深海来源淡紫拟青霉ZBY-1的代谢产物及其抗肿瘤活性  

Metabolites of Paecilomyces lilacinus ZBY-1 from deep-sea water and their antitumor activity

作　　者：崔香[1,2] 李长伟[2] 吴长景[2] 华威[2] 崔承彬[2] 朱天骄[3] 顾谦群[3] 

机构地区：[1]中南大学药学院,长沙410013 [2]军事医学科学院毒物药物研究所,北京100850 [3]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》2013年第2期177-186,共10页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金项目(81172976,30973631);国家高技术研究发展计划(863计划)资助项目(2013AA092901);国家科技重大专项资助项目(2012ZX09301-003)

摘　　要：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。方法采用活性跟踪分离模式,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结合部分化合物的甲醇解反应鉴定化合物结构;采用MTT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9(11)-去氢过氧化麦角甾醇(1)、过氧化麦角甾醇(2)、(22E,24R)-5α,6α-环氧-3β-羟基麦角甾-22-烯-7-酮(3)和脑苷脂A(4)、B(5)、C(6)、D(7)等7个化合物。化合物1～3对人癌细胞K562、MCF-7、HL-60、BGC-823有较强抑制作用,IC50在9.5～59.6 mg/L之间,而4～7对上述4种癌细胞均无抑制活性。结论本文是有关深海来源淡紫拟青霉代谢产物的首篇研究报道。化合物1～7为首次从淡紫拟青霉产物中分离得到,其中1和3首次从拟青霉属、3还首次从真菌中分离报道。化合物1对K562和BGC-823细胞以及3对上述4种癌细胞的抑制活性亦属首次测试报道。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 and the metabolites were isolated by va- rious chromatographic means. Compounds were identified on the basis of their physicochemical and spectroscopic data coupled with the methanolysis of several compounds. The antitumor activity was assayed by the MTI＂ method. Results Seven compounds were isolated from the metabolites of P. lilacinus ZBY-1 and identified as 9 （ 11 ） -dehydroergosterol peroxide （ 1 ）, ergosterol peroxide （2）, （ 22E, 24R）-So~,6c^-epoxy-3[^-hydroxyergosta-22-ene-7-one（3）, and cerebrosides A（4）, B（$）, C（6） and D（7）, respectively. Compounds 1-3 inhibited the human cancer K562, MCF-7, HL-60 and BGC-823 cells and their ICs0 values on these cell lines ranged from 9. 5 to 59.6 mg/L, while compounds 4-7 showed no inhibitory effect on the above four cancer cell lines. Conclusions This paper is the first report on the metabolites of P. lilacinus from the marine environment. For the first time, compounds 1-7 were isolated from the metabo- lites of P. lilacinus, with 1 and 3 from the genus Paecilomyces, and 3 from the fungi, respectively. The inhibitory effect of 1 on the K562 and BGC-823 cells and 3 on the above four cancer cell lines were also assayed for the first time.

关 键 词：深海海水来源真菌 淡紫拟青霉ZBY-1 次级代谢产物 抗肿瘤活性 甾类 脑苷脂 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学]