红榄李内生真菌Aspergillus terreus HT-1二酮哌嗪类次级代谢产物研究

Study on the diketopiperazines from the Lumnitzera littorea-derived fungus Aspergillus terreus HT-1

目的研究红榄李Lumnitzera littorea内生真菌Aspergillus terreus HT-1的次级代谢产物。方法对从红榄李中分离得到的内生真菌A.terreus HT-1进行大规模发酵,并采用多种色谱技术对其发酵产物进行分离纯化。通过多种波谱方法鉴定单体化合物结构。结果从A.terreus HT-1发酵产物的乙酸乙酯萃取物中分离得到了15个二酮哌嗪类化合物,分别鉴定为bis(dethio)bis(methylsulfanyl)gliotoxin(1),环(D-4-羟基-脯氨酸-L-苯丙氨酸)二肽(2),环(L-4-羟基-脯氨酸-L-苯丙氨酸)二肽(3),环(L-4-羟基-脯氨酸-L-酪氨酸)二肽(4),环(L-4-羟基-脯氨酸-L-亮氨酸)二肽(5),环(L-丙氨酸-L-4-羟基-脯氨酸)二肽(6),环(D-4-羟基-脯氨酸-D-异亮氨酸)二肽(7),环(D-脯氨酸-L-酪氨酸)二肽(8),环(L-亮氨酸-L-脯氨酸)二肽(9),环(L-脯氨酸-L-苏氨酸)二肽(10),环(L-脯氨酸-L-丙氨酸)二肽(11),环(L-脯氨酸-甘氨酸)二肽(12),环(L-苯丙氨酸-甘氨酸)二肽(13),环(谷氨酸-L-酪氨酸)二肽(14),terezine D(15),并采用MTT法检测全部化合物的神经保护活性。结论在200μmol/L浓度下,化合物1和5显示出较好的神经保护活性,使H2O2诱导氧化损伤的神经细胞(HT22)的细胞存活率从44.06%分别提高到69.51%和76.75%。本研究为红榄李及其内生真菌的开发利用研究提供了理论基础。

Objective To study the secondary metabolites of Aspergillus terreus HT-1,an endophytic fungus from Lumnitzera littorea.Methods The endophytic fungus A.terreus HT-1 was isolated from a mangrove plant,L.littorea.Its secondary metabolites were puri?ed by various chromatograph technology,and the structures of the isolated compounds were identi?ed on the basis of spectral evidences.Results Fifteen diketopiperazines,bis(dethio)bis(methylsulfanyl)gliotoxin(1),cyclo-(D-4-OH-Pro-L-Phe)(2),cyclo-(L-4-OH-Pro-L-Phe)(3),cyclo-(L-4-OH-Pro-L-Tyr)(4),cyclo-(L-4-OH-Pro-L-Leu)(5),cyclo-(L-Ala-L-4-OH-Pro)(6),cyclo-(D-4-OH-Pro-D-Ile)(7),cyclo-(D-Pro-L-Tyr)(8),cyclo-(L-Leu-L-Pro)(9),cyclo-(L-Pro-L-Thr)(10),cyclo-(L-Pro-L-Ala)(11),cyclo-(L-Pro-Gly)(12),cyclo-(L-Phe-Gly)(13),cyclo-(Glu-L-Tyr)(14),and terezine D(15)were isolated from the EtOAc extract of the secondary metabolites of A.terreus HT-1.The neuroprotective activities of all compounds were detected by MTT method.Conclusion At a concentration of 200μmol/L,compounds 1and 5 showed obvious neuroprotective activity,increased the cell survival rate of H2O2induced oxidative damage HT22 cells from 44.06%to 69.51%and 76.75%,respectively.This study provides a theoretical basis for the development and utilization of mangrove plant and its endophytic fungi.