淡紫拟青霉ZBY-1的次级代谢产物及其抗肿瘤活性

Secondary metabolites of Paecilomyces lilacinus ZBY-1 and their antitumor activity

目的阐明来自深海海水的淡紫拟青霉ZBY-1的代谢产物及其抗肿瘤活性。方法采用活性跟踪模式分得活性组分，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MTF法测试抗肿瘤活性。结果从淡紫拟青霉ZBY．1发酵产物中分离鉴定了paecilaminol（1）、paecilaminol盐酸盐（2）、1（2）-linolyl-2（1）-palmityl—glycero—04’-（N，N，N．trimethyl）homoserine（3）、1，2-dilinolylglycero—O-4’-（N，N，N—tfimethyl）homoserine（4）、肉豆蔻酸甲酯（5）、亚油酸甲酯（6）、亚油酸（7）、油酸（8）、3-吲哚甲醛（9）、3一吲哚甲酸（10）和对羟基苯甲酸（11）等11个化合物。化合物1和2对4种人癌细胞有较强的抑制作用，IC50值为1．12～8．63μmol／L，且2对该4种人癌细胞的抑制活性是1的2．2—2．7倍。结论化合物1—11为首次从淡紫拟青霉产物中分离得到，其中3、4和9—11还系首次从拟青霉属分离报道。化合物1是菌株ZBY-1的主要抗肿瘤活性产物。本文首次报道1和2对人癌细胞的抑制活性。

Objective To investigate the metabolites of Paecilomyces lilacinus ZBY-1 isolated from a deep-sea water sample and test their antitumor activity. Methods The separation procedure was guided by a bioassay to obtain fractions with antitumor activi- ty and the metabolites in the bioactive fractions were isolated by various chromatographic means. Compounds obtained were identified by physicochemical and spectroscopic data. The antitumor activity was assayed by the M＇I＇r method. Results Eleven compounds 1-11 were isolated from the metabolites of P. lilacinus ZBY-1 and identified as paecilaminol（1）, paecilaminol hydrochlorate（2）, 1 （2）-li- nolyl-2（ 1 ） -palmityl-glycero-O-4＇-（N,N,N-trimethyl）homoserine（3）, 1,2-dilinolylglycero-O-4＇-（N,N,N-trimethyl） homoserine（4）, methyl myristate （ 5 ）, methyl linoleate （ 6 ）, linoleate （ 7 ）, oleinic acid （ 8 ）, indole-3-carboxaldehyde （ 9 ）, indolyl-3-carboxylic acid （10）, and 4-hydroxybenzoic acid （11）, respectively. Among them, compound 2 seemed to be an artificial byproduct of 1. Compounds 1 and 2 inhibited the human cancer K562, MCF-7, HL-60 and BGC-823 cells lines with the ICs0 values ranging from 1.12 to 8.63 μmol/L, and the inhibitory effect of 2 on these four cell lines were approximately 2. 2-2. 7 times of 1. Conclusions Compounds 1-11 were isolated from the metabolites of P. lilacinuz for the first time. Furthermore, 3, 4 and 9-11 were also obtained from the genus Paecilornyces for the first time. Compound 1 was a major antitumor metabolite of the strain ZBY-1 and the inhibitory effect of I and 2 on human cancer cell lines was recorded for the first time.