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湖北贝母内生真菌Boeremia exigua化学成分及其抗炎活性研究

2022-03-10吕晓叶可马旭军吴凯玥黄蓉艾洪莲

关键词:抗炎组分液相

吕晓,叶可,马旭军,吴凯玥,黄蓉,艾洪莲

(中南民族大学 药学院,武汉 430074)

植物内生真菌作为重要的与植物互作微生物类群,在与植物长期的协同进化过程中形成了特殊的互惠共生关系,具有极高的生物多样性[1].从内生真菌中分离得到的有生物活性天然产物数量和种类比任意其他微生物都多[2-3].这促使内生真菌成为了寻找活性成分的潜在资源,为植物资源的保护提供了思路[4-5].湖北贝母(Fritillaria hupehensisHsiao et K.C.Hsia),是百合科贝母属草本植物,其干燥鳞茎入药. 微苦,性寒. 归肺、心经[6]. 用于热痰咳嗽,痰核瘰疬,痈肿疮毒. 本文以一株优势内生真菌菌株Boeremia exigua为研究对象,对其固体发酵物的次生代谢产物进行研究.分离纯化得到了9个单体化合物(图1),均为细胞松弛素类化合物.进一步的抗炎活性检测显示,与阳性药PDTC相比,化合物1、2和3有着较好的抗炎活性,IC50分别为8.42、22.05和6.26μM, 为该类真菌抗炎药物的研发提供了物质基础.

图1 化合物1~9的结构Fig.1 Chemical structures of compounds 1-9

1 实验部分

1.1 实验仪器与材料

核磁共振波谱仪(AM600,德国Bruker).旋转蒸发仪(SB-1300,ELELA),中压液相色谱(puriflash 430,法国Interchim)制备、半制备高效液相色谱(1260型,美国Agilent),酶标仪(瑞士TECAN).

正相柱色谱硅胶(80~100 目和200~300 目)和GF254薄层色谱板(青岛海洋化工厂);Sephadex LH-20凝胶材料(瑞典Amersham Bioscience);反相柱色谱材料Chromatorex(40~75μm)(日本富士);色谱柱为Agilent Zorbax SB-18(4.6 mm×150 mm,5μm)和Agilent Zorbax SB-C18 柱(9.4 mm×150 mm,5μm).显色方法为紫外灯下波长254 nm和365 nm处观察荧光,香草醛显色及10%硫酸乙醇溶液显色剂加热显色.

1.2 菌种分离纯化及发酵培养

该内生真菌分离自贝母新鲜植株的根部,贝母采自湖北省恩施州恩施市新塘乡双河社区,菌株自编号为贝21.通过ITS序列测定结果对比得知,该序列与Boeremia exigua的最大相似度达100%.基因库登录号为MT154621.1.故将其鉴定为Boeremia exigua.该菌株保藏于中南民族大学药学院微生物菌种库.

其具体分离过程为:贝母新鲜块根自来水冲洗干净后切成小段,75%乙醇润洗60 s,无菌水漂洗3 次. 0.1%升汞浸泡消毒40 s,无菌水漂洗3 次.吸干水分,剪去贝母根部两端的切口后从中划开.将这些小块接至PDA培养基(含青链霉素混合液)中,置于25 ℃的恒温培养箱培养.待真菌长出后,挑取菌丝进行纯化培养得单一菌株.

本研究采用大米固体发酵培养. 培养基:每瓶大米50 g,加水50 mL,共340瓶,置于500 mL培养瓶中经120 ℃高温灭菌.培养条件:25 ℃下暗培养30 d.

1.3 提取分离

将发酵后的固体培养基用甲醇浸泡3 次,每次6 h.合并提取液,减压浓缩蒸干有机试剂后,用水溶解,并用乙酸乙酯萃取3次,将乙酸乙酯部分合并浓缩得到粗浸膏900 g.浸膏经正相硅胶柱层析(四氟层析柱,100 mm ×1000 mm,氯仿-甲醇:100∶0 →0∶100)梯度洗脱得到6 个组分(A~E). 组分B 经中压液相色谱(色谱柱型号:YMC-Pack ODS-A,S-5 μm,12 nm,AA12S05-2510 WT,水-甲醇:80∶20 →0∶100)分离,得到4 个亚组分B1~B4.B2 中有结晶析出,清洗后得到化合物1.将晶体母液经制备型高效液相色谱分离(色谱柱型号:YMC-Pack ODS-A,S-5 μm,12 nm,AA12S05-1510 WT,水-乙腈80 ∶20 →0∶100)得到化合物2. B3 经正相硅胶柱层析(四氟层析柱,石油醚-丙酮80∶20 →0∶100)分离得到5 个组分(B3-1~B3-5).B3-3 再经制备行高效液相色谱分离纯化得到化合物4. B3-5 经凝胶柱色谱分离得到8 个组分(B3-5a~B3-5h). B3-5h 经高效液相色谱(色谱柱型号:YMC-Pack ODS-A,S-5 μm,12 nm,AA12S05-1510 WT,水-乙腈80∶20 →0∶100)分离纯化,得到化合物3 和5.组分C 经中压液相色谱(色谱柱型号:YMC-Pack ODS-A,S-5 μm,12 nm,AA12S05-2510 WT,水-甲醇:80∶20 →0∶100)分离得到6 个亚组分(C1~C-6).C2 经正相硅胶柱层析(四氟层析柱,氯仿-甲醇80∶20 →0∶100)得到7个组分(C2-1~C2-7),C2-6和C2-7经制备型高效液相色谱(色谱柱型号:YMC-Pack ODS-A,S-5 μm,12 nm,AA12S05-1510 WT,水-乙腈80∶20 →0∶100)分离纯化,得到化合物6、7、8和9.

2 抗炎活性检测

采用Lipopolysaccharide(LPS)诱导的RAW 264.7 巨噬细胞产生NO 的炎症效应来检测化合物1~9 的抗炎活性. 在含10%胎牛血清、100 U/mL 青霉素和100 g/mL 链霉素的dulbecco′s modified eagle medium(DMEM)培养基于恒温培养箱中传代培养(5%CO2,37 ℃).将RAW 264.7 细胞(5×105细胞/mL)接种到96孔多孔板中培养12 h后,用不同浓度的测试化合物(10~40 mM)处理2 h,然后在有无脂多糖(500 ng/mL)的情况下孵育24 h.除去培养基,在每孔中加入100 μmol/mL 3-(4,5)-dimethylthiahiazo(-zy1)-3,5-di- phenytetrazoliumromide(MTT) 溶 液(0.5 mg/mL),随后在37 ℃下培养4 h,每个孔用150 μL DMSO 溶解晶体.酶标仪570 nm 处测吸光度,细胞存活率为对照的百分比来表示.使用Griess 试剂盒收集细胞上清液,以测量上清液中NO 的产生.使用酶标仪在540 nm处测量吸光度.阳性对照药为Pyrrolidinedithiocarbamate(简称PDTC).

3 结构鉴定

化合物1:分子式为C29H37NO5,白色粉末.1H NMR(CD3OD,600 MHz):δH7.27(2H,t,J= 7.4 Hz,H-3′,5′),7.19(1H,t,J=7.4 Hz,H-4′),7.14(2H,d,J=7.4 Hz,H-2′,6′),6.93(1H,dd,J=15.7,4.4 Hz,H-21),5.83(1H,ddd,J=15.0,9.9,1.6 Hz,H-13),5.78(1H,dd,J=15.7,1.8,H-22),5.29(H1,s,H-12a),5.24(1H,m,H-14),5.09(1H,s,H-12b),4.45(1H,m,H-20),3.80(1H,d,J= 11.0 Hz,H-7),3.39(1H,m,H-8),3.37(1H,m,H-3),3.21(1H,m,H-5),2.85(1H,dd,J=5.3,2.7 Hz,H-4),2.80(2H,m,H-10),2.09(1H,m,H-19a),1.91(1H,m,H-15a),1.72(1H,m,H-17a),1.66(1H,m,H-19b),1.56(1H,m,H-15b),1.45(1H,m,H-18a),1.28(1H,m,H-18b),1.22(1H,m,H-16),0.88(3H,d,J =6.6 Hz,H-24),0.86(3H,d,J =6.8 Hz,H-11),0.58(1H,m,H-17b).13C NMR(CD3OD,150 MHz):δc174.0(C-1),166.4(C-23),154.7(C-21),151.5(C-6),138.3(C-1′),136.7(C-14),131.0(C-6′),131.0(C-2′),129.6(C-3′),129.6(C-5′),128.7(C-13),127.9(C-4′),119.5(C-22),114.3(C-12),85.4(C-9),71.5(C-7),71.1(C-20),54.8(C-3),49.4(C-8),49.0(C-4),44.0(C-10),43.2(C-19),36.6(C-17),35.4(C-15),34.5(C-16),32.8(C-5),21.5(C-18),20.7(C-24),14.1(C-11).以上数据与文献[7]数据基本一致,故化合物1被确定为Cytochalasin B.

化合物2:分子式为C29H37NO5,白色粉末.1H NMR(CD3OD,600 MHz):δH7.31(2H,t,J =7.6 Hz,H-3′,5′),7.23(1H,m,H-4′),7.14(1H,m,H-21),7.12(2H,m,H-2′,6′),6.10(1H,ddd,J =15.2,10.1,1.8 Hz,H-13),5.97(1H,dd,J =15.7,2.0 Hz,H-22),5.22(1H,m,H-14),4.57(1H,m,H-20),3.87(1H,m,H-7),3.56(1H,s,H-4),3.51(1H,dd,J =9.9,5.3 Hz,H-3),3.24(1H,t,J=10.1,H-8),3.00(1H,dd,J=13.0,5.3 Hz,H-10a),2.69(1H,dd,J =13.0,9.9 Hz,H-10b),2.08(1H,m,H-15a),1.96(1H,m,H-19a),1.74(1H,m,H-17a),1.67(1H,m,H-15b),1.63(3H,s,H-12),1.58(1H,m,H-19b),1.58(2H,m,H-18),1.28(3H,s,H-11),1.27(1H,m,H-16),0.89(3H,d,J =6.7 Hz,H-24),0.59(1H,m,H-17b).13C NMR(CD3OD,150 MHz):δc174.6(C-1),166.4(C-23),155.3(C-21),138.8(C-1′),136.4(C-14),135.1(C-6),131.0(C-2′),131.0(C-6′),129.8(C-3′),129.8(C-5′),129.2(C-13),127.9(C-4′),126.7(C-5),119.5(C-22),85.8(C-9),71.7(C-7),70.6(C-20),60.6(C-3),50.4(C-8),44.1(C-10),43.5(C-15),36.9(C-17),35.3(C-19),34.7(C-16),21.3(C-18),20.8(C-24),17.6(C-11),14.7(C-12).以上数据与文献[8]数据基本一致,故化合物2被确定为Cytochalasin B2.

化合物3:分子式为C29H37NO5,无色油状.1H NMR(CDCl3,600 MHz):δH7.33(2H,t,J =7.5 Hz,H-3′,5′),7.26(1H,m,H-4′),7.14(2H,m,H-2′,6′),7.04(1H,dd,J =15.7,3.9 Hz,H-21),6.08(1H,ddd,J=15.1,10.0,1.9 Hz,H-13),5.93(1H,dd,J =15.7,2.0 Hz,H-22),5.30(1H,ddd,J =15.1,10.9,3.7 Hz,H-14),4.54(1H,s,H-20),3.68(1H,t,J=7.1 Hz,H-3),3.13(1H,dd,J=10.0,5.4 Hz,H-8),2.85(1H,d,J=5.8 Hz,H-4),2.78-2.80(2H,m,H-10),2.74(1H,d,J =5.4 Hz,H-7),2.33(1H,m,H-5),2.08(1H,m,H-15a),1.93(1H,m,H-19a),1.72(1H,m,H-15b),1.63(1H,m,H-19b),1.62(1H,m,H-17a),1.49(1H,m,H-18a),1.24(1H,m,H-18b),1.23(3H,s,H-12),1.22(1H,m,H-16),1.01(3H,d,J =7.2 Hz,H-11),0.87(3H,d,J=6.6 Hz,H-24),0.65(1H,m,H-17b).13C NMR(CDCl3,150 MHz):δc172.6(C-1),164.7(C-23),152.6(C-21),137.0(C-1′),136.0(C-14),129.4(C-2′),129.4(C-6′),129.1(C-3′),129.1(C-5′),127.3(C-4′),126.5(C-13),118.8(C-22),84.6(C-9),70.5(C-20),61.1(C-7),57.5(C-6),54.0(C-3),49.2(C-4),46.1(C-8),45.2(C-10),41.9(C-15),36.1(C-5),35.4(C-17),34.8(C-19),33.2(C-16),20.5(C-24),20.2(C-18),19.7(C-12),12.9(C-11).以上数据与文献[9]数据基本一致,故化合物3被确定为Cytochalasin F.

化合物4:分子式为C29H37NO5,白色粉末.1H NMR(CD3OD,600 MHz):δH7.27(2H,d,J =7.5 Hz,H-3′,5′),7.19(3H,m,H-2′,4′,6′),6.99(1H,dd,J =15.6,5.7 Hz,H-21),5.91(1H,ddd,J =15.0,10.2,2.0 Hz,H-13),5.78(1H,dd,J =15.6,1.6 Hz,H-22),5.57(1H,m,H-7),5.26(1H,ddd,J =15.0,10.8,3.1 Hz,H-14),4.39(1H,m,H-20),4.07(2H,br s,H-12),3.45(1H,m,H-3),3.42(1H,m,H-8),2.95(1H,m,H-5),2.88(2H,m,H-10),2.75(1H,t,J=4.4 Hz,H-4),2.11(1H,m,H-15a),1.89(1H,m,H-19a),1.75(1H,m,H-17a),1.69(1H,m,H-15b),1.58(1H,m,H-19b),1.44(1H,m,H-18a),1.37(1H,m,H-18b),1.31(1H,m,H-16),1.09(3H,d,J=7.3 Hz,H-11),0.89(3H,d,J =6.6 Hz,H-24),0.62(1H,m,17b).13C NMR (CD3OD,150 MHz):δc174.2(C-1),166.5(C-23),154.3(C-21),145.1(C-6),138.6(C-1′),135.6(C-14),131.0(C-2′),131.0(C-6′),129.6(C-3′),129.6(C-5′),129.6(C-13),127.8(C-4′),126.7(C-7),120.0(C-22),88.6(C-9),71.7(C-20),63.3(C-12),57.2(C-3),51.0(C-4),46.6(C-8),44.2(C-10),42.6(C-15),36.2(C-17),35.5(C-19),35.0(C-16),34.4(C-5),21.6(C-18),20.7(C-24),13.1(C-11).以上数据与文献[10]数据基本一致,故化合物4被确定为Cytochalasin Z2.

化合物5:分子式为C29H37NO4,白色粉末.1H NMR(CDCl3,600 MHz):δH7.32(2H,t,J=7.5 Hz,H-3′,5′),7.26(1H,m,H-4′),7.19(2H,d,J =7.5 Hz,H-2′,6′),7.07(1H,dd,J =15.6,6.4 Hz,H-21),5.91(1H,m,H-13),5.88(1H,m,H-22),5.51(1H,m,H-7),5.30(1H,ddd,J =14.4,10.7,3.1 Hz,H-14),4.45(1H,m,H-20),3.32(1H,d,J =10.1 Hz,H-3),3.13(1H,m,H-4),2.92(1H,m,H-5),2.89(2H,m,H-10),2.74(1H,t,J=3.1,H-8),2.11(1H,m,H-15a),1.89(1H,m,H-19a),1.77(3H,s,H-12),1.76(1H,m,H-17a),1.68(1H,m,H-15b),1.58(1H,m,H-19b),1.47(1H,m,H-15b),1.38(2H,m,H-18),1.25(1H,m,H-16),1.23(3H,d,J =7.3 Hz,H-11),0.88(3H,d,J=6.6 Hz,H-24),0.72(1H,m,H-17b).13C NMR(CDCl3,150 MHz):δc171.8(C-1),165.0(C-23),151.6(C-21),140.4(C-6),138.0(C-1′),134.5(C-14),129.2(C-2′),129.2(C-6′),129.1(C-3′),129.1(C-5′),128.6(C-13),127.1(C-4′),124.3(C-7),120.2(C-22),86.6(C-9),71.6(C-20),56.0(C-3),51.8(C-8),46.1(C-4),44.3(C-10),41.3(C-19),34.8(C-17),34.7(C-15),34.5(C-16),33.1(C-5),20.6(C-18),20.4(C-12),20.2(C-24),14.3(C-11).以上数据与文献[11]数据基本一致,故化合物5被确定为Cytochalasin T.

化合物6:分子式为C29H37NO5,白色粉末.1H NMR(CD3OD,600 MHz):δH7.32(2H,t,J =7.5 Hz,H-3′,5′),7.23(1H,m,H-4′),7.17(2H,m,H-2′,6′),6.09(1H,ddd,J=15.2,9.7,2.0,H-13),5.59(1H,ddd,J=15.2,10.8,3.5 Hz,H-14),5.32(1H,s,H-12a),5.04(1H,s,H-12b),4.19(1H,m,H-21),3.87(1H,d,J =9.7 Hz,H-7),3.68(1H,m,H-20),3.37(1H,m,H-3),3.00(1H,dd,J= 19.4,6.7 Hz,H-22a),2.89(1H,t,J =9.7 Hz,H-8),2.85(1H,m,H-5),2.82(1H,m,H-22b),2.77(1H,dd,J =13.2,5.9 Hz,H-10a),2.46(1H,m,H-4),2.44(1H,m,H-10b),2.16(1H,m,H-15a),1.71(1H,m,H-15b),1.47(1H,m,H-19a),1.41(1H,m,H-16),1.35(2H,m,H-18),1.20(1H,m,H-17a),1.20(1H,m,H-17b),0.96(3H,d,J =6.6 Hz,H-24),0.67(3H,d,J =6.7 Hz,H-11).13C NMR(CD3OD,150 MHz):δc208.8(C-23),176.3(C-1),150.6(C-6),139.5(C-14),138.6(C-1′),130.8(C-2′),130.8(-6′),129.7(3′),129.7(C-5′),127.8(C-4′),127.7(C-13),114.7(C-12),75.3(C-20),72.3(C-7),70.5(C-21),64.5(C-9),54.9(C-3),49.0(C-8),48.0(C-4),44.0(C-10),42.4(C-15),40.4(C-22),35.3(C-17),32.7(C-16),32.4(C-5),30.5(C-19),23.1(C-18),22.9(C-24),13.2(C-11).以上数据与文献[12]数据基本一致,故化合物6被确定为Multriostratin B.

化合物7:分子式为C29H37NO6,无色针晶.1H NMR(CD3OD,600 MHz):δH7.26(2H,t,J =7.6 Hz,H-3′,5′),7.19(1H,m,H-4′),7.13(2H,m,H-2′,6′),6.88(1H,dd,J =15.7,3.5 Hz,H-21),5.85(1H,dd,J =15.0,1.8 Hz,H-13),5.84(1H,dd,J =15.7,2.2 Hz,H-22),5.28(1H,s,H-12),5.19(1H,ddd,J=15.0,10.9,3.5 Hz,H-14),4.49(1H,m,H-20),3.79(1H,d,J =10.6 Hz,H-7),3.59(1H,m,H-19),3.40(1H,m,H-3),3.38(1H,m,H-8),3.22(1H,m,H-5),2.87(1H,dd,J =5.3,2.5 Hz,H-4),2.79(2H,d,J=6.0 Hz,H-10),2.09(1H,m,H-15a),1.64(1H,m,H-15b),1.54(1H,m,H-18a),1.54(1H,m,H-17a),1.44(1H,m,H-18b),1.16(1H,m,H-16),0.89(3H,d,J =6.6 Hz,H-24),0.87(3H,d,J =6.8 Hz,H-11),0.62(1H,m,H-17).13C NMR(CD3OD,150 MHz):δc174.0(C-1),166.2(C-23),151.4(C-21),151.4(C-6),138.1(C-1′),136.6(C-14),131.1(C-2′),131.1(C-6′),129.6(C-3′),129.6(C-5′),128.8(C-13),127.8(C-4′),119.6(C-22),114.4(C-12),85.5(C-9),75.2(C-19),74.5(C-20),71.5(C-7),54.7(C-3),44.0(C-10),43.3(C-15),35.1(C-16),33.8(C-17),32.8(C-5),31.0(C-18),20.7(C-24),14.1(C-11).以上数据与文献[13]数据基本一致,故化合物7被确定为Zopfiellasins C.

化合物8:分子式为C29H37NO6,白色固体.1H NMR(CD3OD,600 MHz):δH7.27(2H,t,J =7.5 Hz,H-3′,5′),7.19(1H,t,J=7.5 Hz,H-4′),7.14(2H,d,J =7.5 Hz,H-2′,6′),7.03(1H,dd,J =15.6,5.1 Hz,H-21),5.84(1H,dd,J =15.6,1.7 Hz,H-22),5.77(1H,ddd,J =15.0,9.7,1.6 Hz,H-13),5.30(1H,s,H-12),5.25(1H,ddd,J =15.0,10.9,3.6 Hz,H-14),5.09(1H,s,H-12),4.13(1H,m,H-20),3.80(1H,d,J=11.0 Hz,H-7),3.72(1H,t,J=7.1 Hz,H-19),3.39(1H,m,H-3),3.31(1H,m,H-8),3.19(1H,m,H-5),2.83(1H,d,J =6.0 Hz,H-4),2.14(1H,m,H-15a),1.70(1H,m,H-18),1.68(1H,m,H-15b),1.62(1H,m,H-17a),1.50(1H,m,H-18b),1.34(1H,m,H-16),0.89(3H,d,J =6.6 Hz,H-24),0.87(3H,d,J =6.8 Hz,H-11),0.80(1H,m,H-17).13C NMR(CD3OD,150 MHz):δc173.9(C-1),166.2(C-23),151.5(C-6),151.0(C-21),138.3(C-1′),136.4(C-14),131.0(C-2′),131.0(C-6′),129.6(C-3′),129.6(C-5′),128.9(C-13),127.9(4′),121.1(C-22),114.3(C-12),85.4(C-9),76.1(C-20),74.3(C-20),71.2(C-7),54.9(C-3),43.9(C-10),43.2(C-15),33.5(C-16),32.9(C-5),30.6(C-17),29.7(C-18),20.5(C-24),14.3(C-11).以上数据与文献[13]数据基本一致,故化合物8被确定为Zopfiellasins D.

化合物9:分子式为C29H37NO6,白色粉末.1H NMR(CD3OD,600 MHz):δH6.93(2H,d,J =8.5 Hz,H-2′,6′),6.89(1H,dd,J =15.7,4.1 Hz,H-21),6.67(2H,d,J =8.5 Hz,H-3′,5′),5.83(1H,ddd,J=15.0,9.7,1.6 Hz,H-13),5.76(1H,dd,J =15.7,1.8 Hz,H-22),5.28(1H,s,H-12a),5.21(1H,ddd,J =15.0,10.9,3.6 Hz,H-14),5.10(1H,s,H-12b),4.49(1H,m,H-20),3.79(1H,dd,J =10.8,1.6 Hz,H-7),3.38(1H,m,H-8),3.36(1H,m,H-5),3.23(1H,m,H-3),2.84(1H,dd,J =5.2,2.5 Hz,H-4),2.72(1H,dd,J =13.7,6.0 Hz,H-10a),2.66(1H,dd,J =13.7,5.3 Hz,H-10b),2.08(1H,m,H-15a),1.91(1H,m,H-19a),1.70(1H,m,H-15b),1.64(1H,m,H-17a),1.54(1H,m,H-19b),1.45(1H,m,H-18a),1.27(1H,m,H-16),1.20(1H,m,H-18b),0.92(3H,d,J =6.7 Hz,H-24),0.87(3H,d,J =6.6 Hz,H-11),0.56 (1H,m,H-17b).13C NMR(CD3OD,150 MHz):δc174.0(C-1),166.5(C-23),157.5(C-4′),154.8(C-21),151.5(C-6),136.6(C-14),132.1(C-2′),128.7(C-13),128.6(C-1′),119.2(C-22),116.3(C-3′),116.3(C-5′),114.3(C-12),85.5(C-9),71.5(C-7),71.1(C-20),54.9(C-3),49.9(C-8),48.2(C-4),43.2(C-10),42.8(C-19),36.6(C-17),35.3(C-15),34.6(C-16),32.9(C-5),21.4(C-18),20.7(C-24),14.2(C-11).以上数据与文献[14]数据基本一致,故化合物9被确定为Cytochalasin Z5.

4 抗炎活性检测结果

本文对分离到的化合物单体1~9均进行了抗炎活性的检测,其中化合物1、2和3有较好的抗炎活性,IC50分别为8.42,22.05和6.26μM,如表1所示.

表1 化合物1~3的抗炎活性Tab.1 The anti-inflammatory activity of compounds 1-3

5 结语

从湖北贝母内生真菌Boeremia exigua中分离得到的9 个单体化合物,均为Cytochalasan 类化合物.这类化合物的特点是有高度氢化的异吲哚母核,并骈连碳环或者内酯等大环[15]. 而且Cytochalasan 类化合物有着广泛的生物活性,例如抗炎,杀线虫,抗病原微生物,以及细胞毒等活性[16].本文报道了3个具有良好抗炎活性的Cytochalasan 类化合物的结构,其IC50值分别为8.42、22.05 和6.26 μM,为抗炎药物的开发提供了潜在的先导化合物.

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