黄芦木内生真菌Talaromyces tiftonensis SN34的次生代谢产物研究

Secondary metabolites of endophyties Talaromyces tiftonensis SN34 from Berberis amurensis

目的研究黄芦木叶片内生真菌Talaromyces tiftonensis SN34的次生代谢产物及生物活性。方法采用正相硅胶、SephadexLH-20凝胶、ODS等柱色谱和反相高效液相柱色谱对T.tiftonensisSN34的次生代谢物进行分离纯化,利用HRESIMS、NMR等谱学技术对化合物进行结构鉴定,并通过体外实验评价化合物抗菌、抗神经炎、细胞毒活性。结果从T.tiftonensis SN34的大米发酵物中分离得到7个化合物,分别鉴定为(2R)-4-甲氧基-2-羟基丙烷-6-甲基-2,3-二氢苯并呋喃-5-硫代甲酸酯(1)、(R)-4-羟基-2-羟基丙烷-6-甲基-2,3-二氢苯并呋喃-5-甲酸甲酯(2)、赤散囊菌素A(eurothiocin A,3)、2,3-二氢-2-(1-甲基乙烯基)-5-苯并呋喃甲醇(4)、意大利鼠李素(alaternin,5)、1,3,6-三羟基-7-(1-羟乙基)-9,10-蒽二酮(6)和BK223-B(7)。其中,化合物5对耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureu,MRSA)菌株的最小抑菌浓度为31.25μg/mL。20μmol/L的化合物3和5对脂多糖(lipopolysaccharides,LPS)诱导的BV2细胞产生一氧化氮(nitric oxide,NO)的抑制率分别为(69.90±1.34)%和(54.50±4.15)%。此外,化合物5和7可以抑制胰腺癌细胞PANC-1和BxPC的细胞增殖。结论化合物1为新型含硫苯并呋喃衍生物,命名为赤散囊菌素C;化合物2~7为首次从T.tiftonensis SN34中分离得到。化合物5对MRSA菌株具有一定的抑制作用。化合物3和5可以抑制LPS诱导的小鼠小胶质细胞系BV2细胞中NO的产生,具有一定的抗神经炎活性。此外,化合物5和7对PANC-1和Bx PC细胞增殖具有抑制作用。

Objective To study the secondary metabolites and biological activities of the endophyties Talaromyces.tiftonensis SN34 derived from the leaves of Berberis amurensis..Methods The secondary metabolites of T.tiftonensis SN34 were isolated and purified by normal-phase silica gel,Sephadex LH-20 gel,ODS column chromatography and reversed-phase high performance liquid column chromatography.The structures of isolated compounds were identified by HRESIMS and NMR.The antibacterial,antineuritis and cytotoxic activities of the compounds were evaluated by in vitro experiments.Results A total of seven compounds were isolated from the rice fermentation of T.tiftonensis SN34 and identified as S-methyl(R)-2-(2-hydroxypropan-2-yl)-4-methoxy-6-methyl-2,3-dihydrobenzofuran-5-carbothioate(1),methyl(R)-4-hydroxy-2-(2-hydroxypropan-2-yl)-6-methyl-2,3-dihydrobenzofuran-5-carboxylate(2),eurothiocin A(3),2,3-dihydro-2-(1-methylethenyl)-5-benzofuranmethanol(4),alaternin(5),1,3,6-trihydroxy-7-(1-hydroxyethyl)-9,10-anthracenedione(6),and BK223-B(7).Among them,compound 5 exhibited inhibition of methicillin-resistant Staphylococcus aureu(MRSA)bacterial strain,with a minimal inhibitory concentration(MIC)value of 31.25μg/mL.At a concentration of 20μmol/L,the inhibitory rates of compounds 3 and 5 on the production of nitric oxide(NO)in lipopolysaccharides(LPS)-induced mouse microglial cell line BV2 cells were(69.90±1.34)%and(54.50±4.15)%,respectively.In addition,compounds 5 and 7 could inhibit the proliferation of pancreatic cancer cell lines PANC-1 and BxPC.Conclusion Compound 1 is a novel sulfur-containing benzofuran derivative,which is named eurothiocin C.Compounds 2-7 are isolated from T.tiftonensis SN34 for the first time.Compound 5 has inhibitory effect on MRSA strains.Compounds 3 and 5 could inhibit NO production in the LPS-induced BV2 cells,suggesting that above compounds have antineuritis activity.In addition,compounds 5 and 7 exhibited inhibitory effects on the proliferation of PANC-1 and BxPC cells.