目的 阐明产黄青霉S-3-25的硫酸二乙酯(DES)诱变突变株3d10-01的次级代谢产物及其抗肿瘤活性.方法 利用各种色谱技术分离纯化代谢产物.根据理化和波谱数据鉴定化合物结构.采用MTT法测试其抗肿瘤活性.采用HPLC-UV检测方式确定所得化合物是否为突变株新产.结果 从突变株发酵产物中分离鉴定了2,4-二羟基-3,5,6-三甲基苯甲酸甲酯(1),6-羟甲基-2,2-二甲基-苯并二氢吡喃-4-酮(2),regiolone(3),(3S,4S)-3,4-二氢-3,4,8-三羟基-2H-萘酮(4),脑苷脂C(5),脑苷脂D(6)和dankasterone A(7)7个化合物.化合物1、4和7对受试5种癌细胞均有较强抑制作用;2、3和6对受试HL-60细胞有一定抑制活性.HPLC-UV的检测结果表明,化合物1～4和7为原始菌不产而突变株新产的次级代谢产物.结论 化合物1～7均为首次从产黄青霉发酵产物中分离得到.化合物1～4、6和7对部分受试肿瘤细胞的抑制活性为首次研究并报道.%Objective To investigate the secondary metabolites from diethyl sulfate(DES)mutant 3d10-01 derived from Peni-cillium chrysogenum S-3-25. Methods The secondary metabolites were isolated by multiple separation techniques,such as silica gel,Sephadex LH-20 column chromatography and HPLC. The structures of the compounds were determined by ESI-MS and NMR spectroscopic data. The antitumor activity was assayed by the MTT method. HPLC-UV analysis was used to determine if compounds 1-7 were newly produced by the mutant. Results Seven secondary metabolites,including methyl 2,4-dihydroxy-3,5,6-trimethylbenzo-ate(1),6-hydroxymethyl-2,2-dimethylchromanone(2),regiolone(3),(3S,4S)-3,4-dihydro-3,4,8-trihydroxy(2H)naphthalenone (4),cerebroside C(5),cerebroside D(6)and dankasterone A(7),were isolated from the fermentation products of the mutant 3d10-01. Compounds 1,4 and 7 showed strong inhibitory effects on the five tested cell lines,but 2,3 and 6 only exhibited the proliferation of HL-60 cells to some extent. Compounds 1-4 and 7 were newly produced by the mutant 3d10-01. Conclusion Compounds 1-7 are firstly isolated from P. chrysogenum. The inhibitory effects on certain tested antitumor cell lines of compounds 1-4,6 and 7 are report-ed for the first time.
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