鄔氏黄丝曲霉产生的四个新组织蛋白酶抑制剂WortamannilactonesE-G.docVIP

邬氏黄丝曲霉产生的四个新组织蛋白酶抑制剂 Wortamannilactones E-G 董悦生1, 3 林洁2 路新华2 郑智慧2 马成伟1 刘梅2 白玉2张华2 杨峻山3 （1. 大连理工大学环境与生命学院生物科学与工程系 大连 116024； 2. 微生物国家工程中心，华北制药集团新药研发公司 石家庄 050015；3. 中国医学科学院-中国协和医科大学药用植物研究所，北京 100094） 摘要：目的 研究邬氏黄丝曲霉F01Z0195代谢产物中的抑制组织蛋白酶B的化学成份、生物活性并进行抑制剂和组织蛋白酶B的相互作用的分子模拟研究。方法：对邬氏黄丝曲霉F01Z0195进行发酵培养，对代谢产物进行分离纯化，使用现代光谱技术进行结构解析，并研究了其对组织蛋白酶B抑制活性及体内外毒性。结果 得到4个新化合物Wortamannilactones E-G，其对组织蛋白酶的抑制活性分别为4.3, 6.5, 13.0, and 6.0 ?mol/l。Wortamannilactones E对人正常细胞L-20细胞系在150 ?mol/l浓度下未显示毒性，其小鼠的急性毒性LD50为500mg/kg。结论 首次从土壤微生物代谢产物中分离得到了含有氧杂二环- [2.2.1]-庚烷和二氢吡喃环子结构的化合物；首次报道该类化合物具有组织蛋白酶B的抑制活性和较低的体内外毒性。 关键词：组织蛋白酶 B；抑制剂；邬氏黄丝曲霉；Wortamannilactones E-G Wortamannilactones E-G，four novel cathepsin B inhibitor from metabolites of the Fungus Talaromyces wortmannii DONG Yue-sheng1, Lin Jie2, Lu Xin-hua2, ZHENG Zhi-hui2, LIU Mei2, REN Xiao2, BAI Yu2, ZHANG hua2, YANG Jun-shan3 （1.Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, 116024; 2. National Microbial Medicine Engineering Research Center, New Drug RD Co. Ltd of North China Pharmaceutical Group Co. Ltd, Shijiazhuang 050015; 3. Institute of Medicinal Plant Development, China Academy of Medical Sciences Peking Union Medical College, Beijing 100094） Abstract: OBJCTIVE To study the chemical constituents from Talaromyces wortmannii and biological activity. METHODS The constituents were isolated and purified from the culture of Talaromyces wortmannii, their structure were determined by the spectroscopic analysis. The compound’s cathepsin B inhibitory activities, in vivo in vitro toxicities were also studied. RESULT Four novel compounds Wortamannilactones E-G were obtained and their IC50 values against cathepsin B were 4.3, 6.5, 13.0, and 6.0 ?mol/l, respectively. Wortamannilactones E showed no toxicity to human normal cell line L-20 at 150 uM, and its LD50 against mouse was 500mg/kg. COUCLUSION Compounds with oxabicyclo- [2.2.1] heptane and dihydropyran ring substructures were obtained from soil microorganism and