高级检索

水飞蓟宾衍生物的设计、合成及体外抗肿瘤活性

李雁, 高磊, 张朝会, 孟艳秋

李雁，高磊，张朝会，等. 水飞蓟宾衍生物的设计、合成及体外抗肿瘤活性[J]. 中国药科大学学报，2025，56（3）：305 − 311. DOI: 10.11665/j.issn.1000-5048.2024041701
引用本文: 李雁，高磊，张朝会，等. 水飞蓟宾衍生物的设计、合成及体外抗肿瘤活性[J]. 中国药科大学学报，2025，56（3）：305 − 311. DOI: 10.11665/j.issn.1000-5048.2024041701
shu
LI Yan, GAO Lei, ZHANG Chaohui, et al. Design, synthesis, and in vitro anti-tumor activity of silybin derivatives[J]. J China Pharm Univ, 2025, 56(3): 305 − 311. DOI: 10.11665/j.issn.1000-5048.2024041701
Citation: LI Yan, GAO Lei, ZHANG Chaohui, et al. Design, synthesis, and in vitro anti-tumor activity of silybin derivatives[J]. J China Pharm Univ, 2025, 56(3): 305 − 311. DOI: 10.11665/j.issn.1000-5048.2024041701
shu

水飞蓟宾衍生物的设计、合成及体外抗肿瘤活性

  • 沈阳化工大学化学工程学院 沈阳 110142

基金项目: 

国家自然科学基金项目（No.82473787）；辽宁省重点研发计划项目(2019JH2/10300034)；沈阳市重大科技成果转化项目(20-203-5-45)

undefined

详细信息
    通讯作者:

    孟艳秋: Tel：15940588671　E-mail：myq6581@163.com

  • 中图分类号: R914.5

Design, synthesis, and in vitro anti-tumor activity of silybin derivatives

  • School of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China

Funds: 

undefined

This study was supported by the National Natural Science Foundation of China (No.82473787); Liaoning Provincial Key Research and Development Project (2019JH2/10300034); and Shenyang Major Scientific and Technological Achievement Transformation Project (20-203-5-45)

HTML全文

    摘要
  • 摘要:

    以天然黄酮类化合物水飞蓟宾为母体，通过氧化脱氢、烷基化、选择性去甲基、酰化等反应共合成了16个水飞蓟宾衍生物，其结构均通过1H NMR、13C NMR、MS确证，确定均为未经文献报道的新化合物。选用胃癌细胞SGC-7901和人胶质母细胞瘤细胞LN-229，采用MTT法，以拉帕替尼为阳性对照药测定新型水飞蓟宾衍生物的体外抗肿瘤活性。实验结果表明，合成的新型水飞蓟宾衍生物对两种癌细胞有一定程度的抗增殖作用，其中化合物I2和I14对LN-229细胞和SGC-7901细胞显示较强的抗增殖活性。

    Abstract:

    This study used the natural flavonoid compound silybin as the parent compound and synthesized 16 silybin derivatives through oxidative dehydrogenation, alkylation, selective demethylation, and acylation. The structures of these derivatives were confirmed by 1H NMR, 13C NMR, and MS. All derivatives were found to be new compounds never reported in previous literature. Using gastric cancer cell line SGC-7901 and human glioblastoma cell line LN-229, the in vitro anti-tumor activity of the novel silybin derivative was determined through MTT assay with lapatinib as the positive control. The experimental results indicate that the synthesized novel silybin derivatives have a certain degree of anti-proliferative effect on two types of cancer cells, with compounds I2 and I14 showing strong anti-proliferative activity against LN-229 and SGC-7901 cells.

    • HTML全文

  • 1.   Synthesis route of the target compound I1−I16

    Reagents and conditions:(a)pyridine, 110 °C, 24 h; (b) ICH3, NaH, TBAI, DMF, 80 °C, 3 h; (c) AlCl3, TBAI, 1, 2-dichloroethane-acetonitrile(1∶1), 70 °C, 3 h; (d) R-Cl, NaH, DMAP, 0 °C, 1.5 h; R-O-R, DMAP, pyridine, r.t., 1.5 h; R-Br, NaH, TBAI, DMF, 80 °C, 3 h

    下载: 全尺寸图片 幻灯片

    Table  1   Yield, melting point and MS data of target compounds

    Compd. Yield% Melting/°C ESI-MS m/z[M+H]+
    SB-1 62.0 230.2−233.5 481.43
    SB-2 93.0 98.0−102.0 551.55
    SB-3 86.0 114.3−119.5 537.53
    I1 94.0 198.6−202.1 613.63
    I2 91.1 155.4−158.3 641.64
    I3 87.2 148.2−153.0 655.67
    I4 89.3 132.1−134.0 676.08
    I5 92.3 158.6−162.7 579.57
    I6 85.6 223.2−225.1 669.7
    I7 88.5 163.2−165.6 671.67
    I8 90.1 183.4−186.7 655.67
    I9 84.7 127.3−130.6 676.08
    I10 91.3 153.4−156.2 710.53
    I11 92.4 175.3−178.2 677.62
    I12 86.8 241.0−244.3 647.69
    I13 91.6 130.9−133.3 635.68
    I14 87.1 257.8−259.2 631.6
    I15 89.0 130.5−133.6 691.72
    I16 96.1 148.5−152.3 709.64
    下载: 导出CSV

    Table  2   1H NMR and 13C NMR data of target compounds

    Compd. 1H NMR (500 MHz) 13C NMR (125 MHz)
    SB-1 (DMSO-d6) δ: 12.42 (1H, s, 5-OH), 10.81(1H, s, 7-OH), 9.56 (1H, s, 3-OH), 9.16 (1H, s, 20-OH), 7.77 (1H, t, J = 2.1 Hz, Ar-H), 7.75 (1H, d, J = 2.2 Hz, , Ar-H), 7.12 (1H, d, J = 8.5 Hz, Ar-H), 7.05 (1H, d, J =2.0 Hz, , Ar-H), 6.89 (1H, dd, J = 8.2, 2.0 Hz, Ar-H), 6.82 (1H, d, J = 8.0 Hz, Ar-H), 6.46 (1H, d, J = 2.0 Hz, Ar-H), 6.20 (1H, d, J = 2.0 Hz, Ar-H), 4.99 (1H, t, J = 5.6 Hz, 11-H), 4.97 (1H, d, J = 7.9 Hz, 23-OH), 4.28-4.26 (1H, m, 10-H), 3.80 (3H, s, -OCH3), 3.58 (1H, ddd, J = 12.3, 5.0, 2.5 Hz, 23-H), 3.40−3.35 (1H, m, 23-H) (Chloroform-d) δ: 176.94, 165.06, 161.65, 157.55, 148.16, 147.30, 145.78, 145.35, 144.51, 136.45, 128.61, 124.54, 122.88, 121.28, 116.85, 116.13, 115.56, 112.00, 102.98, 99.88, 94.59, 78.04, 76.90, 61.51, 56.16
    SB-2 (Chloroform-d) δ: 7.77–7.70 (2H, m, Ar-H), 7.10 (1H, d, J = 8.6 Hz, Ar-H), 7.02 (1H, d, J = 8.2 Hz, Ar-H), 6.97–6.91 (2H, m, Ar-H), 6.47 (1H, d, J = 2.3 Hz, Ar-H), 6.32 (1H, d, J = 2.3 Hz, Ar-H), 5.05 (1H, d, J = 8.0 Hz, 11-H), 4.20-4.18 (1H, m, 10-H), 3.95 (3H, s, 5-OCH3), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.89 (3H, s, 19-OCH3), 3.87 (3H, s, 20-OCH3), 3.62 (1H, dd, J = 5.5, 5.0 Hz, 23-H), 3.36 (3H, s, 23-OCH3), 3.32 (1H, dd, J = 6.4, 4.5Hz, 23-H) (DMSO-d6) δ: 178.84, 165.49, 160.95, 156.75, 155.35, 149.76, 149.41, 146.01, 143.75, 139.20, 128.53, 123.69, 122.44, 120.13, 117.47, 111.32, 110.20, 106.09, 97.91, 92.05, 77.28, 76.32, 71.22, 59.77, 59.08, 56.08, 55.97
    SB-3 (Chloroform-d) δ: 12.61 (1H, s, 5-OH), 7.77 (1H, d, J = 2.1 Hz, Ar-H), 7.73 (1H, dd, J = 8.6, 2.2 Hz, Ar-H), 7.12 (1H, d, J = 8.6 Hz, Ar-H), 7.02 (1H, d, J = 8.3 Hz, Ar-H), 6.94 (2H, s, Ar-H), 6.41 (1H, d, J = 2.1 Hz, Ar-H), 6.34 (1H, d, J = 2.2 Hz, Ar-H), 5.07–5.04 (1H, m, 11-H), 4.21–4.18 (1H, m, 10-H), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.88 (3H, s, 19-OCH3), 3.85 (3H, s, 20-OCH3), 3.62 (1H, dd, J = 5.4, 4.5 Hz, 23-H), 3.37 (3H, s, 23-OCH3), 3.33 (1H, dd, J = 4.5, 4.0 Hz, 23-H) (Chloroform-d) δ: 178.84, 165.49, 162.00, 156.75, 155.35, 149.76, 149.40, 146.00, 143.76, 139.19, 128.53, 123.69, 122.44, 120.13, 117.47, 111.32, 110.20, 106.09, 97.91, 92.05, 78.05, 76.30, 71.10, 60.18, 59.55, 56.03, 56.01, 55.79
    I1 (DMSO-d6) δ: 7.69 (2H, d, J = 6.7 Hz, Ar-H), 7.63 (2H, d, J = 7.0 Hz, Ar-H), 7.42 (2H, t, J = 7.5 Hz, Ar-H), 7.33 (1H, t, J = 7.3 Hz, Ar-H), 7.14 (1H, d, J = 9.2 Hz, Ar-H), 7.10 (1H, s, Ar-H), 7.02 (2H, s, Ar-H), 6.86 (1H, d, J = 2.3 Hz, Ar-H), 6.57 (1H, d, J = 2.3 Hz, Ar-H), 5.23 (2H, s, Ar-CH2-), 5.00 (1H, d, J = 8.0 Hz, 11-H), 4.52–4.48 (1H, m, 10-H), 3.86 (3H, s, 3-OCH3), 3.79 (6H, s, 7-OCH3, 19-OCH3), 3.78 (3H, s, 20-OCH3), 3.46 (1H, dd, J = 5.0, 5.4 Hz, 23-H), 3.28 (1H, dd, J = 5.0, 5.5 Hz, 23-H), 3.23 (3H, s, 23-OCH3) (DMSO-d6) δ: 172.73, 164.09, 159.46, 158.64, 151.62, 149.77, 149.32, 145.61, 143.93, 141.04, 137.29, 128.86, 128.80, 127.97, 127.31, 123.72, 122.12, 120.82, 117.46, 116.89, 112.04, 111.63, 109.25, 97.79, 93.80, 77.26, 76.31, 71.24, 70.36, 59.80, 59.09, 56.47, 56.08, 55.97
    I2 (Chloroform-d) δ: 8.27 (2H, d, J = 4.0 Hz, Ar-H), 8.02 (2H, d, J = 5.2 Hz, Ar-H), 7.80 (1H, d, J = 4.4 Hz, Ar-H), 7.59–7.57 (1H, m, Ar-H), 7.52 (1H, d, J = 1.0 Hz, Ar-H), 7.10(1H, d, J = 8.0 Hz, Ar-H), 7.01–6.98 (1H, m, Ar-H), 6.92 (1H, d, J = 4.5 Hz, Ar-H), 6.89(1H, d, J = 8.0 Hz, Ar-H), 6.85 (1H, d, J = 1.8 Hz, Ar-H), 6.72 (2H, d, J = 1.8 Hz, Ar-H), 5.09 (1H, d, J = 6.1 Hz, 11-H), 4.50–4.47 (1H, m, 10-H), 4.27 (1H, dd, J = 4.4, 4.0 Hz, 23-H), 3.91 (3H, s, 3-OCH3), 3.87 (3H, s, 7-OCH3), 3.82 (3H, s, 19-OCH3), 3.77 (3H, s, 20-OCH3), 3.37 (3H, s, 23-OCH3), 3.32 (1H, dd, J = 4.5, 4.0 Hz, 23-H) (DMSO-d6) δ: 172.42, 163.94, 163.63, 157.69, 157.51, 153.41, 150.13, 149.77, 45.99, 144.00, 140.63, 133.71, 130.73, 130.67, 129.14, 128.81, 127.54, 127.49, 123.42, 122.44, 120.84, 116.58, 116.36, 112.04, 111.63, 111.15, 104.70, 99.92, 77.30, 76.33, 71.23, 59.94, 59.09, 56.92, 56.07, 55.97
    I3 (Chloroform-d) δ: 8.33 (1H, dd, J = 7.8, 1.5 Hz, Ar-H), 7.76 (1H, d, J = 2.1 Hz, Ar-H), 7.72 (1H, dd, J = 8.6, 2.2 Hz, Ar-H), 7.46 (1H, dd, J = 7.5, 8.0 Hz, Ar-H), 7.35–7.29 (2H, m, Ar-H), 7.12 (1H, d, J = 8.6 Hz, Ar-H), 7.02 (1H, dd, J = 8.2, 1.9 Hz, Ar-H), 6.97–6.92 (2H, m, Ar-H), 6.84 (1H, d, J = 2.5 Hz, Ar-H), 6.69 (1H, d, J = 2.4 Hz, Ar-H), 5.06 (1H, d, J = 8.1 Hz, 11-H), 4.21–4.18 (1H, m, 10-H), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.91 (3H, s, 19-OCH3), 3.78 (3H, s, 20-OCH3), 3.62 (1H, dd, J =5.5, 5.0 Hz, 23-H), 3.37 (3H, s, 23-OCH3), 3.32 (1H, dd, J = 4.5, 3.0 Hz, 23-H), 2.67 (3H, s, Ar-CH3) (DMSO-d6) δ: 172.49, 165.42, 163.68, 157.73, 157.68, 153.36, 150.24, 149.77, 149.31, 145.98, 144.01,140.65, 140.56, 133.14, 132.10, 131.63, 129.20, 128.82, 126.48, 123.46, 122.44, 120.85, 117.56, 117.17, 112.03, 111.63, 111.31, 99.80, 77.29, 76.33, 71.23, 59.90, 59.09, 56.92, 56.02, 55.97, 21.45
    I4 (Chloroform-d) δ: 7.93 (1H, d, J = 8.5 Hz, Ar-H), 7.75 (1H, d, J = 2.0 Hz, Ar-H), 7.49 (3H, dd, J = 8.6, 1.5 Hz, Ar-H), 7.43 (2H, d, J = 8.6 Hz, Ar-H), 7.02 (1H, dd, J = 8.2, 2.0 Hz, Ar-H), 6.96 -6.99 (2H, m, Ar-H), 6.85 (1H, dd, J = 4.5, 4.0 Hz, Ar-H), 6.71 (1H, t, J = 5.6 Hz, Ar-H), 5.04 (1H, d, J = 7.8 Hz, 11-H), 4.24–4.15 (1H, m, 10-H), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.85 (3H, s, 19-OCH3), 3.76 (3H, s, 20-OCH3), 3.63 (1H, dd, J = 4.5, 4.1 Hz, 23-H), 3.37 (3H, s, 23-OCH3), 3.33 (1H, dd, J = 5.5, 4.1 Hz, 23-H) (DMSO-d6) δ: 171.34, 162.79, 161.97, 157.67, 157.45, 152.72, 149.77, 149.31, 146.22, 145.98, 143.99, 140.80, 132.30, 130.36, 129.05, 128.79, 123.25, 122.39, 120.85, 117.54, 117.09, 112.03, 111.82, 111.63, 109.25, 101.02, 77.28, 76.32, 71.22, 59.77, 59.09, 56.98, 56.08, 56.04, 55.97
    I5 (Chloroform-d) δ: 7.75 (1H, d, J = 2.1 Hz, Ar-H), 7.71 (1H, d, J = 8.7 Hz, Ar-H), 7.12 (1H, d, J = 8.7 Hz, Ar-H), 7.02 (1H, dd, J = 8.2, 2.0 Hz, Ar-H), 6.98–6.91 (2H, m, Ar-H), 6.79 (1H, d, J = 2.4 Hz, Ar-H), 6.58 (1H, d, J = 2.5 Hz, Ar-H), 5.06 (1H, d, J = 8.1 Hz, 11-H), 4.21–4.17 (1H, m, 10-H), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.88 (3H, s, 19-OCH3), 3.81 (3H, s, 20-OCH3), 3.62 (1H, dd, J = 5.5, 5.0 Hz, 23-H), 3.37 (3H, s, 23-OCH3), 3.32 (1H, dd, J = 4.5, 4.0Hz, 23-H), 2.45 (3H, s, -COCH3) (DMSO-d6) δ: 172.73, 169.05, 164.08, 159.46, 159.01, 151.62, 149.77, 149.32, 145.61, 143.93, 137.29, 127.97, 123.72, 122.12, 120.82, 117.47, 116.88, 112.04, 111.63, 111.08, 109.25, 97.79, 77.27, 76.31, 71.24, 59.80, 59.08, 56.46, 56.08, 55.97, 20.62
    I6 (Chloroform-d) δ: 7.71 (1H, dd, J = 5.1, 1.6 Hz, Ar-H), 7.33–7.31 (4H, m, Ar-H), 7.24–7.19 (2H, m, Ar-H), 7.12 (1H, dd, J =4.4, 3.2 Hz, Ar-H), 7.02 (1H, dd, J =4.4 , 2.1 Hz, Ar-H), 6.98–6.90 (3H, m, Ar-H), 6.76 (1H, d, J = 1.9 Hz, Ar-H), 5.01 (1H, d, J = 6.1 Hz, 11-H), 4.21–4.18 (1H, m, 10-H), 3.92(6H, s, 3-OCH3, 7-OCH3), 3.87(3H, s, 19-OCH3), 3.81(3H, s, 20-OCH3), 3.63 (1H, dd, J = 6.7, 2.0 Hz, 23-H), 3.37(3H, s, 23-OCH3), 3.33 (1H, dd, J = 8.0, 5.3 Hz, 23-H), 3.17–3.09 (4H, m, -CH2-CH2-) (DMSO-d6) δ: 172.49, 171.23, 163.57, 157.72, 153.35, 150.18, 149.76, 149.30, 145.98, 143.99, 140.87, 140.67, 128.88, 128.66, 128.53, 125.74, 123.42, 122.44, 120.85, 117.57, 117.17, 112.03, 111.61, 111.09, 105.11, 99.63, 77.28, 76.32, 71.22, 59.96, 59.09, 56.88, 56.07, 55.97, 35.41, 30.34
    I7 (Chloroform-d) δ: 7.97–7.91 (2H, m, Ar-H), 7.76–7.74 (1H, m, Ar-H), 7.48 (3H, dd, J = 6.4, 1.2 Hz, Ar-H), 7.02 (1H, dd, J = 6.2, 1.5 Hz, Ar-H), 6.98–6.96 (2H, m, Ar-H), 6.87–6.84 (2H, m, Ar-H), 6.71 (1H, t, J = 6.1 Hz, Ar-H), 5.04 (1H, d, J = 5.8 Hz, 11-H), 4.21-4.19 (1H, m, 10-H), 3.92(6H, s, 3-OCH3, 7-OCH3), 3.87(3H, s, 19-OCH3), 3.84(3H, s, 20-OCH3), 3.76(3H, s, Ar-OCH3), 3.62 (1H, dd, J = 8.3, 1.7 Hz, 23-H), 3.37(3H, s, 23-OCH3), 3.33 (1H, dd, J = 4.0, 4.4 Hz, 23-H) (DMSO-d6) δ: 163.73, 163.25, 156.52, 155.90, 153.50, 149.83, 149.40, 149.37, 148.85, 146.09, 140.73, 133.66, 128.88, 123.49, 122.55, 120.94, 120.54, 117.67, 117.26, 114.05, 112.10, 111.69, 109.15, 104.76, 100.16, 77.36, 76.41, 71.31, 60.08, 59.18, 57.04, 56.16, 56.05, 55.86
    I8 (DMSO-d6) δ: 7.75 (1H, d, J = 1.3 Hz, Ar-H), 7.73 (1H, d, J = 1.6 Hz, Ar-H), 7.47 (1H, d, J = 5.3 Hz, Ar-H), 7.42 (1H, d, J = 1.6 Hz, Ar-H), 7.38–7.35 (2H, m, Ar-H), 7.18 (2H, dd, J = 7.0, 1.6 Hz, Ar-H), 7.10(1H, s, Ar-H), 7.02(2H, s, Ar-H), 6.83 (1H, d, J = 6.0 Hz, Ar-H), 6.76 (1H, d, J = 1.8 Hz, Ar-H), 5.02 (1H, d, J = 8.0 Hz, 11-H), 4.56–4.51 (1H, m, 10-H), 3.84 (2H, d, J = 9.4 Hz, Ar-CH2-), 3.79 (6H, s, 3-OCH3, 7-OCH3), 3.78 (3H, s, 19-OCH3), 3.77 (3H, s, 20-OCH3), 3.47 (1H, dd, J = 9.2, 7.5Hz, 23-H), 3.30 (1H, dd, J = 6.5, 5.0Hz, 23-OCH3), 3.23 (3H, s, 23-H) (DMSO-d6) δ: 172.62, 165.55, 163.81, 157.87, 153.50, 150.37, 149.91, 149.45, 146.12, 144.14, 140.80, 140.70, 131.77, 129.51, 129.40, 126.62, 123.59, 122.57, 120.99, 117.70, 117.31, 112.17, 111.77, 111.45, 109.16, 99.93, 77.43, 76.47, 71.37, 60.04, 59.23, 57.06, 56.22, 56.11, 34.99
    I9 (Chloroform-d) δ: 8.14–8.10 (1H, m, Ar-H), 7.98 (1H, d, J = 1.5 Hz, Ar-H), 7.76 (1H, dd, J = 8.5, 1.7 Hz, Ar-H), 7.51–7.48 (1H, m, Ar-H), 7.44–7.41 (2H, m, Ar-H), 7.04–6.95 (4H, m, Ar-H), 6.85 (1H, t, J = 1.5 Hz, Ar-H), 6.71 (1H, dd, J = 5.2, 4.0 Hz, Ar-H), 5.04 (1H, d, J = 5.8 Hz, 11-H), 4.21–4.17 (1H, m, 10-H), 3.92(6H, s, 3-OCH3, 7-OCH3), 3.87(3H, s, 19-OCH3), 3.76(3H, s, 20-OCH3), 3.62 (1H, dd, J = 8.2, 1.5 Hz, 23-H), 3.37(3H, s, 23-OCH3), 3.33 (1H, dd, J = 8.2, 1.7 Hz, 23-H) (DMSO-d6) δ: 172.33, 171.07, 163.41, 157.56, 157.02, 153.19, 149.60, 149.14, 145.82, 143.83, 140.71, 134.33, 132.58, 129.48, 128.72, 128.50, 128.37, 128.10, 123.26, 122.28, 120.69, 117.40, 117.01, 111.87, 111.45, 110.94, 104.95, 99.47, 77.12, 76.16, 71.06, 59.80, 58.93, 56.72, 55.91, 55.81
    I10 (DMSO-d6) δ: 8.30 (1H, d, J = 6.4 Hz, Ar-H), 7.87 (1H, d, J = 1.6 Hz, Ar-H), 7.74 (2H, d, J = 1.6 Hz, Ar-H), 7.71 (1H,d, J = 1.6 Hz, Ar-H), 7.69 (1H, d, J = 1.6 Hz, Ar-H), 7.35 (1H, d, J = 1.8 Hz, Ar-H), 7.18–7.16 (1H, m, Ar-H), 7.09 (1H, s, Ar-H), 7.01 (1H, s, Ar-H), 6.95 (1H, d, J = 1.8 Hz, Ar-H), 5.01 (1H, d, J = 6.0 Hz, 11-H), 4.23–4.16 (1H, m, 10-H), 3.92 (3H, s, 3-OCH3), 3.78 (6H, s, 7-OCH3, 19-OCH3), 3.70 (3H, s, 20-OCH3), 3.46 (1H, dd, J = 5.0, 4.5 Hz, 23-H), 3.29 (1H, dd, J = 4.5, 4.0 Hz, 23-H), 3.22 (3H, s, 23-OCH3) (DMSO-d6) δ: 172.65, 166.44, 163.85, 157.84, 157.40, 153.73, 149.90, 149.44, 146.17, 144.14, 140.05, 137.72, 134.42, 133.09, 130.43, 128.93, 127.23, 126.52, 123.51, 122.61, 120.97, 117.70, 117.33, 112.15, 111.74, 110.99, 109.08, 100.28, 77.31, 76.33, 71.22, 59.95, 59.09, 56.99, 56.07, 55.96
    I11 (DMSO-d6) δ: 8.31 (1H, d, J = 8.5 Hz, Ar-H), 7.90–7.84 (2H, m, Ar-H), 7.80–7.77 (1H, m, Ar-H), 7.55 (1H, dd, J = 8.4, 2.1 Hz, Ar-H), 7.36 (1H, d, J = 2.5 Hz, Ar-H), 7.19 (2H, t, J = 8.8 Hz, Ar-H), 7.06 (1H, d, J = 8.4 Hz, Ar-H), 6.97 (1H, t, J = 2.2 Hz, Ar-H), 6.69 (1H, d, J = 8.0 Hz, Ar-H), 5.03 (1H, d, J = 8.0 Hz, 11-H), 4.55–4.52 (1H, m, 10-H), 3.79 (6H, d, J = 2.3 Hz, 3-OCH3, 7-OCH3), 3.75(3H, s, 19-OCH3), 3.71(3H, s, 20-OCH3), 3.47 (1H, dd, J = 8.5, 4.0 Hz, 23-H), 3.29 (1H, d, J = 4.7 Hz, 23-H), 3.23(3H, s, 23-OCH3) (DMSO-d6) δ: 172.42, 166.08, 163.92, 163.63, 161.00, 157.69, 157.08, 153.41, 149.77, 149.32, 145.99, 144.00, 140.63, 133.35, 128.81, 123.42, 122.44, 120.84, 116.58, 116.36, 115.22, 112.04, 111.63, 111.15, 109.00, 105.34, 105.12, 99.92, 77.30, 76.33, 71.23, 59.94, 59.09, 56.92, 56.07, 55.97
    I12 (DMSO-d6) δ: 8.20 (1H, d, J = 3.1 Hz, Ar-H), 7.72 (1H, d, J = 7.3 Hz, Ar-H), 7.47 (2H, t, J = 8.0 Hz, Ar-H), 7.17 (1H, d, J = 9.4 Hz, Ar-H), 7.10 (1H, s, Ar-H), 7.02 (1H, s, Ar-H), 6.95(1H, d, J = 2.5 Hz, Ar-H), 5.02 (1H, d, J = 8.0 Hz, 11-H), 4.56–4.51 (1H, m, 10-H), 3.92 (3H, s, 3-OCH3), 3.79 (6H, s, 7-OCH3, 19-OCH3), 3.67 (3H, s, 20-OCH3), 3.47 (1H, dd, J = 4.0, 4.5 Hz, 23-H), 3.31 (1H, d, J = 4.0Hz, 23-H), 3.23 (3H, s, 23-OCH3), 2.08–2.02 (1H, m, -CH-), 1.74–1.59 (4H, m, 2(-CH2-)), 1.52–1.42 (2H, m, -CH2-), 1.36–1.20 (4H, m, 2(-CH2-)) (DMSO-d6) δ: 172.42, 171.54, 163.63, 157.69, 153.41, 150.13, 149.77, 149.32, 145.99, 144.00, 140.63, 128.81, 123.42, 122.44, 120.84, 116.58, 116.36, 112.04, 111.63, 111.15, 109.00, 99.92, 77.30, 76.33, 71.23, 59.94, 59.09, 56.92, 56.07, 55.97, 43.86, 29.13, 25.58, 25.49
    I13 (DMSO-d6) δ: 7.70-7.71 (2H, m, Ar-H), 7.27 (1H, d, J = 2.4 Hz, Ar-H), 7.17 (1H, d, J = 9.2 Hz, Ar-H), 7.10 (1H, s, Ar-H), 7.02 (2H, s, Ar-H), 6.74 (1H, d, J = 2.4 Hz, Ar-H), 5.02 (1H, d, J = 8.0 Hz, 11-H), 4.53-4.51 (1H, m, 10-H), 3.90 (3H, s, 3-OCH3), 3.79 (6H, d, J = 2.3 Hz, 7-OCH3, 19-OCH3), 3.73 (3H, s, 20-OCH3), 3.47 (1H, dd, J = 9.5, 5.0 Hz, 23-H), 3.30 (1H, d, J = 6.5 Hz, 23-H), 3.23 (3H, s, 23-OCH3), 2.66 (2H, t, J=7.5 Hz, -CH2-), 1.70–1.64 (2H, m, -CH2-), 1.39–1.35 (4H, m, -CH2-CH2-), 0.92 (3H, t, J = 6.9 Hz, -CH3) (DMSO-d6) δ: 172.52, 166.31, 163.72, 162.37, 157.71, 153.60, 149.77, 149.31, 146.04, 144.01, 128.80, 123.38, 122.48, 120.84, 117.57, 117.20, 112.02, 111.61, 110.86, 108.95, 100.15, 77.31, 76.33, 71.22, 59.95, 59.09, 56.07, 55.96, 34.85, 30.88, 24.50, 22.19, 14.03
    I14 (Chloroform-d) δ: 8.28 (2H, dd, J = 8.6, 5.5 Hz, Ar-H), 7.76–7.70 (2H, m, Ar-H), 7.18 (2H, t, J = 8.4 Hz, Ar-H), 7.12 (1H, d, J = 8.6 Hz, Ar-H), 7.02 (1H, d, J = 8.2 Hz, Ar-H), 6.97–6.92 (2H, m, Ar-H), 6.84 (1H, d, J = 2.5 Hz, Ar-H), 5.06 (1H, d, J = 8.1 Hz, 11-H), 4.21–4.17 (1H, m, 10-H), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.90 (3H, s, 19-OCH3), 3.75 (3H, s, 20-OCH3), 3.62 (1H, dd, J = 11.0, 2.2 Hz, 23-H), 3.37 (3H, s, 23-OCH3), 3.33 (1H, dd, J = 7.3, 5.0 Hz, 23-H) (DMSO-d6) δ: 172.33, 163.64, 157.66, 156.43, 155.81, 153.41, 149.74, 149.31, 149.28, 148.76, 146.00, 144.00, 140.64, 133.57, 128.79, 123.40, 122.46, 120.85, 120.45, 117.58, 117.17, 112.01, 111.60, 109.06, 100.07, 77.27, 76.32, 71.22, 59.99, 59.09, 56.95, 56.07, 55.96
    I15 (Chloroform-d) δ: 8.00 (1H, s, Ar-H), 7.98 (1H, s, Ar-H), 7.73 (1H, d, J = 2.1 Hz, Ar-H), 7.69 (1H, dd, J = 8.7, 2.2 Hz, Ar-H), 7.32 (2H, d, J = 8.1 Hz, Ar-H), 7.10 (1H, d, J = 8.6 Hz, Ar-H), 7.04–7.01 (1H, m, Ar-H), 6.96–6.92 (2H, m, Ar-H), 6.83–6.81 (2H, m, Ar-H), 5.05 (1H, d, J = 8.2 Hz, 11-H), 4.20–4.17 (1H, m, 10-H), 3.92 (6H, s, 3-OCH3, 7-OCH3), 3.87 (3H, s, 19-OCH3), 3.79 (3H, s, 20-OCH3), 3.62 (1H, dd, J = 5.4, 4.5 Hz, 23-H), 3.36 (3H, s, 23-OCH3), 3.32 (1H, dd, J =5.5, 5.0 Hz, 23-H), 2.42 (3H, s, Ar-CH3) (DMSO-d6) δ: 171.34, 162.79, 157.67, 152.72, 149.77, 149.31, 147.30, 146.22, 145.98, 143.99, 140.80, 132.30, 130.36, 129.05, 128.79, 123.25, 122.39, 120.85, 117.54, 117.09, 112.03, 111.82, 111.63, 109.25, 101.02, 77.28, 76.32, 71.22, 59.77, 59.09, 56.98, 56.04, 56.03, 21.59
    I16 (Chloroform-d) δ: 8.38 (1H, d, J = 6.1 Hz, Ar-H), 7.81–7.74 (3H, m, Ar-H), 7.72 (1H, dd, J = 6.5, 1.6 Hz, Ar-H), 7.12 (1H, dd, J = 6.5, 1.8 Hz, Ar-H), 7.02 (1H, dd, J = 6.2, 1.5 Hz, Ar-H), 6.97–6.93 (2H, m, Ar-H), 6.86 (1H, d, J = 1.8 Hz, Ar-H), 6.73 (1H, d, J = 1.8 Hz, Ar-H), 6.38 (1H, dd, J = 6.1, 1.7 Hz, Ar-H), 5.06 (1H, d, J = 6.0 Hz, 11-H), 4.21–4.18 (1H, m, 10-H), 3.92(6H, s, 3-OCH3, 7-OCH3), 3.89(3H, s, 19-OCH3), 3.86(3H, s, 20-OCH3), 3.63 (1H, dd, J = 4.5, 4.0Hz, 23-H), 3.37(3H, s, 23-OCH3), 3.33 (1H, dd, J = 5.5, 4.1Hz, 23-H) (Chloroform-d) δ: 178.84, 165.70, 165.49, 162.00, 156.75, 155.36, 149.76, 149.41, 146.01, 143.75, 139.20, 136.08, 135.65, 135.05, 134.41, 131.04, 131.01, 129.55, 128.53, 126.52, 126.36, 123.69, 122.48, 122.44, 121.58, 120.90, 120.13, 119.60, 117.47, 116.80, 112.06, 111.32, 110.20, 106.09, 97.91, 78.05, 76.30, 71.10, 60.18, 59.55, 56.03, 56.00, 55.78
    下载: 导出CSV

    Table  3   In vitro inhibitory activity of target compounds on SGC-7901 and LN-229

    Compd. Inhibitiona/% IC50b/(μmol/L)
    LN-229 SGC-7901 LN-229 SGC-7901
    I1 18.7 17.4 >50 >50
    I2 51.4 48.1 8.78 12.54
    I3 48.1 48.7 12.54 16.35
    I4 40.1 38.1 16.59 18.03
    I5 47.9 43.2 12.98 15.86
    I6 20.3 22.4 30.01 29.98
    I7 25.1 24.3 27.31 26.79
    I8 19.8 18.6 36.47 45.16
    I9 48.7 49.5 11.91 11.66
    I10 33.9 34.1 20.46 19.81
    I11 34.6 35.4 18.33 18.56
    I12 39.2 42.8 17.53 15.41
    I13 44.8 48.2 14.31 12.03
    I14 49.6 50.8 11.59 9.16
    I15 38.8 34.2 17.59 15.53
    I16 43.3 40.5 17.05 16.71
    Silybin 20.1 21.5 30.68 29.88
    Lapatinib 57.4 49.8 7.54 8.31
    aPercentage of cells inhibited by the compound concentration of 10 μmol/L was treated for 48 h；bInhibition rate of LN-229 and SCG-7901 cells reached 50%
    下载: 导出CSV
    • 参考文献(11)
  • [1]

    Wang XL, Lin FL, Xu W, et al. Silybin B exerts protective effect on cisplatin-induced neurotoxicity by alleviating DNA damage and apoptosis[J]. J Ethnopharmacol, 2022, 288: 114938. doi: 10.1016/j.jep.2021.114938
    [2] Hu L, Tong H, Ding R, et al. Absorption mechanism of silybin in human intestinal Caco-2 cells[J]. J China Pharm Univ (中国药科大学学报), 2018, 49(2): 202-208.
    [3]

    Liu YY, Xu W, Zhai T, et al. Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway[J]. Acta Pharm Sin B, 2019, 9(4): 745-757. doi: 10.1016/j.apsb.2019.02.006
    [4]

    Wesołowska O, Łania-Pietrzak B, Kuzdzał M, et al. Influence of silybin on biophysical properties of phospholipid bilayers[J]. Acta Pharmacol Sin, 2007, 28(2): 296-306. doi: 10.1111/j.1745-7254.2007.00487.x
    [5]

    Bijak M. Silybin, a major bioactive component of milk thistle (Silybum marianum L. gaernt. )-chemistry, bioavailability, and metabolism[J]. Molecules, 2017, 22(11): 1942. doi: 10.3390/molecules22111942
    [6]

    Verdura S, Encinar JA, Teixidor E, et al. Silibinin overcomes EMT-driven lung cancer resistance to new-generation ALK inhibitors[J]. Cancers, 2022, 14(24): 6101. doi: 10.3390/cancers14246101
    [7]

    Wei ZB, Ye SY, Feng HP, et al. Silybin suppresses ovarian cancer cell proliferation by inhibiting isocitrate dehydrogenase 1 activity[J]. Cancer Sci, 2022, 113(9): 3032-3043. doi: 10.1111/cas.15470
    [8]

    Colturato CP, Constantin RP, Maeda AS Jr, et al. Metabolic effects of silibinin in the rat liver[J]. Chem Biol Interact, 2012, 195(2): 119-132. doi: 10.1016/j.cbi.2011.11.006
    [9]

    Haddad Y, Vallerand D, Brault A, et al. Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis[J]. Evid Based Complement Alternat Med, 2011, 2011: nep164.
    [10]

    Krecman V, Skottová N, Walterová D, et al. Silymarin inhibits the development of diet-induced hypercholesterolemia in rats[J]. Planta Med, 1998, 64(2): 138-142. doi: 10.1055/s-2006-957391
    [11] Sun TM, Li X. Synthesis of 2, 3-dehydrosilymarin[J]. Chin J Pharm Chem(中国药物化学杂志), 2000, 10(2): 40-41.
    • 相关文章
    • 施引文献
    • 资源附件(0)
图(1)  /  表(3)
计量
  • 文章访问数:  29
  • HTML全文浏览量:  11
  • PDF下载量:  24
  • 被引次数: 0
出版历程
  • 收稿日期:  2024-04-16
  • 修回日期:  2024-05-13
  • 录用日期:  2024-05-21
  • 刊出日期:  2025-06-24

目录

摘要
HTML全文
    参考文献(11)
    相关文章
    施引文献
    资源附件(0)

    /

    返回文章
    返回

    版权所有：《中国药科大学学报》编辑部苏ICP备05007142号

    地址：江苏省南京市鼓楼区童家巷24号（210009）电话: 025-83271566E-mail: xuebao@cpu.edu.cn

    本系统由 北京仁和汇智信息技术有限公司 开发  百度统计

    访问量：453265

    x 关闭 永久关闭