丰肉结海绵相关真菌产黄青霉HLS111菌株活性代谢产物研究  

Bioactive metabolites isolated from the fungus Penicillium chrysogenum HLS111 associated with the marine sponge Gelliodes carnosa

作　　者：巩婷[1] 孙传英[2] 甄心 邱君志[2] 杨金玲[1] 朱平[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室/国家卫生和计划生育委员会天然药物生物合成重点实验室,北京100050 [2]福建农林大学生命科学学院,福州350002

出　　处：《中国医药生物技术》2014年第3期174-179,共6页Chinese Medicinal Biotechnology

基　　金：国家"十二五"科技重大专项"综合性新药研究开发技术大平台"(2012ZX09301002-001-005);中央高校基本科研业务费(2012N06);天然药物活性物质与功能国家重点实验室自主课题C类课题(GTZC201215)

摘　　要：目的对我国南海水域丰肉结海绵相关真菌产黄青霉菌HLS111的活性代谢产物进行研究。方法采用HPLC-DAD技术与活性筛选相结合的方法,通过硅胶柱、凝胶柱及HPLC等色谱方法对HLS111发酵产物进行分离纯化;通过核磁共振、质谱等波谱分析手段对分离得到的化合物进行结构鉴定;并对单体化合物进行抗肿瘤、抗HIV、抗炎活性测定。结果分离得到12个化合物。其中2个黑麦酮酸类化合物:黑麦酮酸F(1)和D(2);4个生物碱类化合物:环(L-色氨酸-L-苯丙氨酸)(3)、citreoindole(4)、meleagrin(5)、脑苷脂B(6);4个甾体类化合物:麦角甾醇(7)、(22E,24R)-5α,8α-过氧化麦角甾-6,22-烯-3β-醇(8)、globosterol(9)、β-谷甾醇(10);1个三萜类化合物:24-亚甲基环木菠萝烷醇-反式阿魏酸(11);1个蒽醌类化合物:大黄素(12)。对化合物4的氢谱、碳谱数据进行了归属。初步的药理研究表明,黑麦酮酸类化合物表现出较强的抗肿瘤活性,化合物citreoindole表现出一定的抗HIV及抗炎活性。结论海绵相关真菌产黄青霉HLS111菌株体现了次生代谢产物化学结构的多样性;黑麦酮酸类化合物为产黄青霉HLS111的主要抗肿瘤活性成分。Objective To study the active metabolites produced by the fungus Penicillium chrysogenum HLS111 isolated from the marine sponge Gelliodes carnosa collected from the South China Sea. Methods Based on the technique of high performance liquid chromatography-diode array detector （HPLC-DAD） and the bioactive screening, chemical isolation and purification of the metabolites from the fermentation broth of the strain were conducted by means of silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC, etc. Their structures were elucidated by MS, NMR and other spectroscopic analysis. Their anti-tumor, anti-HIV, anti-inflammatory activities in vitro also were detected. Results Twelve metabolites were isolated, including two secalonic acids [secalonic acid F （1） and secalonic acid D （2）]; four alkaloids [cyclo （L-Tyr-L-Phe） （3）, citreoindole （4）, meleagrin （5）, cerebroside B （6）]; four steroids [ergosterol （7）, （22E,24R）-5α,8α-epidioxyergosta-6,22-dien-3β-ol （8）, globosterol （9）,β-sitosterol （10）];one triterpenoid [24-methylenecycloartanol trans-ferulate （11）], and one anthraquinone [emodin （12）]. The 1 H-NMR and 13C-NMR spectral data of compound 4 were assigned for the first time. Preliminary pharmacological studies showed that secalonic acids （1 and 2） exhibited strong antitumor activities, citreoindole （4） possessed moderate anti-HIV and anti-inflammatory activities. Conclusion The secondary metabolites isolated from marine fungus P. chrysogenum HLS111 are rich in structural types. Secalonic acids are the main antitumor components of this fungus.

关 键 词：青霉 产黄 抗生素类 抗肿瘤 抗HIV药 海绵相关真菌 

分 类 号：R914[医药卫生—药物化学]