SIOC 中文
CJOG
Adv search

Chinese Journal of Organic Chemistry >

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

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

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
Expand
  • 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).

Fold

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

Cite this article

Wu Bowen , Cui Xinxin , Zhu Ting , Wang Shenghui , Lu Chaofan , Wang Jinjie , Dang Hexiang , Zhang Saiyang , Ding Li'na , Jin Chengyun . Design, Synthesis and Anticancer Activity Studies of Novel Trimethoxyphenyl-quinoline Derivatives[J]. Chinese Journal of Organic Chemistry, 2020 , 40(4) : 978 -987 . DOI: 10.6023/cjoc201909016

References

[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.
Options
Outlines

/

〈 〉