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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 of the secondary metabolites of Aspergillus oryzae which are symbiotic with plant, and find out the compounds with good pharmacological activity. Methods: The crude extracts were separated and purified by normal-phase column chromatography, reversed-phase MPLC and HPLC. Three pure compounds were obtained by NMR techniques (1H-NMR, 13C-NMR, DEPT, HSQC, HMBC, COZY And NOESY) to determine their structure and to screen for their activity in inhibiting [beta] -secretase (BACE-I). RESULTS: Three compounds isolated from the secondary metabolites of Aspergillus oryzae were (1) (1S, 2S, 2’S, 6R, 8S, 8aR, 11R, 13R) -1,2,6,7,8, (2) (3’S) -3 ’, 8-hexahydro-11,13-dihydroxy-2,6- dimethyl-8- (2- methylbutyryl) oxy- (3) (1S, 2S, 2’S, 3’S, 6R, 8S, 8aR, 11R, 13R) - (1,2,6,7,8,8a-hexahydro-11,13- Methyl dihydroxy-2,6-dimethyl-8- (2-methyl-3-hydroxy-butyryl) oxy-1-naphthaleneheptanoate, which inhibit BACE-1 with IC50 of 18, 13 and 21μmol·L-1, respectively.Conclusion: The plant symbiotic Aspergillus oryzae secondary metabolites may have certain pharmacological effects against Alzheimer’s disease.