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叶酸-蒜酶缀合物的合成及联合蒜氨酸原位抑制肿瘤细胞增殖作用

罗春霞, 朱丽, 李心雨, 木塔力甫·艾买提, 伊力亚尔·尼加提, 李新霞, 关明

罗春霞, 朱丽, 李心雨, 木塔力甫·艾买提, 伊力亚尔·尼加提, 李新霞, 关明. 叶酸-蒜酶缀合物的合成及联合蒜氨酸原位抑制肿瘤细胞增殖作用[J]. 中国药科大学学报, 2019, 50(6): 721-727. DOI: 10.11665/j.issn.1000-5048.20190613
引用本文: 罗春霞, 朱丽, 李心雨, 木塔力甫·艾买提, 伊力亚尔·尼加提, 李新霞, 关明. 叶酸-蒜酶缀合物的合成及联合蒜氨酸原位抑制肿瘤细胞增殖作用[J]. 中国药科大学学报, 2019, 50(6): 721-727. DOI: 10.11665/j.issn.1000-5048.20190613
LUO Chunxia, ZHU Li, LI Xinyu, AMET Mutallip, NIJIATI Yiliyaer, LI Xinxia, GUAN Ming. Synthesis of folic acid-alliinase conjugate and its in situ inhibition of tumor cell proliferation by combination of alliin[J]. Journal of China Pharmaceutical University, 2019, 50(6): 721-727. DOI: 10.11665/j.issn.1000-5048.20190613
Citation: LUO Chunxia, ZHU Li, LI Xinyu, AMET Mutallip, NIJIATI Yiliyaer, LI Xinxia, GUAN Ming. Synthesis of folic acid-alliinase conjugate and its in situ inhibition of tumor cell proliferation by combination of alliin[J]. Journal of China Pharmaceutical University, 2019, 50(6): 721-727. DOI: 10.11665/j.issn.1000-5048.20190613

叶酸-蒜酶缀合物的合成及联合蒜氨酸原位抑制肿瘤细胞增殖作用

基金项目: 新疆维吾尔自治区联合基金资助项目(No.2016D01C157) #罗春霞和朱丽对本论文的贡献相同

Synthesis of folic acid-alliinase conjugate and its in situ inhibition of tumor cell proliferation by combination of alliin

  • 摘要: 合成叶酸-蒜酶缀合物(FA-Alliinase),采用宫颈癌HeLa细胞考察其对肿瘤细胞的靶向性和抑制肿瘤生长活性。采用两种方法合成叶酸-蒜酶缀合物FA-AlliinaseⅠ和FA-AlliinaseⅡ,测得两种缀合物的偶联比分别为12和31,选择高偶联比的FA-AlliinaseⅡ,对其结构进行初步的表征。高效液相色谱法测得FA-AlliinaseⅡ有约50%的蒜酶活力;激光共聚焦及流式细胞仪观察到FA-AlliinaseⅡ对HeLa细胞具有一定的靶向性,MTT法测得FA-AlliinaseⅡ联合蒜氨酸后对HeLa细胞增殖有抑制作用,以蒜氨酸计IC50为(127.6±2.3)μmol/L。该研究为类前药叶酸-蒜酶缀合物的合成优化提供了较为直接的评价方法。
    Abstract: To synthesize the folic acid-alliinase conjugate(FA-Alliinase), and to study its targeting and antitumor activity on cervical cancer HeLa cells. FA-Alliinase I and FA-Alliinase II were synthesized by two methods. The couping ratios of two conjugates measured were 12 and 31, respectively. The FA-Alliinase II with high coupling ratio was selected and its structure was characterized preliminarily. The activity of alliinase retained about 50% in FA-Alliinase II determined by HPLC. The specific effect of FA-Alliinase II on HeLa cells was observed by confocal laser and flow cytometry. The antitumor activity of conjugate combined with alliin was determined by MTT, and IC50 of alliin was(127. 6±2. 3)μmol/L. This study provides a direct evaluation method for the synthesis and optimization of FA-Alliinase.
  • [1] Borlinghaus J,Albrecht F,Gruhlke MC,et al.Allicin:chemistry and biological properties[J].Molecules,2014,19(8):12591-12618.
    [2] Lin SF,Li XX,Lang LW,et al.Ratio of alliin/alliinase in catalytic system of garlic[J].J China Pharm Univ(中国药科大学学报),2010,41(3):231-234.
    [3] Stoll A,Seebeck E.Chemical investigations on alliin,the specific principle of garlic[J].Adv Enzymol Relat Areas Mol Biol,1951,11(11):377-400.
    [4] Lanzotti V,Scala F,Bonanomi G.Compounds from allium species with cytotoxic and antimicrobial activity[J].Phytochem Rev,2014,13(4):769-791.
    [5] Chhabria SV,Akbarsha MA,Li AP,et al.In situ allicin generation using targeted alliinase delivery for inhibition of MIA PaCa-2 cells via epigenetic changes,oxidative stress and cyclin-dependent kinase inhibitor(CDKI)expression[J].Apoptosis,2015,20(10):1388-1409.
    [6] Li JF.Pharmacokinetics garlic sulfur compounds and correlation with H2S Effect(大蒜含硫化合物药动学及与H2S作用的相关性研究)[D].Xinjiang:Xinjiang Medical University,2016.
    [7] Miron T,Mironchik M,Mirelman D,et al.Inhibition of tumor growth by a novel approach:in situ allicin generation using targeted alliinase delivery[J].Mol Cancer Ther,2003,2(12):1295-1301.
    [8] Arditti FD,Rabinkov A,Miron T,et al.Apoptotic killing of B-chronic lymphocytic leukemia tumor cells by allicin generated in situ using a rituximab-alliinase conjugate[J].Mol Cancer Ther,2005,4(2):325-331.
    [9] Appel E, Vallon-Eberhard A, Rabinkov A, et al. Therapy of murine pulmonary aspergillosis with antibody-alliinase conjugates and alliin[J].Antimicrob Agents Chemother,2010,54(2):898-906.
    [10] Appel E,Rabinkov A,Neeman M,et al.Conjugates of daidzein-alliinase as a targeted pro-drug enzyme system against ovarian carcinoma[J].J Drug Target,2011,19(5):326-335.
    [11] Fernandez M,Javaid F,Chudasama V.Advances in targeting the folate receptor in the treatment/imaging of cancers[J].Chem Sci,2017,9(4):790-810.
    [12] Chu SY,Sun WL,Zhang GX,et al.Preparation and in vitro and in vivo evaluation of folate-BSA-coated cationic nanostructure lipid carriers [J].J China Pharm Univ(中国药科大学学报),2015,46(1):73-77.
    [13] Wang Y,Li XX,He YB,et al.Investigation of factors on determination of alliinase activity by HPLC[J].Chin J Biochem Pharm(中国生化药物杂志),2009,30(2):82-85.
    [14] Qu HH,Zhao Y,Wang XQ,et al.Synthesis and identification of baicalin artificial antigen[J].J Beijing U Traditio(北京中医药大学学报),2010,33(9):606-609.
    [15] Yu CF,Li M,Guo W,et al.Determination of drug antibody ratio in an antibody-drug conjugate[J].Acta Pharm Sin(药学学报),2014,49(3):363-367.
    [16] Cha JH,Choi YJ,Cha SH,et al.Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway[J].Oncol Rep,2012,28(1):41-48.
    [17] Benavides GA,Squadrito GL,Mills RW,et al.Hydrogen sulfide mediates the vasoactivity of garlic[J].Proc Natl Acad Sci U S A,2007,104(46):17977-17982.
    [18] Song BL.Study on the quality of alliin and the intracorporal process by intravenous administration in mice(大蒜蒜氨酸质量评价及小鼠静脉给药体内过程研究)[D].Xinjiang:Xinjiang Medical University,2017.
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  • 刊出日期:  2019-12-24

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