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

LUO Chunxia; ZHU Li; LI Xinyu; AMET Mutallip; NIJIATI Yiliyaer; LI Xinxia; GUAN Ming

doi:10.11665/j.issn.1000-5048.20190613

Journal of China Pharmaceutical University > 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:

PDF (2928 KB)

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

More Information

Graphical Abstract

Abstract

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.
- folic acid-alliinase conjugate,
- coupling ratio,
- targeting,
- antitumor activity,
- HeLa cells

FullText(HTML)

References (18)

References

[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.

[1]	CHU Xuxin, BU Fanxue, YIN Tingjie, HUO Meirong. Antitumor strategies based on targeted modulation of tumor-associated macrophages[J]. Journal of China Pharmaceutical University, 2021, 52(3): 261-269. DOI: 10.11665/j.issn.1000-5048.20210301
[2]	HAN Chun, WU Lintao, HU Xiaoqin, SUN Long, HUANG Zhangjian, ZHANG Yihua. Design, synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates[J]. Journal of China Pharmaceutical University, 2018, 49(1): 48-55. DOI: 10.11665/j.issn.1000-5048.20180107
[3]	ZHAO Yuekui, TANG Shanshan, ZHANG Yanfeng, ZONG Li, JIN Liang. Engineered mesenchymal stem cells as targeting therapeutic carriers in cancer therapy[J]. Journal of China Pharmaceutical University, 2016, 47(2): 134-139. DOI: 10.11665/j.issn.1000-5048.20160202
[4]	ZHANG Zhiqing, WANG Fang, ZHOU Ting, ZHANG Guodong, WANG Xiufeng, LI Yunze. A DNA polyaptamer system as a targeted antitumor drug delivery[J]. Journal of China Pharmaceutical University, 2015, 46(4). DOI: 10.11665/j.issn.1000-5048.20150408
[5]	MAO Chunfang, XU Chenjun, WANG Xuemin, LI Xianghua, ZHANG Wei, WANG Xinyang, LING Yong. Design, synthesis and antitumor activity of farnesylthiosalicylamide derivatives[J]. Journal of China Pharmaceutical University, 2015, 46(2): 162-168. DOI: 10.11665/j.issn.1000-5048.20150204
[6]	WANG Zhiqiang, WANG Xuemin, ZHANG Wei, WANG Xinyang, LING Yong, CHEN Li. Synthesis and biological evaluation of novel farnesylthiosalicylic acid/hydro-xylcinnamic acid hybrids as potential antitumor agents[J]. Journal of China Pharmaceutical University, 2014, 45(4): 392-399. DOI: 10.11665/j.issn.1000-5048.20140402
[7]	JIN Hui, LIU Lifeng, DENG Weiping, LIU Jianwen. Antitumor effects and molecular mechanisms of novel selective HDAC inhibitors in human cervix carcinoma HeLa cells[J]. Journal of China Pharmaceutical University, 2013, 44(4): 352-356. DOI: 10.11665/j.issn.1000-5048.20130413
[8]	REN Jie, XIN Wenqun, CHEN Xin, HU Kun. Apoptosis induced by podophyllotoxin derivative OAMDP in HeLa cells[J]. Journal of China Pharmaceutical University, 2013, 44(3): 267-271. DOI: 10.11665/j.issn.1000-5048.20130316
[9]	Transcription factors as new targets for cancer therapy[J]. Journal of China Pharmaceutical University, 2010, 41(2): 97-103.
[10]	A Quickly and Simplified Method for Screening Anticancer Drug in Telomerase Activity as a Target[J]. Journal of China Pharmaceutical University, 1999, (1): 56-59.

Cited By

Cited by

Periodical cited type(2)

1.	王秋雨，李新霞，兰怡，毛新民，马红梅. 基于网络药理学和体外实验验证大蒜含硫化合物蒜氨酸抑制慢性气道炎症的作用机制研究. 中南药学. 2023(05): 1170-1176 .
2.	陈晓东，沈衡平，付文婷，曾素雯，杨安平，刘辉. 高效液相色谱法测定化妆品中蒜氨酸含量. 广东化工. 2020(19): 151-152 .

Other cited types(0)

Get Citation

PDF

XML

Article views (515) PDF downloads (609) Cited by(2)

Turn off MathJax

Article Contents

Abstract

References

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

Abstract

References

Related Articles

Cited by

Periodical cited type(2)

Other cited types(0)

Catalog

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

Abstract

References

Related Articles

Cited by

Periodical cited type(2)

Other cited types(0)

Catalog

Export File

Citation

Format

Content