深海来源淡紫拟青霉ZBY-1的代谢产物及其抗肿瘤活性

摘要

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 various 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 MTT method. Results Seven compounds were isolated from the metabolites of P. lilacinus ZBY-1 and identified as 9( 11)-dehydroergosterol peroxide(l) , ergosterol peroxide(2) , (22E, 24R)-5a,6a-epoxy-3p-hydroxyergosta-22-ene-7-one(3) , and cerebrosides A(4) , B(5) , C(6) and D(7) , respectively. Compounds 1-3 inhibited the human cancer K562, MCF-7, HL-60 and BGC-823 cells and their IC50 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 metabolites 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.%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.