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2020 , Vol. 40 >Issue 4: 978 - 987

DOI: https://doi.org/10.6023/cjoc201909016

研究论文

新型三甲氧基苯基喹啉衍生物的设计、合成及抗肿瘤活性研究

  • 吴博文 ,
  • 崔鑫鑫 ,
  • 朱挺 ,
  • 王胜辉 ,
  • 陆超凡 ,
  • 王金杰 ,
  • 党贺祥 ,
  • 张赛扬 ,
  • 丁丽娜 ,
  • 金成允
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  • a 新药创制与药物安全性评价河南省协同创新中心 郑州 450001;
    b 郑州大学基础医学院 郑州 450001;
    c 教育部药物制备关键技术重点实验室 郑州 450001;
    d 郑州大学河南省先进技术研究院 郑州 450001

收稿日期: 2019-09-10

  修回日期: 2019-11-21

  网络出版日期: 2020-05-06

基金资助

国家自然科学基金（Nos.81703541，81673322）和中国博士后科学基金（No.2018M632812）资助项目.

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Design, Synthesis and Anticancer Activity Studies of Novel Trimethoxyphenyl-quinoline Derivatives

  • Wu Bowen ,
  • Cui Xinxin ,
  • Zhu Ting ,
  • Wang Shenghui ,
  • Lu Chaofan ,
  • Wang Jinjie ,
  • Dang Hexiang ,
  • Zhang Saiyang ,
  • Ding Li'na ,
  • Jin Chengyun
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  • a Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou 450001;
    b School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001;
    c Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001;
    c Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001

Received date: 2019-09-10

  Revised date: 2019-11-21

  Online published: 2020-05-06

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 81703541, 81673322) and the China Postdoctoral Science Foundation (No. 2018M632812).

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摘要

为了寻找新型高效抗肿瘤候选药物，设计并合成了一系列新型三甲氧基苯基-喹啉杂合体，并评估了目标化合物对三种不同肿瘤细胞EC-109（人食管癌细胞），PC-3（人前列腺癌细胞）和MGC-803（人胃癌细胞）的抗增殖活性.结果表明N-（3-（氯甲基）苄基）-3，4，5-三甲氧基-N-（喹啉-8-基）苯甲酰胺（12j）对PC-3细胞具有良好的抗增殖活性，IC50值为9.23 μmol/L.同时，化合物12j抑制PC-3细胞增殖和克隆形成.进一步机制研究表明，化合物12j可以将PC-3细胞阻滞在G2/M期，并通过激活内源性和外源性凋亡途径诱导细胞凋亡.

关键词： 喹啉; 三甲氧基苯基; 抗肿瘤活性; 细胞周期阻滞; 凋亡

本文引用格式

吴博文 , 崔鑫鑫 , 朱挺 , 王胜辉 , 陆超凡 , 王金杰 , 党贺祥 , 张赛扬 , 丁丽娜 , 金成允 . 新型三甲氧基苯基喹啉衍生物的设计、合成及抗肿瘤活性研究[J]. 有机化学, 2020 , 40(4) : 978 -987 . DOI: 10.6023/cjoc201909016

Abstract

With the expectation to find out novel and effective anti-tumor agents, a series of novel trimethoxyphenyl-quinoline hybrids were designed, synthesized and evaluated for antiproliferative activity against three human cancer cell lines (EC-109, human esophageal cancer cells; PC-3, human prostate cancer cells; MGC-803, human gastric cancer cells). N-(3-(Chloromethyl)benzyl)-3,4,5-trimethoxy-N-(quinolin-8-yl)benzamide (12j) showed the most potent antitumor activity against PC-3 cells with IC50 value of 9.23 μmol/L. Meanwhile, compound 12j inhibited the cell viability and colony formation of PC-3 cells. Further mechanism studies revealed that compound 12j could arrest PC-3 cells in G2/M phase and induce cell apoptosis via activating intrinsic and extrinsic apoptosis pathway.

Key words： quinoline; trimethoxyphenyl; anticancer; cell cycle arrest; apoptosis

参考文献

[1] Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. Ca-Cancer J. Clin. 2018, 68, 394.
[2] Zhu, S.-L.; Wu, Y.; Liu, C.-J.; Wei, C.-Y.; Tao, J.-C.; Liu, H.-M. Eur. J. Med. Chem. 2013, 65, 70.
[3] Saraswati, A. P.; Relitti, N.; Brindisi, M.; Gemma, S.; Zisterer, D.; Butini, S.; Campiani, G. Drug Discovery Today 2019, 24, 1370.
[4] Afzal, O.; Kumar, S.; Haider, M. R.; Ali, M. R.; Kumar, R.; Jaggi, M.; Bawa, S. Eur. J. Med. Chem. 2015, 97, 871.
[5] Hamdy, R.; Elseginy, S.; Ziedan, N.; Jones, A.; Westwell, A. Molecules 2019, 24, 1274.
[6] Mrozek-Wilczkiewicz, A.; Malarz, K.; Rejmund, M.; Polanski, J.; Musiol, R. Eur. J. Med. Chem. 2019, 171, 180.
[7] Shen, C.; Xu, J.; Xia, C.; Yang, Y.; Shen, H.; Ying, B.; Zhu, X. Zhang, P. Science 2018, 360, 20.
[8] El-Gamal, K. M.; El-Morsy, A. M.; Saad, A. M.; Eissa, I. H.; Alswah, M. J. Mol. Struct. 2018, 1166, 15.
[9] Akash, B.; Yasmeen, A.; Young, S. K.; Verrill, M. N.; Shouguang, J.; Robert, W. H. Eur. J. Med. Chem. 2018, 155, 705.
[10] Pankaj, W.; Priti, J.; Santosh, R.; Hemant, R. A. J. Curr. Drug Discovery Technol. 2018, 15, 2.
[11] Chokkar, N.; Kalra, S.; Chauhan, M.; Kumar, R. Mini-Rev. Med. Chem. 2019, 19, 510.
[12] Hosseinzadeh, H.; Mazaheri, F.; Ghodsi, R. Iran J. Basic Med. Sci. 2017, 20, 446.
[13] Han, B.; Li, K.; Zhao, Y.; Li, B.; Cheng, Y.; Zhou, J.; Lu, Y.; Shi, Y.; Wang, Z.; Jiang, L. Br. J. Cancer 2018, 118, 654.
[14] Vaishampayan, U. N.; Podgorski, I.; Heilbrun, L. K.; Lawhorn-Crews, J. M.; Dobson, K. C.; Boerner, J.; Stark, K.; Smith, D. W.; Heath, E. I.; Fontana, J. A. Clin. Cancer Res. 2019, 25, 652.
[15] Zhu, X.-F.; Zhang, J.; Sun, S.; Guo, Y.-C.; Cao, S.-X.; Zhao, Y.-F. Chin. Chem. Lett. 2017, 28, 1514.
[16] Yang, H.; Qi, H.; Liu, T.; Shao, X.; Yang, Q.; Qian, X. Chin. Chem. Lett. 2019, 30, 977.
[17] Yang, Y.; Guo, J.; Liu, Z.-Z. Chin. J. Org. Chem. 2019, 39, 1913(in Chinese). (杨扬, 郭举, 刘站柱, 有机化学, 2019, 39, 1913.)
[18] Hu, Y.; Li, Z.-Y.; Ding, Y.-J.; Li, Z.-Y.; Shen, Y.-M. Chin. J. Org. Chem. 2019, 39, 3230 (in Chinese). (胡园, 李震宇, 丁艳娇, 李志颖, 刘志勇, 沈月毛, 有机化学, 2019, 39, 3230.)
[19] Li, Z.-Y.; Ding, Y.-J.; Bu, H.-G.; Shen, Y.-M. Chin. J. Org. Chem. 2018, 38, 3204(in Chinese). (李志颖, 丁艳娇, 卜华港, 沈月毛, 有机化学, 2018, 38, 3204.)
[20] Okten, S.; Cakmak, O.; Tekin, S.; Koprulu, T. K. Lett. Drug Des. Discovery 2017, 14, 1415.
[21] Yang, W.; Dolloff, N. G.; El-Deiry, W. S. Nat. Cell Biol. 2008, 10, 125.
[22] Ganesh, T.; Min, J.; Thepchatri, P.; Du, Y.; Li, L.; Lewis, I.; Wilson, L.; Fu, H.; Chiosis, G.; Dingledine, R. Bioorg. Med. Chem. Lett. 2008, 16, 6903.
[23] Lo, Y.-H.; Lin, Y.-T.; Liu, Y.-P.; Duh, T.-H.; Lu, P.-J.; Wu, M.-J. Eur. J. Med. Chem. 2013, 62, 526.
[24] Pingaew, R.; Saekee, A.; Mandi, P.; Nantasenamat, C.; Prachaya-sittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Eur. J. Med. Chem. 2014, 85, 65.
[25] Romagnoli, R.; Baraldi, P. G.; Kimatrai Salvador, M.; Preti, D.; Aghazadeh Tabrizi, M.; Bassetto, M.; Brancale, A.; Hamel, E.; Castagliuolo, I.; Bortolozzi, R. J. Med. Chem. 2013, 56, 2606.
[26] Vitale, I.; Antoccia, A.; Cenciarelli, C.; Crateri, P.; Meschini, S.; Arancia, G.; Pisano, C.; Tanzarella, C. Apoptosis 2007, 12, 155.
[27] Wang, L.; Liu, S.; Wang, L.; Yan, P.; Wang, J.; Zhang, J.; Guo, H.; Guan, Q.; Bao, K.; Wu,Y. Eur. J. Med. Chem. 2018, 156, 137.
[28] Yan, J.; Chen, J.; Zhang, S.; Hu, J.; Huang, L.; Li, X. J. Med. Chem. 2016, 59, 5264.
[29] ElHady, A. K.; Abdel-Halim, M.; Abadi, A. H.; Engel, M. J. Med. Chem. 2017, 60, 5377.
[30] Hammill, J. T.; Bhasin, D.; Scott, D. C.; Min, J.; Chen, Y.; Lu, Y.; Yang, L.; Kim, H. S.; Connelly, M. C.; Hammill, C. J. Med. Chem. 2018, 61, 2694.
[31] Fu, D.-J.; Fu, L.; Liu, Y.-C.; Wang, J.-W.; Wang, Y.-Q.; Han, B.-K.; Li, X.-R.; Zhang, C.; Li, F.; Song, J. Sci. Rep. 2017, 7, 12788.
[32] Fu, D.-J.; Li, P.; Wu, B.-W.; Cui, X.-X.; Zhao, C.-B.; Zhang, S.-Y. Eur. J. Med. Chem. 2019, 165, 309.
[33] Fu, D.-J.; Yang, J.-J.; Li, P.; Hou, Y.-H.; Huang, S.-N.; Tippin, M. A.; Pham, V.; Song, L.; Zi, X.; Xue, W.-L. Eur. J. Med. Chem. 2018, 157, 50.
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