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  

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

作　　者：乔桦 陈波[3] 朱天骄[4] 张国刚[1] 李长伟[2] 崔承彬[2] 

机构地区：[1]沈阳药科大学中药学院,沈阳110016 [2]军事医学科学院毒物药物研究所,北京100850 [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]中国海洋大学医药学院、海洋药物教育部重点实验室,青岛266003

出　　处：《国际药学研究杂志》2017年第9期871-877,共7页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金资助项目(81573300);国家“重大新药创制”科技重大专项资助项目(2012ZX09301-003)

摘　　要：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HPLCUV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 3 d10-01 derived from Penicillium 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-trimethylbenzoate（1）,6-hydroxymethyl-2,2-dimethylchromanone（2）,regiolone（3）,（3 S,4 S）-3,4-dihydro-3,4,8-trihydroxy（2 H）naphthalenone（4）,cerebroside C（5）,cerebroside D（6）and dankasterone A（7）,were isolated from the fermentation products of the mutant 3 d10-01.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 3 d10-01.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 reported for the first time.

关 键 词：极地深海来源真菌 产黄青霉S-3-25 硫酸二乙酯(DES)诱变 突变株3d10-01 抗肿瘤活性 

分 类 号：R915[医药卫生—微生物与生化药学]