Citation: Zhang Yang, Zhang Luye, Liu Limin, Wang Tao, Meng Yaqi, Li Na, Li Erdong, Wang Zhengjie, Liu Xiujuan, Zheng Jiaxin, Shan Lihong, Liu Hongmin, Zhang Qiurong. Synthesis and Antitumor Activity Evaluation of Novel Hydrazone-Substituted Pyrimidine Derivatives[J]. Chinese Journal of Organic Chemistry, ;2020, 40(6): 1731-1736. doi: 10.6023/cjoc202001034 shu

Synthesis and Antitumor Activity Evaluation of Novel Hydrazone-Substituted Pyrimidine Derivatives

Zhang Yang ^a,b ,
Zhang Luye ^a,b ,
Liu Limin ^a,b ,
Wang Tao ^a,b ,
Meng Yaqi ^a,b ,
Li Na ^a,b ,
Li Erdong ^a,b ,
Wang Zhengjie ^a,b ,
Liu Xiujuan ^a,b ,
Zheng Jiaxin ^a,c ,
Shan Lihong ^a,b,c,d,, ,
Liu Hongmin ^a,b,c,d,e,, ,
Zhang Qiurong ^a,b,c,d,,

a.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
c.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001
d.
Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001
e.
State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450052

Corresponding author: Shan Lihong, shlh@zzu.edu.cn Liu Hongmin, liuhm@zzu.edu.cn Zhang Qiurong, zqr409@yeah.net
Received Date: 31 January 2020
Revised Date: 21 March 2020
Available Online: 10 April 2020
Fund Project: the National Key Research Program of Proteins 2018YFE0195100the National Natural Science Foundation of China 81773562Project supported by the National Natural Science Foundation of China (No. 81773562) and the National Key Research Program of Proteins (No. 2018YFE0195100) and the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X)the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment K2020000X

Figures(2)

In order to find more effective antitumor drugs, a series of novel hydrazone-substituted pyrimidine derivatives were designed, synthesized and evaluated for their antitumor activity against five different human cancer cell lines including MCF-7 (human breast cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell), Hela (human cervical cancer cell) and A549 (human lung cancer cell) using methyl thiazolyl tetrazolium (MTT) assay. Most of the target compounds showed moderate to potent antitumor activity against five selected cancer cell lines. Among them, 2-(prop-2-yn-1-ylthio)-4-(2-(pyridin-2-ylmethylene)-hydrazinyl)-6-(trifluoromethyl)pyrimidine (12l) displayed the most potent anti-proliferative activity against PC-3 cell line (IC₅₀ = 1.37 μmol·L^-1), which was significantly better than the positive control drug 5-fluorouracil. This work provided clues to discover new antitumor agents.
- hydrazone,
- pyrimidine derivatives,
- synthesis,
- antitumor activity
1. [1]
  Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. CA Cancer J. Clin. 2018, 68, 394. doi: 10.3322/caac.21492
2. [2]
  Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D. M.; Pineros, M.; Znaor, A.; Bray, F. Int. J. Cancer 2019, 144, 1941. doi: 10.1002/ijc.31937
3. [3]
  Lavi, O.; Gottesman, M. M.; Levy, D. Drug Resist. Updates 2012, 15, 90. doi: 10.1016/j.drup.2012.01.003
4. [4]
  Li, E. D.; Lin, Q.; Meng, Y. Q.; Zhang, L. Y.; Song, P. P.; Li, N.; Xin, J. C.; Yang, P.; Bao, C. N.; Zhang, D. Q.; Zhang, Y.; Wang, J. K.; Zhang, Q. R.; Liu, H. M. Eur. J. Med. Chem. 2019, 172, 36. doi: 10.1016/j.ejmech.2019.03.030
5. [5]
  Meng, Y.; Li, E.; Zhang, Y.; Liu, S.; Bao, C.; Yang, P.; Zhang, L.; Zhang, D.; Wang, J.; Chen, Y.; Li, N.; Xin, J.; Zhao, P.; Ke, Y.; Zhang, Q.; Liu, H. Chin. J. Org. Chem 2019, 39, 2541(in Chinese).
6. [6]
  Keche, A. P.; Hatnapure, G. D.; Tale, R. H.; Rodge, A. H.; Birajdar, S. S.; Kamble, V. M. Bioorg. Med. Chem. Lett. 2012, 22, 3445. doi: 10.1016/j.bmcl.2012.03.092
7. [7]
  Shakya, N.; Vedi, S.; Liang, C.; Yang, F.; Agrawal, B.; Kumar, R. Bioorg. Med. Chem. Lett. 2014, 24, 1407. doi: 10.1016/j.bmcl.2014.01.024
8. [8]
  Yang, Z.; Fang, Y.; Pham, T. A.; Lee, J.; Park, H. Bioorg. Med. Chem. Lett. 2013, 23, 1519. doi: 10.1016/j.bmcl.2012.12.011
9. [9]
  Mantipally, M.; Gangireddy, M. R.; Gundla, R.; Badavath, V. N.; Mandha, S. R.; Maddipati, V. C. Bioorg. Med. Chem. Lett. 2019, 29, 2248. doi: 10.1016/j.bmcl.2019.06.031
10. [10]
  Pouremad, R.; Bahk, K. D.; Shen, Y. J.; Knop, R. H.; Wyrwicz, A. M. NMR Biomed. 1999, 12, 373. doi: 10.1002/(SICI)1099-1492(199910)12:6<373::AID-NBM569>3.0.CO;2-R
11. [11]
  Xin, M.; Wen, J.; Tang, F.; Tu, C.; Huang, W.; Shen, H.; Zhao, X.; Cheng, L.; Wang, M.; Zhang, L. Bioorg. Med. Chem. Lett. 2014, 24, 983. doi: 10.1016/j.bmcl.2013.12.050
12. [12]
  Gabr, M. T.; El-Gohary, N. S.; El-Bendary, E. R.; El-Kerdawy, M. M.; Ni, N. Chin. Chem. Lett. 2016, 27, 380.
13. [13]
  Nartop, D.; Özkan, E. H.; Gündem, M.; Çeker, S.; Ağar, G.; Öğütcü, H.; Sarı, N. J. Mol. Struct. 2019, 1195, 877. doi: 10.1016/j.molstruc.2019.06.042
14. [14]
  Rakesh, K. P.; Kumara, H. K.; Ullas, B. J.; Shivakumara, J.; Channe Gowda, D. Bioorg. Chem. 2019, 90, 103093. doi: 10.1016/j.bioorg.2019.103093
15. [15]
  Alafeefy, A. M.; Bakht, M. A.; Ganaie, M. A.; Ansarie, M. N.; El-Sayed, N. N.; Awaad, A. S. Bioorg. Med. Chem. Lett. 2015, 25, 179. doi: 10.1016/j.bmcl.2014.11.088
16. [16]
  Wang, Y. Y.; Xu, F. Z.; Zhu, Y. Y.; Song, B.; Luo, D.; Yu, G.; Chen, S.; Xue, W.; Wu, J. Bioorg. Med. Chem. Lett. 2018, 28, 2979. doi: 10.1016/j.bmcl.2018.06.049
17. [17]
  Kumar, K. S.; Ganguly, S.; Veerasamy, R.; De Clercq, E. Eur. J. Med. Chem. 2010, 45, 5474.
18. [18]
  Saadaoui, I.; Krichen, F.; Ben Salah, B.; Ben Mansour, R.; Miled, N.; Bougatef, A.; Kossentini, M. J. Mol. Struct. 2019, 1180, 344. doi: 10.1016/j.molstruc.2018.12.008
19. [19]
  Yahaya, I.; Chemchem, M.; Aydıner, B.; Seferoğlu, N.; Erva Tepe, F.; Açık, L.; Aytuna Çerçi, N.; Türk, M.; Seferoğlu, Z. J. Photochem. Photobiol., A 2019, 368, 296. doi: 10.1016/j.jphotochem.2018.09.041
20. [20]
  Peng, X.; Liu, P.; Pang, B.; Yao, Y.; Wang, J.; Zhang, K. Carbohydr. Polym. 2019, 216, 113. doi: 10.1016/j.carbpol.2019.04.029
21. [21]
  Abdel-Mohsen, H. T.; Conrad, J.; Harms, K.; Nohr, D.; Beifuss, U. RSC Adv. 2017, 7, 17427. doi: 10.1039/C6RA28102H
22. [22]
  Minn, K.; Braun, P.; Sachse, B.; Wicke, H. DE 4029648, 1992.
1. [1]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
2. [2]
  Maitri Bhattacharjee , Rekha Boruah Smriti , R. N. Dutta Purkayastha , Waldemar Maniukiewicz , Shubhamoy Chowdhury , Debasish Maiti , Tamanna Akhtar . Synthesis, structural characterization, bio-activity, and density functional theory calculation on Cu(Ⅱ) complexes with hydrazone-based Schiff base ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1409-1422. doi: 10.11862/CJIC.20240007
3. [3]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
4. [4]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
5. [5]
  Bofei JIA , Zhihao LIU , Zongyuan GAO , Shuai ZHOU , Mengxiang WU , Qian ZHANG , Xiamei ZHANG , Shuzhong CHEN , Xiaohan YANG , Yahong LI . Cu(Ⅱ) and Cu(Ⅰ) complexes based on derivatives of imidazo[1,5-a]pyridine: Synthesis, structures, in situ metal-ligand reactions, and catalytic activity. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 1020-1036. doi: 10.11862/CJIC.20240317
6. [6]
  Di ZHANG , Tianxiang XIE , Xu HE , Wanyu WEI , Qi FAN , Jie QIAO , Gang JIN , Ningbo LI . Construction and antitumor activity of pH/GSH dual-responsive magnetic nanodrug. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 786-796. doi: 10.11862/CJIC.20240329
7. [7]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
8. [8]
  Fengqing Wang , Changxing Qi , Chunmei Chen , Qin Li , Qingyi Tong , Weiguang Sun , Zhengxi Hu , Minyan Wang , Hucheng Zhu , Lianghu Gu , Yonghui Zhang . Discovery and enantioselective total synthesis of antitumor agent asperfilasin A via a regio- and diastereoselective Nazarov cyclization. Chinese Chemical Letters, 2025, 36(6): 110252-. doi: 10.1016/j.cclet.2024.110252
9. [9]
  Hong-Tao Ji , Yu-Han Lu , Yan-Ting Liu , Yu-Lin Huang , Jiang-Feng Tian , Feng Liu , Yan-Yan Zeng , Hai-Yan Yang , Yong-Hong Zhang , Wei-Min He . Nd@C₃N₄-photoredox/chlorine dual catalyzed synthesis and evaluation of antitumor activities of 4-alkylated sulfonyl ketimines. Chinese Chemical Letters, 2025, 36(2): 110568-. doi: 10.1016/j.cclet.2024.110568
10. [10]
  Shuying Li , Weiwei ZhuGe , Xuan Sun , Chongzhen Sun , Zhaojun Liu , Chenghe Xiong , Min Xiao , Guofeng Gu . Convergent synthesis and immunological study of oligosaccharide derivatives related to galactomannan from Antrodia cinnamomea. Chinese Chemical Letters, 2024, 35(5): 109089-. doi: 10.1016/j.cclet.2023.109089
11. [11]
  Shushan Mo , Zhaoshuo Wang , Dandan Ding , Zhengzheng Yan , Yunlu Dai , Jinchao Zhang , Huifang Liu , Tianjiao Liang , Jianfei Tong , Zhenhua Li , Xueyi Wang . The synthesis and evaluation of novel BPA derivatives for enhanced blood-brain barrier penetration and boron neutron capture therapy. Chinese Chemical Letters, 2025, 36(5): 110190-. doi: 10.1016/j.cclet.2024.110190
12. [12]
  Anqiu LIU , Long LIN , Dezhi ZHANG , Junyu LEI , Kefeng WANG , Wei ZHANG , Junpeng ZHUANG , Haijun HAO . Synthesis, structures, and catalytic activity of aluminum and zinc complexes chelated by 2-((2,6-dimethylphenyl)amino)ethanolate. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 791-798. doi: 10.11862/CJIC.20230424
13. [13]
  Guoping Yang , Zhoufu Lin , Xize Zhang , Jiawei Cao , Xuejiao Chen , Yufeng Liu , Xiaoling Lin , Ke Li . Assembly of Y(Ⅲ)-containing antimonotungstates induced by malic acid with catalytic activity for the synthesis of imidazoles. Chinese Chemical Letters, 2024, 35(12): 110274-. doi: 10.1016/j.cclet.2024.110274
14. [14]
  Yao HUANG , Yingshu WU , Zhichun BAO , Yue HUANG , Shangfeng TANG , Ruixue LIU , Yancheng LIU , Hong LIANG . Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359
15. [15]
  Zhiwei Chen , Heyun Sheng , Xue Li , Menghan Chen , Xin Li , Qiuling Song . Efficient capture of difluorocarbene by pyridinium 1,4-zwitterionic thiolates: A concise synthesis of difluoromethylene-containing 1,4-thiazine derivatives. Chinese Chemical Letters, 2024, 35(4): 108937-. doi: 10.1016/j.cclet.2023.108937
16. [16]
  Jian Song , Shenghui Wang , Qiuge Liu , Xiao Wang , Shuo Yuan , Hongmin Liu , Saiyang Zhang . N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers: Design, structure–activity relationships and biological evaluations. Chinese Chemical Letters, 2025, 36(2): 109678-. doi: 10.1016/j.cclet.2024.109678
17. [17]
  Xiaomeng Hu , Jie Yu , Lijie Sun , Linfeng Zhang , Wei Zhou , Dongpeng Yan , Xinrui Wang . Synthesis of an AVB@ZnTi-LDH composite with synergistically enhance UV blocking activity and high stability for potential application in sunscreen formulations. Chinese Chemical Letters, 2024, 35(11): 109466-. doi: 10.1016/j.cclet.2023.109466
18. [18]
  Ao Sun , Zipeng Li , Shuchun Li , Xiangbao Meng , Zhongtang Li , Zhongjun Li . Stereoselective synthesis of α-3-deoxy-D-manno-oct-2-ulosonic acid (α-Kdo) derivatives using a C3-p-tolylthio-substituted Kdo fluoride donor. Chinese Chemical Letters, 2025, 36(3): 109972-. doi: 10.1016/j.cclet.2024.109972
19. [19]
  Ping Sun , Yuanqin Huang , Shunhong Chen , Xining Ma , Zhaokai Yang , Jian Wu . Indole derivatives as agrochemicals: An overview. Chinese Chemical Letters, 2024, 35(7): 109005-. doi: 10.1016/j.cclet.2023.109005
20. [20]
  Huimin Luan , Qinming Wu , Jianping Wu , Xiangju Meng , Feng-Shou Xiao . Templates for the synthesis of zeolites. Chinese Journal of Structural Chemistry, 2024, 43(4): 100252-100252. doi: 10.1016/j.cjsc.2024.100252

Get Citation

PDF

XML

Metrics

PDF Downloads(12)
Abstract views(787)
HTML views(145)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142