湖北旋覆花化学成分及抗结核活性研究
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摘要
为进一步研究湖北旋覆花花序中的化学成分及抗结核活性。实验采用硅胶柱色谱、反相硅胶柱色谱以及制备型高相液相等方法进行了成分系统研究,肉汤二倍稀释法测定化合物的体外抗结核分支杆菌活性。从其花序中分离得到10个化合物。应用波谱学方法分别鉴定为:7,8-epoxy-9-(isobutyryloxy)thymolisobutyrate(1)、10-(2-methylbutyloxy)-8,9-epoxythymolisobutyrate(2)、stigmasterol(3)、ayapin(4)、ergolide(5)、5,10-epi-2,3-dihydroaromatin(6)、xanthalongin(7)、bigelovin(8)、carpesiolin(9)、aromaticin(10)。化合物1、2、5、6、8～10均为首次从该植物中分离得到。其中化合物5～10均为倍半萜类化合物。化合物5、6、8～10对结核分枝杆菌细胞株具有较好的抑制活性,最小抑制浓度MIC值分别为10.00、30.00、5.00、3.15、3.15μM,9和10的活性效果显著。
To investigate chemical constituents and anti-tuberculosis activity in vitro from the flowers of Inula hupehensis Ling,various chromatographic techniques,including silica gel column chromatography,ODS and preparative HPLC were used.Anti-tuberculosis activity in vitro was determined by double broth dilution method.Ten compounds were isolated.Their structures were identified on the basis of NMR,MS as 7,8-epoxy-9-(isobutyryloxy)thymolisobutyrate(1),10-(2-methylbutyloxy)-8,9-epoxythymolisobutyrate(2),stigmasterol(3),ayapin(4),ergolide(5),5,10-epi-2,3-dihydroaromatin(6),xanthalongin(7),bigelovin(8),carpesiolin(9),aromaticin(10).Compounds 1,2,5,6,8-10 were isolated from this plant for the first time.Compounds 5-10 are sesquiterpenoids.Compounds 5,6,8-10 have coninhibitory activity against mycobacterium tuberculosis cell lines.Minimal inhibition concentration MIC as follows:10.00,30.00,5.00,3.15,3.15 μM.
To investigate chemical constituents and anti-tuberculosis activity in vitro from the flowers of Inula hupehensis Ling,various chromatographic techniques,including silica gel column chromatography,ODS and preparative HPLC were used.Anti-tuberculosis activity in vitro was determined by double broth dilution method.Ten compounds were isolated.Their structures were identified on the basis of NMR,MS as 7,8-epoxy-9-(isobutyryloxy)thymolisobutyrate(1),10-(2-methylbutyloxy)-8,9-epoxythymolisobutyrate(2),stigmasterol(3),ayapin(4),ergolide(5),5,10-epi-2,3-dihydroaromatin(6),xanthalongin(7),bigelovin(8),carpesiolin(9),aromaticin(10).Compounds 1,2,5,6,8-10 were isolated from this plant for the first time.Compounds 5-10 are sesquiterpenoids.Compounds 5,6,8-10 have coninhibitory activity against mycobacterium tuberculosis cell lines.Minimal inhibition concentration MIC as follows:10.00,30.00,5.00,3.15,3.15 μM.
引文
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14 Jerezano A,Jiménez F,Delgado F,et al.New approach for the construction of the Coumarin Frame and application in the total synthesis of natural products[J].Arch Pharm Res,2011,42:185-198.
15 Huang HQ,Piao XL,Yan MN,et al.Seven sesquiterpene lactones from flower of Inula helianthus-aquatica[J].Chin J Exp Tradit Med From(中国实验方剂学杂志),2011,17:112-115.
16 Merfort I,Wendisch D.Sesquiterpene lactones of Arnica cordifolia,subgenus Austromontana[J].Phytochemistry,1993,34:1436-1437.
17 Willuhn G,Skibinski A,Schmidt TJ.Structure revision of xanthalongin and further sesquiterpene lactones from flowers of Arnica longifolia[J].Planta Med,1998,64:635-639.
18 Wang Q,Zhou BN,Zhang RW,et al.Cytotoxicity and NMR spectral assignments of ergolide and bigelovin[J].Planta Med,1996,62:166-168.
19 Maruyama M,Omura S.Carpesiolin from Carpesium abrotanoides[J].Phytochemistry,1977,16:782-783.
20 Majetich G,Song JS,Leigh AJ,et al.Allylsilane-based annulations.Direct stereoselective syntheses of(±)-graveolide and(±)-aromaticin[J].Nat Prod Lett,1993,1:179-186.
2 Marco JA,Sanz-Cervera JF,Manglano E.Chlorinated thymol derivatives from Inula crithmoides[J].Phytochemistry,1993,33:875-878.
3 Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China:Vol Ⅰ(中华人民共和国药典:第一部)[M].Beijing:China Medical Science Press,2010.
4 Wu YB,Zhang DQ,Wang YZ.Advances in the study of chemical constituents of Inula britannica[J].Nat Prod Res Dev(天然产物研究与开发),2006,18:503-507.
5 GUO QL,Yang JS.Sesquiterpenes in Inula L.plants and their pharmacological activities[J].Nat Prod Res Dev(天然产物研究与开发),2005,17:804-809.
6 Zhang XY,Wang ZX,Shan JJ.Constituents and phamacological activities of Inula L.[J].Int Pharm Res(国际药学研究杂志),2008,35:433-440.
7 Qin JJ.The discovery and biological activities evalution of novel sesquiterpenes and from four medicinal plants of the Genus Inula[D].Shanghai:Shanghai Jiao Tong University(上海交通大学),2011.
8 Cheng XR.Studies on bioactive secondary metabolites from four medicinal plants of Genus Inula[D].Shanghai:Shanghai Jiao Tong University(上海交通大学),2012.
9 Ma AJ,Zhao YL.The prevalence and surveillance of drug-resistant tuberculosis[J].Chin J Antibiot(中国抗生素杂志),2018,43:502-506.
10 Fan JW,Yu L,Ma LZ,et al.Antimycobacterial activity of 29 plants extracts[J].Chin Sci Bull(中国农学通报),2009,25(24):1-7.
11 Mossa JS,El-Feraly FS,Muhammad I,et al.Sesquiterpene lactones and thymol esters from Vicoa pentanema[J].J Nat Prod(天然产物杂志),1997,60:550-555.
12 Zee OP,Kim DK,Kang RL.Thymol derivatives from Carpesium divaricatum[J].Arch Pharm Res,1998,21:618-620.
13 Zhang XQ,Qi J,Ye WC.Chemical constituents of Xanthium sibiricum Patr.ex Widder.[J].Chin Pharm Univ(中国药科大学学报),2004,35:404-405.
14 Jerezano A,Jiménez F,Delgado F,et al.New approach for the construction of the Coumarin Frame and application in the total synthesis of natural products[J].Arch Pharm Res,2011,42:185-198.
15 Huang HQ,Piao XL,Yan MN,et al.Seven sesquiterpene lactones from flower of Inula helianthus-aquatica[J].Chin J Exp Tradit Med From(中国实验方剂学杂志),2011,17:112-115.
16 Merfort I,Wendisch D.Sesquiterpene lactones of Arnica cordifolia,subgenus Austromontana[J].Phytochemistry,1993,34:1436-1437.
17 Willuhn G,Skibinski A,Schmidt TJ.Structure revision of xanthalongin and further sesquiterpene lactones from flowers of Arnica longifolia[J].Planta Med,1998,64:635-639.
18 Wang Q,Zhou BN,Zhang RW,et al.Cytotoxicity and NMR spectral assignments of ergolide and bigelovin[J].Planta Med,1996,62:166-168.
19 Maruyama M,Omura S.Carpesiolin from Carpesium abrotanoides[J].Phytochemistry,1977,16:782-783.
20 Majetich G,Song JS,Leigh AJ,et al.Allylsilane-based annulations.Direct stereoselective syntheses of(±)-graveolide and(±)-aromaticin[J].Nat Prod Lett,1993,1:179-186.