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  • CN 31-1691/TQ

南海海绵Pseduoceratina sp.化学成分的细胞毒协同增效作用及靶点预测

竺婷婷 袁慧慧 胡瑾怡 蓝闽波

竺婷婷, 袁慧慧, 胡瑾怡, 蓝闽波. 南海海绵Pseduoceratina sp.化学成分的细胞毒协同增效作用及靶点预测[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20200828001
引用本文: 竺婷婷, 袁慧慧, 胡瑾怡, 蓝闽波. 南海海绵Pseduoceratina sp.化学成分的细胞毒协同增效作用及靶点预测[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20200828001
ZHU Tingting, YUAN Huihui, HU Jinyi, LAN Minbo. Cytotoxic Synergism and Target Prediction of Chemical Constituents from the South China Sea Sponge Pseduoceratina sp.[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20200828001
Citation: ZHU Tingting, YUAN Huihui, HU Jinyi, LAN Minbo. Cytotoxic Synergism and Target Prediction of Chemical Constituents from the South China Sea Sponge Pseduoceratina sp.[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20200828001

南海海绵Pseduoceratina sp.化学成分的细胞毒协同增效作用及靶点预测

doi: 10.14135/j.cnki.1006-3080.20200828001
基金项目: 国家自然科学基金面上项目(41576157)
详细信息
    作者简介:

    竺婷婷(1992-),女,硕士生,研究方向为天然产物活性成分的分离分析。Email:454122716@qq.com

    通讯作者:

    蓝闽波,E-mail:minbolan@ecust.edu.cn

  • 中图分类号: R285

Cytotoxic Synergism and Target Prediction of Chemical Constituents from the South China Sea Sponge Pseduoceratina sp.

  • 摘要: 以肿瘤细胞毒活性筛选为导向,采用硅胶柱色谱及高效液相色谱等现代色谱技术对南海海绵Pseduoceratina sp.化学成分进行分离纯化,并利用电喷雾质谱和核磁共振波谱等波谱技术对化合物进行结构表征;采用磺酰罗丹明B(SRB)法评价化学成分对人肺癌细胞A549、人肝癌细胞HepG2和人宫颈癌细胞HeLa的增殖抑制作用,分析化学成分和单一化合物的细胞毒活性,探讨可能的联合作用机制;采用Chemmapper Server对化合物进行靶点计算,推测作用靶点。结果表明,从南海海绵Pseduoceratina sp.中分离并鉴定得到溴代酪氨酸类生物碱hemifistularin-3( 1 )和11, 19-dideoxyfistularin 3( 2 ),2个化合物对3种肿瘤细胞的半数抑制浓度(IC50)均大于91.76 μmol/L,而以一定配比时IC50可达到8.71 μmol/L,二者对肿瘤细胞的增殖抑制具有明显的协同作用;2个化合物作用靶点可能集中在热休克转录因子1和辣椒素受体1,而协同作用可能跟化合物的多靶标作用相关。

     

  • 图  1  化合物12的结构式

    Figure  1.  Structures of compounds 1 and 2

    表  1  各组分及化合物对3种肿瘤细胞的IC50

    Table  1.   IC50 values of different fractions and compounds against three different tumour cells

    GroupIC50/(μg·mL−1)
    A549HeLaHepG2
    Fr.172.91 ± 0.0258.82 ± 0.1570.54 ± 0.03
    Fr.219.16 ± 0.049.05 ± 0.0322.24 ± 0.06
    Fr.327.35 ± 0.0116.43 ± 0.0933.43 ± 0.01
    Fr.46.12 ± 0.2013.35 ± 0.0733.10 ± 0.06
    Fr.533.91 ± 0.0120.11 ± 0.1523.00 ± 0.04
    Fr.615.21 ± 0.079.15 ± 0.049.07 ± 0.05
    Compound 193.91 ± 0.0368.23 ± 0.0396.05 ± 0.08
    Compound 299.29 ± 0.06>100>100
    5-FU30.70 ± 0.028.75 ± 0.1346.30 ± 0.07
    下载: 导出CSV

    表  2  化合物12不同配比下对3种肿瘤细胞的IC50

    Table  2.   IC50 values of mixed compounds 1 and 2 against different cell lines

    n(Compound 1):
    n(Compound 2)
    IC50 /(μmol·L−1)
    A549HeLaHepG2
    2:1 28.09 ± 0.08 25.20 ± 0.13 30.88 ± 0.02
    1:1 11.41 ± 0.03 11.43 ± 0.09 14.90 ± 0.01
    1:2 8.71 ± 0.06 9.73 ± 0.06 27.55 ± 0.05
    1:3 25.62 ± 0.03 18.10 ± 0.10 38.86 ± 0.09
    1:4 22.05 ± 0.04 13.98 ± 0.14 31.00 ± 0.01
    Compound 1 >100 >100 >100
    Compound 2 91.76 ± 0.06 >100 >100
    下载: 导出CSV

    表  3  化合物12不同配比的CI

    Table  3.   CI values of mixed compounds 1 and 2

    n(Compound 1):
    n(Compound 2)
    CI
    A549HeLaHepG2
    2:10.3210.2100.279
    1:10.2810.1640.242
    1:20.2740.1580.271
    1:30.3150.1860.298
    1:40.3210.2100.279
    下载: 导出CSV

    表  4  化合物1预测靶标

    Table  4.   Predicted targets of compound 1

    Target nameSpeciesScore
    Vanilloid Receptor 1
    (TRPV1, VR1)
    Rattus norvegicus1.000
    Hsf1 proteinMus musculus0.758
    Vanilloid Receptor 1
    (TRPV1, VR1)
    Homo sapiens0.729
    Carboxy-terminal domain
    RNA polymerase II polypeptide A
    small phosphatase 1 isoform 1
    Homo sapiens0.649
    Glycogen synthase kinase
    3 beta isoform 1
    Homo sapiens0.660
    HIV-1 IntegraseHuman mmunodeficiency virus 10.604
    Histamine H3 ReceptorHomo sapiens0.584
    Metabotropic
    glutamate receptor 1
    Rattus norvegicus0.538
    Beta-2 adrenergic receptorHomo sapiens0.509
    LANAHuman herpesvirus 80.447
    下载: 导出CSV

    表  5  化合物2预测靶标

    Table  5.   Predicted targets of compound 2

    Target nameSpeciesScore
    Vanilloid Receptor 1 (TRPV1, VR1)Homo sapiens1.000
    Histamine H3 ReceptorHomo sapiens0.772
    Hsf1 proteinMus musculus0.701
    Platelet activating factor receptorHomo sapiens0.563
    Adenosine A1 receptorRattus norvegicus0.486
    Thromboxane-A synthaseHomo sapiens0.473
    GABA receptor alpha-1/ alpha-2/ alpha-3/ alpha-4/beta-1/gamma-2 subunitBos Taurus0.394
    Epoxide hydrataseHomo sapiens0.356
    Phosphoglycerate kinase 1/2Homo sapiens0.343
    Streptokinase A precursorStreptococcus pyogenes M1 GAS0.329
    下载: 导出CSV
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出版历程
  • 收稿日期:  2020-08-28
  • 网络出版日期:  2020-12-16

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