米曲霉三种化学成分及其抗阿尔茨海默病活性的研究

Study on three chemical constituents of Aspergillus niger and its anti Alzheimer disease activity

目的:对植物共生的米曲霉次生代谢产物的化学成分进行分析,寻找其中药理活性好的化合物。方法:采用正相柱层析、反相MPLC、HPLC等分离手段对原浸膏进行分离纯化,得到3个纯化合物,通过NMR技术(1H-NMR、13C-NMR、DEPT、HSQC、HMBC、COSY和NOESY)确定它们的结构,并对它们抑制β-分泌酶(BACE-1)的活性进行筛选。结果:从米曲霉次生代谢产物中分离得到的3个化合物,分别为(1)(1S,2S,2'S,6R,8S,8aR,11R,13R)-1,2,6,7,8,8A-六氢化-11,13-二羟基-2,6-二甲基-8-(2-甲基丁酰)氧基-1-萘庚酸甲酯;(2)(3'S)-3'-羟基-洛伐他汀;(3)(1S,2S,2'S,3'S,6R,8S,8aR,11R,13R)-(1,2,6,7,8,8a-六氢化-11,13-二羟基-2,6-二甲基-8-(2-甲基-3-羟基-丁酰)氧基-1-萘庚酸甲酯,它们对BACE-1有抑制作用,其IC50分别是18、13和21μmol·L-1。结论:植物共生的米曲霉次生代谢产物对抗阿尔茨海默病可能具有一定的药理作用。

Objective： To analyze the chemical constituents from endophytic fungi secondary metabolites of Aspergillus oryzae,and to explore the great pharmacological compounds. Method： Silica gel column chromatography,ODS column chromatography,HPLC were used to isolate compounds from the fungi,and three purified compounds were got. On the basis of NMR spectral（1H-NMR,13C-NMR,DEPT,HSQC,HMBC,COSY,NOESY）,the chemical constituent was confirmed and the inhabit BACE-1 activity was measured to screen. Results： Three compounts were isolated from the Aspergillus oryzae. They were（ 1）（ 1S,2S,2’S,6R,8S,8aR,11 R,13R）-（ 1,2,6,7,8,8A-Hexahydro-11,13-dihydroxy-2,6-dimethyl-8-（ 2-methylbutyryl） oxy-1-naphthalene heptanoic acid methyl ester,（ 2）（ 3’S）-3’-Hydroxy-lovastatin,（ 3）（ 1S,2S,2’S,3’S,6R,8S,8aR,11 R,13R）-（ 1,2,6,7,8,8a Hexahydro-11,13-dihydroxy-2,6-dimethyl-8-（ 2-methyl-3-hydroxybutyryl） oxy-1-naphthalene heptanoic acid methyl ester. All of the three compounds were be found to have the inhabit BACE-1 activity with the IC50 value of 18,13,21 μmol ·L-1,respectively. Conclusion： The secondary metabolites produced by Aspergillus oryzae of Plant symbiosis maybe have some certain pharmacological action on the Alzheimer disease treatment.