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

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.