珊瑚共附生黄柄曲霉次级代谢产物研究
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摘要
目的研究东沙短足软珊瑚(Cladiella sp.)来源的黄柄曲霉菌(Aspergillus flavipes)中的活性次级代谢产物。方法采用硅胶柱层析、凝胶柱层析、制备HPLC等分离手段对真菌发酵液乙酸乙酯提取物进行分离,运用现代波谱技术结合文献报道数据,对化合物的结构进行鉴定;采用核因子κB受体活化因子配基(RANKL)诱导小鼠骨髓单核巨噬细胞(bone marrow macrophage cells,BMMs)分化为成熟的破骨细胞,经抗酒石酸酸性磷酸酶(TRAP)特异性染色,对化合物抑制破骨细胞分化活性进行研究。结果从该株真菌中分离得到4个细胞松弛素类化合物,其结构鉴定为trichalasins H,aspergilluchalasin,aspochalasin I和aspochalasin D。体外活性测试结果显示,化合物3和4可不同程度抑制BMMs向破骨细胞分化。结论对化合物3和4抑制破骨细胞分化活性的报告是本文首次报道,对新型抗骨质疏松活性物质研究具有科学价值。
Objective To investigate the active secondary metabolites of coral derived fungi Aspergillus flavipes.Methods Compounds were isolated and purified by means of various chromatographic techniques,including Silica gel column chromatography,Sephadex LH-20 chromatography and HPLC.The structure of the compounds was identified by NMR combined with the data reported.The nuclear factor kappa B receptor activating factor ligand(RANKL) was used to induce bone marrow macrophage cells(BMMs) differentiate into mature osteoclasts.The tartrate-resistant acid phosphatase(TRAP) specific staining was used to test the inhibitory activity of compounds on osteoclast differentiation.Results Four cytochalasins were isolated from the fungus and their structures were identified as trichalasins H,aspergilluchalasin,aspochalasin I and aspochalasin D.Compounds 3 and 4 showed inhibitory activity on osteoclast differentiation.Conclusion This was the first report of inhibiting osteoclast differentiation activity of compounds 3 and 4.These two compounds might have great significance in the study of new anti-osteoporosis drugs.
Objective To investigate the active secondary metabolites of coral derived fungi Aspergillus flavipes.Methods Compounds were isolated and purified by means of various chromatographic techniques,including Silica gel column chromatography,Sephadex LH-20 chromatography and HPLC.The structure of the compounds was identified by NMR combined with the data reported.The nuclear factor kappa B receptor activating factor ligand(RANKL) was used to induce bone marrow macrophage cells(BMMs) differentiate into mature osteoclasts.The tartrate-resistant acid phosphatase(TRAP) specific staining was used to test the inhibitory activity of compounds on osteoclast differentiation.Results Four cytochalasins were isolated from the fungus and their structures were identified as trichalasins H,aspergilluchalasin,aspochalasin I and aspochalasin D.Compounds 3 and 4 showed inhibitory activity on osteoclast differentiation.Conclusion This was the first report of inhibiting osteoclast differentiation activity of compounds 3 and 4.These two compounds might have great significance in the study of new anti-osteoporosis drugs.
引文
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[19] ZHAI Z J,LI H W,LIU G W,et al.Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo[J].Br J Pharmacol,2014,171(3):663-675.
[20] KIM J Y,CHEON Y H,KWAK S C,et al.Emodin regulates bone remodeling by inhibiting osteoclastogenesis and stimulating osteoblast formation[J].J Bone Miner Res,2014,29(7):1541-1553.
[2] ZHU W M,WANG J F.A review on studies of secondary metabolites from marine fungi[J].Mycosystema,2011,30 (2):218-228.
[3] 宋双,许佳怡.海洋来源的曲霉属真菌次级代谢产物及其活性研究进展[J].中山大学研究生学刊:自然科学与医学版,2015 (3):20-32.
[4] ROCHFORT S,FORD J,OVENDEN S,et al.A novel aspochalasin with HIV-1 integrase inhibitory activity from Aspergillus flavipes[J].J Antibiot,2005,58(4):279-283.
[5] ZHOU G X,WIJERATNE E M K,BIGELOW D,et al.Aspochalasins I,J,and K:Three new cytotoxic cytochalasans of Aspergillus flavipes from the Rhizosphere of Ericameria laricifolia of the Sonoran desert1 [J].J Nat Prod,2004,67(3):328-332.
[6] BARROW C J,SUN H H.Spiroquinazoline,a novel substance P inhibitor with a new carbon skeleton,isolated from Aspergillus flavipes[J].J Nat Prod,1994,57 (4):471-476.
[7] KWON YJ,MJ,CJ,et al.Flavimycins A and B,dimeric 1,3-dihydroisobenzofurans with peptide deformylase inhibitory activity from Aspergillus flavipes[J].J Nat Prod,2012,75(2):271-274.
[8] EL AMRANI M,LAI D,DEBBAB A,et al.Protein kinase and HDAC inhibitors from the endophytic fungus Epicoccum nigrum[J].J Nat Prod,2014,77(1):49-56.
[9] RUKACHAISIRIKUL V,RUNGSAIWATTANA N,KLAIKLAY S,et al.γ-Butyrolactone,cytochalasin,cyclic carbonate,eutypinic acid,and phenalenone derivatives from the soil fungus Aspergillus sp.PSU-RSPG185[J].J Nat Prod,2014,77(11):2375-2382.
[10] CHEN L,LIU Y T,SONG B,et al.Stereochemical determination of new cytochalasans from the plant endophytic fungus Trichoderma gamsii.[J].Fitoterapia,2014,96 (3):115-122.
[11] CHOO S J,YUN B S,RYOO I J,et al.Aspochalasin I,a melanogenesis inhibitor from Aspergillus sp.[J].J Microbiol Biotechnol,2009,19 (4):368-371.
[12] TOMIKAWA T,SHIN-YA K,KINOSHITA T,et al.Selective cytotoxicity and stereochemistry of aspochalasin D[J].J Antibiot,2001,54(4):379-381.
[13] ZHANG Y,WANG T,PEI Y,et al.Aspergillin PZ,a novel isoindole-alkaloid from Aspergillus awamori[J].J Antibiot,2002,55(8):693-695.
[14] IWAMOTO C,YAMADA T,ITO Y,et al.Cytotoxic cytochalasans from a Penicillium,species separated from a marine alga[J].Tetrahedron,2001,57 (15):2997-3004.
[15] QUANG D N,STADLER M,FOURNIER J,et al.Carneic acids A and B,chemotaxonomically significant antimicrobial agents from the xylariaceous ascomycete Hypoxylon carneum[J].J Nat Prod,2006,69 (8):1198-1202.
[16] ALVI K A,NAIR B,PU H,et al.Phomacins:Three novel antitumor cytochalasan constituents produced by a Phoma sp.[J].J Org Chem,1997,62(7):2148-2151.
[17] ZHANG Y,TIAN R,LIU S,et al.Alachalasins A–G,new cytochalasins from the fungus Stachybotrys charatum[J].Bioorg Med Chem,2009,16 (5):2627-2634.
[18] SI Y,TANG M,LIN S,et al.Cytotoxic cytochalasans from Aspergillus flavipes PJ03-11 by OSMAC method[J].Tetrahedron Letters,2018,59(18):1767-1771.
[19] ZHAI Z J,LI H W,LIU G W,et al.Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo[J].Br J Pharmacol,2014,171(3):663-675.
[20] KIM J Y,CHEON Y H,KWAK S C,et al.Emodin regulates bone remodeling by inhibiting osteoclastogenesis and stimulating osteoblast formation[J].J Bone Miner Res,2014,29(7):1541-1553.