微生物来源的胆固醇生物合成酶抑制剂.Ⅸ.抗生素SIPI-8917-Ⅳ的研究

Enzyme inhibitor of cholesterol biosynthetic enzyme from microorganisms. Ⅸ. studies on antibiotic SIPI 8917 Ⅳ

本实验室建立胆固醇生物合成的体外酶反应测试方法，应用其筛选真菌产生的具有抑制胆固醇生物合成活性的发酵样品，其中ＳＩＰＩ－８９１７菌株代谢产物表现出抑制活性；对其代谢产物进行研究，应用丙酮浸泡、溶媒萃取、硅胶柱分离、ＬＨ２０凝胶层析和重结晶等方法，从其菌丝体中分离出活性成分ＳＩＰＩ－８９１７－Ⅳ。通过元素分析和质谱（ＥＩ和ＨＲＭＳ），确定其分子式为：Ｃ１９Ｈ１４Ｏ７（分子量３５４．０７８７）。综合紫外光谱、红外光谱、１Ｈ－ＮＭＲ和１３Ｃ－ＮＭＲ等图谱数据的解析，确定ＳＩＰＩ－８９１７－Ⅳ的结构与６－甲氧基柄曲菌素（６－ｍｅｔｈｏｘｙｓ－ｔｅｒｉｇｍａｔｏｃｙｓｔｉｎ）一致。生物活性研究表明，其具有抑制胆固醇生物合成活性，文献报道其具有抑制细胞线粒体呼吸作用，并与ＤＮＡ相互作用，其他活性有待进一步研究。

Assay method of cholesterol biosynthesis in a enzyme system in vitro has been set up at our laboratory. Using this method, we screened the fermentation broths of fungi collected in our laboratory, a positive strain named SIPI 8917 exhibited inhibitory activities on cholesterol biosynthetic enzyme. Physiologically active compound SIPI 8917 Ⅳ was isolated from fungus SIPI 8917 by acetone soaking, solvent extraction, silica gel column, LH20 column chromatography and recrystallization etc.. By elemental analysis and MS (EI and HRMS), its formula was determined to be C 19 H 14 O 7 (MW: 354.0787); based on the UV, IR, 1H NMR, 13 C NMR etc. spectral data and physicol chemical properties of SIPI 8917 Ⅳ, the structure of SIPI 8926 Ⅳ was elucidated and was identical with that of 6 methoxysterigmatocystin. It showed inhibitory activities on cholesterol biosynthesis in a enzyme system in vitro.