海洋来源黄直丝链霉菌产物中新细胞周期抑制剂的研究  

A study on new cell-cycle inhibitors from the metabolites of marine-derived Streptomyces flavorectus

作　　者：王健[1] 崔承彬[1,2] 顾谦群[1] 朱伟明[1] 朱天骄[1] 刘红兵[1] 方玉春[1] 

机构地区：[1]教育部海洋药物重点实验室,山东省海洋药物重点实验室,中国海洋大学海洋药物与食品研究所,山东青岛266003 [2]军事医学科学院毒物药物研究所

出　　处：《中国海洋药物》2005年第4期1-5,共5页Chinese Journal of Marine Drugs

基　　金：国家973计划(G1998051113);国家自然科学基金(39825126;30171102;30472079);国家863计划(2001AA624020;2003AA624020);山东省自然科学基金重点(Z2001C01);山东省科技攻关计划(0121100107);国家教育部长江学者奖励计划等基金资助项目。

摘　　要：目的研究海洋来源黄直丝链霉菌Z4-007产物中的抗肿瘤活性成分。方法采用流式细胞术筛选模型与分离技术紧密结合的活性跟踪分离模式,以细胞周期抑制活性为抗肿瘤指标,分离纯化活性成分;根据理化常数及波谱数据鉴定化学结构;用流式细胞术测试化合物活性。结果从黄直丝链霉菌Z4-007发酵物中分离得到4个活性化合物,其中1个鉴定为1-(2,4-二羟基-3,5-二甲基苯基)-(2E,4E)-己二烯-1-酮(1),其余3个初步推测为环肽类化合物。用小鼠乳腺癌tsFT210细胞经用流式细胞术测试分析结果表明:化合物Ⅰ在高浓度时将细胞周期抑制在G0/G1期,而在低浓度时则抑制在G2/M期并显示出一定的细胞凋亡诱导活性。结论化合物Ⅰ为首次从链霉菌属的微生物产物中分离得到,是一个新的细胞周期抑制剂。Aim To explore the antitumor active metabolites of marine-derived Streptomyces flavorectus Z4-007. Methods The separation procedure was guided by a flow cytometric bioassay using tsFT210 cells to examine cell cycle inhibitory activity, and various column chromatography using silica gel, Sephadex LH-20, and ODS were employed for the isolation and purification of bioactive compounds. Chemical structures were investigated by spectroscopic methods and biological activities were evaluated by flow cytometry using mouse cancer tsFT210 cells. Results Four bioactive compounds were isolated from the fermentation broth of Streptomyces flavorectus Z4-007, one of them had been identified as 1-（2,4-Dihydroxy-3,5-dimethyl-phenyl）-hexa- （E,E）-2,4-dien-l-one （1） and the other three compounds were considered to be peptide, Compound Ⅰ inhibited the cell-cycle of tsFT210 cells at the G0/G1 phase at higher concentrations, while at the lower concentrations compound Ⅰ inhibited the cell-cycle mainly at the G2/M phase, accompanied with induction of apoptosis in the tsFT210 ceils. Conclusion Compound I was isolated from the metabolites of the genus Streptomyces for the first time and provided as a new cell-cycle inhibitor.

关 键 词：海洋放线菌 黄直丝链霉菌 细胞周期抑制剂 色谱分离 1-(2 4-二羟基-3 5-二甲基苯基)-(2E 4E)-己二烯-1-酮 抗肿瘤活性 

分 类 号：Q939.130.6[生物学—微生物学] R931.711[医药卫生—生药学]