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异甜菊醇衍生物的合成及抗肿瘤活性

刘燕, 王婷婷, 陈莉

刘燕, 王婷婷, 陈莉. 异甜菊醇衍生物的合成及抗肿瘤活性[J]. 中国药科大学学报, 2016, 47(1): 48-53. DOI: 10.11665/j.issn.1000-5048.20160106
引用本文: 刘燕, 王婷婷, 陈莉. 异甜菊醇衍生物的合成及抗肿瘤活性[J]. 中国药科大学学报, 2016, 47(1): 48-53. DOI: 10.11665/j.issn.1000-5048.20160106
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LIU Yan, WANG Tingting, CHEN Li. Synthesis and antitumor activity of isosteviol derivatives[J]. Journal of China Pharmaceutical University, 2016, 47(1): 48-53. DOI: 10.11665/j.issn.1000-5048.20160106
Citation: LIU Yan, WANG Tingting, CHEN Li. Synthesis and antitumor activity of isosteviol derivatives[J]. Journal of China Pharmaceutical University, 2016, 47(1): 48-53. DOI: 10.11665/j.issn.1000-5048.20160106
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异甜菊醇衍生物的合成及抗肿瘤活性

  • 1.

    中国药科大学天然药物化学教研室

  • 2.

    镇江市药品检验所

Synthesis and antitumor activity of isosteviol derivatives

摘要

    摘要
  • 摘要: 对异甜菊醇C-环、D-环进行结构修饰与改造，同时将其C19-COOH成酯，设计并合成了 9个未见文献报道的新化合物( 5 ~ 13 )，所有目标化合物的结构均经ESI-MS，IR，1H NMR确定。采用MTT法测试了目标化合物对HCT116，Huh7，SW620及HepG2等细胞的抗肿瘤活性。初步研究结果表明，化合物 13 表现出对人结肠癌HCT116细胞具有选择性抑制作用(IC50=3.57 μmol/L)，与阳性对照舒尼替尼(sunitininb)(IC50=5.62 μmol/L)活性相当，化合物 10 对HCT116，Huh7，SW620均有较强抑制作用。
    Abstract: To explore isosteviol derivatives with more potent antitumor activity, nine novel C-ring and/or D-ring modified compounds( 5 - 13 )were designed and synthesized. The structures of the derivatives were identified by IR, 1H NMR and MS. Cytotoxicity of all the target compounds was tested by MTT method in HepG2, HCT116, Huh7 and SW620 cells, and the preliminary results showed that compound 13 exhibited a selective cytotoxicity(IC50=3. 57 μmol/L)against HCT116 cell, and was comparable to that of sunitininb(IC50=5. 62 μmol/L). Compound 10 has good inhibitory effects on HCT116, Huh7, SW620 cell lines.
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    • 参考文献(16)
  • [1] Nordentoft I, Jeppesen PB, Hong J, et al. Isosteviol increases insulin sensitivity and changes gene expression of key insulin regulatory genes and transcription factors in islets of the diabetic KKAy mouse[J].Diabetes Obes Metab,2008,10(10):939-949.
    [2] Ma J,Ma Z,Wang J,et al.Isosteviol reduces plasma glucose levels in the intravenous glucose tolerance test in Zucker diabetic fatty rats[J].Diabetes Obes Metab,2007,9(4):597-599.
    [3] Xu D,Li Y,Wang J,et al.The cardioprotective effect of isosteviol on rats with heart ischemia-reperfusion injury[J].Life Sci,2007,80(4):269-274.
    [4] Lin LH,Lee LW,Sheu SY,et al.Study on thestevioside analogues of steviolbioside steviol and isosteviol 19-alkyl amide dimers:synthesis and cytotoxic and antibacterial activity[J].Chem Pharm Bull,2004,52(9):1117-1122.
    [5] Wong KL, Lin JW, Liu JC, et al. Antiproliferative effect of isosteviol on angiotensin-II- treated rat aortic smooth muscle cells[J].Pharmacology,2006,76(4):163-169.
    [6] Wu Y,Liu CJ,Liu X,et al.Stereoselective synthesis,characterization,and antibacterial activities of novel isosteviol derivatives with D-Ring modification[J].Helv Chim Acta,2010,93(10):2052-2069.
    [7] Lohoelter C,Weckbecker M,Waldvogel SR.(-)-Isosteviol as a versatile ex-chiral-pool building block for organic chemistry[J].Eur J Org Chem,2013,2013(25):5539-5554.
    [8] Mosettig E,Beglinger U,Quitt P,et al,The absolute configuration of steviol and isosteviol[J].J Am Chem Soc,1963,85(15):2305-2309.
    [9] Dolder F,Lichti H,Mosettig E,et al.The structure and stereochemistry of steviol and isosteviol[J].J Am Chem Soc,1960,82(1):246-247.
    [10] Wu Y,Dai GF,Yang JH,et al.Stereoselective synthesis of 15- and 16-substituted isosteviol derivatives and their cytotoxic acti-vities[J].Bioorg Med Chem Lett,2009,19(6):1818-1821.
    [11] Wang TT,Liu Y,Chen L.Synthesis and cytotoxic activity of nitric oxide-releasing isosteviol derivatives[J].Bioorg Med Chem Lett,2014,24(9):2202-2205.
    [12] Wang J,Liu H.Application of nitrile in drug design[J].Chin J Org Chem(有机化学),2012,32(9):1643-1652.
    [13] Qiao YX,Mao Y,Huang ZJ,et al.Synthesis and antitumor activities of novel CDDO-Me analogues[J].J China Pharm Univ(中国药科大学学报),2015,46(1):16-27.
    [14] Zhao GS.Design,synthesis and anticancer activity of α,β-unsaturated carbonly derivatives(GSTπ抑制剂α,β-不饱和酮衍生物的设计、合成及其抗肿瘤活性研究)[D].Jinan:Shandong University,2006.
    [15] Hutt OE,Doan TL,Georg GI.Synthesis of skeletally diverse and stereochemically complex library templates derived from isosteviol and steviol[J].Org Lett,2013,15(7):1602-1605.
    [16] Liu JH,Tang J,Zhu ZF,et al.Design,synthesis,and anti-tumor activity of novel betulinic acid derivatives[J].J Asian Nat Prod Res,2014,16(1):34-42.
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  • 刊出日期:  2016-02-24

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