胞毒 

分 类 号：R931.77[医药卫生—生药学]