内生真菌Paraconiothyrium brasiliense代谢产物β-咔啉生物碱及其黄嘌呤氧化酶抑制活性研究

Study onβ-carboline alkaloids produced by endophytic fungus Paraconiothyrium brasiliense and their xanthine oxidase inhibitory activity

本研究通过前体介导调控一株内生真菌的次级代谢产物,采用正相硅胶柱色谱和制备型HPLC等方法分离纯化,利用NMR、MS等波谱学方法鉴定化合物结构,从中分离鉴定了10个生物碱类化合物,鉴定结果为:川芎哚(1)、1-(1′,2′-二脱氧-α-D-核吡喃糖基)-β-咔啉(2)、flazin(3)、tangutorid E(4)、1-乙酰基-β-咔啉(5)、4-(9H-β-carbolin-1-yl)-4-oxobutyric acid(6)、1-(furan-2-yl)-9H-pyrido[3,4-b]indole(7)、indole-3-ethanol(8)、indole-3-acetic acid(9)和indole-3-carboxaldehyde(10)。化合物1~10均为首次从该属菌株中分离得到,其中7个β-咔啉生物碱;对10个生物碱进行了黄嘌呤氧化酶抑制活性测试,结果显示7个化合物具有明显的抑制活性,IC50值的范围在0.68~9.30 mM之间,且化合物2、3和6的抑制活性优于阳性药。

In this study,the secondary metabolites of an endophytic fungus were regulated by precursor mediated regulation.To study the secondary metabolites,various chromatographic techniques,including normal phase silica gel column chromatography and preparative HPLC were used.Their structures were determined by various spectroscopic data,such as NMR and MS.Finally,10 alkaloids were isolated from P.brasiliense and their structures were identified as perlolyrine(1),1-(1′,2′-dideoxy-α-D-nucleopyranosyl)-β-carbamate porphyrin(2),flazin(3),tangutorid E(4),1-acetyl-β-carboline(5),4-(9H-β-carbolin-1-yl)-4-oxobutyric acid(6),1-(furan-2-yl)-9H-pyrido[3,4-b]indole(7),indole-3-ethanol(8),indole-3-acetic acid(9),and indole-3-carboxaldehyde(10).All the 10 alkaloids were isolated from this genus of Paraconiothyrium sp.for the first time.Among them,7 compounds wereβ-carboline alkaloids.In addition,the xanthine oxidase inhibitory activity was tested for compounds 1-10.The results showed that 7 compounds had significant inhibitory activity,and the IC50 value ranged from 0.68 to 9.30 mM.It was worth noting that the inhibitory activities of compounds 2,3 and 6 were better than that of positive drug.