海泥青霉Penicillium sp.WF-06的抗肿瘤活性代谢产物  

Antitumor Metabolites from Marine Sediment Derived Penicillium sp.WF-06

作　　者：任虹[1] 于洋[1] 

机构地区：[1]北京工商大学食品学院食品添加剂与配料北京高校工程研究中心,北京100048

出　　处：《国外医药（抗生素分册）》2011年第2期86-90,共5页World Notes on Antibiotics

基　　金：国家自然基金(30572279)资助

摘　　要：目的阐明海泥青霉Penicillium sp.WF-06的抗肿瘤活性次级代谢产物。方法 28℃下,130r/min摇床发酵7d培养生产菌WF-06,活性跟踪分离纯化WF-06发酵液中的活性单体化合物,根据理化性质和光谱分析(ESI MS、UV、IR、NMR等)鉴定单体化合物结构;采用细胞形态镜检、MTT方法评价单体化合物对人肝癌hepG2细胞的抗肿瘤活性。结果从青霉Penicillium sp.WF-06发酵液中分离并鉴定了6个生物碱类单体化合物,分别为四个环肽类化合物Gliocladine C(1)、环-甘氨酰脯氨酸(2)、环-苯丙氨酰脯氨酸(3)、环-色氨酰丙氨酸(4)和两个苯衍生物1,3-二氨基-2-硝基苯(5)和3-羧基吲哚(6),抗肿瘤活性检测结果发现化合物1对hepG2细胞显示增殖抑制活性,其IC50为19.6μmol/L,化合物2～6无活性(IC50>100μmol/L)。结论本实验首次评价了含硫环肽类化合物Gliocladine C对hepG2细胞的抗肿瘤活性,揭示了海泥青霉Penicillium sp.WF-06的主要抗肿瘤活性次级代谢物是含硫环肽类化合物。Objective To investigate the antitumor metabolites from marine sediment derived fungus Penicillium sp. WF-06. Methods The producing strain WF-06 was fermented in a rotary shaker at 28℃ and 130 r/min for 7 days and the bioactive metabolites in the fermentation broth were isolated through a bioassay-guided separation procedure. Structures of the bioactive compounds were determined on the basic of physicochemical and spectroscopic data. The antitumor activity against HepG2 cell line in vitro was assayed by MTT method, accompanied with the celt morphological observation under the light microscope. Results Six compounds were isolated from the fermentation broth of Penicillium sp. WF-06 and identified as four cyclopeptide derivatives including gliocladine C （1）, cycol-（Gly-Pro） （2）, cyclo - （Phe - Pro） （3）, cycol-（Trp-Ala） （4） and two benzene derivatives including 1,3- diamino- 2- nitrobenzene （5） and 1H-indole-3-carboxylic acid （6）. Compounds 1 - 6 inhibited the proliferation of HepG2 cells in various degrees, in which 1 inhibited the growth of HepG2 cells with the IC50 value of 19.6μmol/L, while compounds 2 - 6 have not shown significant cytotoxicity against HepG2 cells （IC50 〉 100 μmol/L）. Conclusions It is the first time to report the antitumor activity of gliocladin （1） on HepG2 cell line. The predominant antitumor metabolite from Penicillium sp. WF- 06 was sulphureous cyclo-peptide derivative.

关 键 词：PENICILLIUM sp.WF-06 活性跟踪 环肽类化合物 抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品]