Citation: Song Panpan, Li Na, Cui Fei, Xin Jingchao, Zhang Xiaosong, Cao Qinpo, Wang Chaojie, Dai Wenjie, Meng Xiangchuan, Liu Meng, Chang Tonghang, Liu Qingyi, Sun Yuehonga, Ke Yu, Zhang Qiurong, Liu Hongmin. Synthesis and Antitumor Activity Evaluation of 2, 4, 6-Trisubstituted Pyrimidine Derivatives[J]. Chinese Journal of Organic Chemistry, ;2017, 37(10): 2725-2735. doi: 10.6023/cjoc201705013 shu

Synthesis and Antitumor Activity Evaluation of 2, 4, 6-Trisubstituted Pyrimidine Derivatives

Song Panpan ^a,b ,
Li Na ^a,b ,
Cui Fei ^a,b ,
Xin Jingchao ^a,b ,
Zhang Xiaosong ^a,b ,
Cao Qinpo ^a,b ,
Wang Chaojie ^a,b ,
Dai Wenjie ^a ,
Meng Xiangchuan ^a ,
Liu Meng ^a ,
Chang Tonghang ^a ,
Liu Qingyi ^a ,
Sun Yuehonga ^a ,
Ke Yu ^a,b,, ,
Zhang Qiurong ^a,b,, ,
Liu Hongmin ^a,b,,

a.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Saftry Evaluation, Zhengzhou 450001

Corresponding author: Ke Yu, ky@zzu.edu.cn Zhang Qiurong, zqr406@sina.com Liu Hongmin, liuhm@zzu.edu.cn
Received Date: 8 May 2017
Revised Date: 23 May 2017
Available Online: 7 October 2017
Fund Project: Project supported by the National Natural Science Foundation of China (No. 81430085) and the Research Project of Science and Technology Bureau of Zhengzhou City (No.141PQYJS554)the Research Project of Science and Technology Bureau of Zhengzhou City No.141PQYJS554the National Natural Science Foundation of China 81430085

Figures(3)

With the aim of obtaining potential antitumor candidates with more efficiency and more economic value. 40 2, 4, 6-trisubstituted pyrimidine derivatives bearing chalcone moiety were synthesized via cyclization, chlorination, substitution with benzoylacetate and ethylacetoacetate as the starting materials. The structures of target products were confirmed by ¹H NMR, ^I3C NMR and HRMS. 2, 4, 6-Trisubstituted pyrimidine derivatives bearing chalcone moiety were evaluated for anticancer activity on four human cancer cell lines including EC-109, MGC-803, HepG-2 and MDA-MB-231 by CCK-8 (cell counting Kit-8) assay. Among them, (E)-1-(4-((2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-6-methylpyrimidin-4-yl)amino)-phe-nyl)-3-(3, 4, 5-trimethoxyphenyl)prop-2-en-1-one (13u) were more cytotoxic against MGC-803 and MDA-MB-231 cell lines, with IC₅₀ values of 0.99 and 1.77 μmol·L^-1, respectively.
- 2, 4, 6-trisubstituted pyrimidine,
- chalcone,
- antitumor
1. [1]
  For statistical information about cancer, see:U. S. Food and Drug Administration. http://www.fda.gov/AboutFDA/ReportsManuals-Forms/Reports/ucm276385.htm.
2. [2]
  Sangthong, S.; Krusong, K.; Ngamrojanavanich, N.; Vilaivan, T.; Puthong, S.; Chandchawan, S.; Muangsin, N. Bioorg. Med. Chem. Lett. 2011, 21, 4813. doi: 10.1016/j.bmcl.2011.06.052
3. [3]
  Cao, R. H.; Fan, W. X.; Guo, L.; Ma, Q.; Zhang, G. X.; Li, J. R.; Chen, X. M.; Ren, Z. H.; Qiu, L. Q. Eur. J. Med. Chem. 2013, 60, 135. doi: 10.1016/j.ejmech.2012.11.045
4. [4]
  Kamal, A.; Tamboli, J. R.; Nayak, V. L.; Adil, S. F.; Vish-nuvardhan, M. V. P. S.; Ramakrishna, S. Bioorg. Med. Chem. Lett. 2013, 23, 3208. doi: 10.1016/j.bmcl.2013.03.129
5. [5]
  Kamal, A.; Dastagiri, D.; Ramaiah, M. J.; Reddy, J. S.; Bharathi, E. V.; Reddy, M. K.; Sagar, M. V. P.; Reddy, T. L.; Pushpavalli, S. N. C. V. L.; Pal-Bhadra, M. Eur. J. Med. Chem. 2011, 46, 5817. doi: 10.1016/j.ejmech.2011.09.039
6. [6]
  Hamid, M. K. A. E.; Mihovilovic, M. D.; El-Nassan, H. B. Eur. J. Med. Chem. 2012, 57, 323. doi: 10.1016/j.ejmech.2012.09.031
7. [7]
  Kassab, A. E.; Gedawy, E. M. Eur. J. Med. Chem. 2013, 63, 224. doi: 10.1016/j.ejmech.2013.02.011
8. [8]
  Duschinsky, R.; Pleven, E.; Heidelberger, C. J. Am. Chem. Soc. 1957, 79, 4559.
9. [9]
  Pecchi, S.; Renhowe, P. A.; Taylor, C.; Kaufman, S.; Merritt, H.; Wiesmann, M.; Shoemaker, K. R.; Knapp, M.; Ornelas, E.; Hendrickson, T. F.; Fantl, W.; Voliva, C. F. Bioorg. Med. Chem. Lett. 2010, 20, 6895. doi: 10.1016/j.bmcl.2010.10.021
10. [10]
  Keche, A. P.; Hatnapure, G. D.; Tale, R. H.; Rodge, A. H.; Bi-rajdar, S. S.; Kamble, V. M. Bioorg. Med. Chem. Lett. 2012, 22, 3445. doi: 10.1016/j.bmcl.2012.03.092
11. [11]
  Ni, L.; Meng, C. Q.; Sikorski, J. A. Expert. Opin. Ther. Pat. 2004, 14, 1669. doi: 10.1517/13543776.14.12.1669
12. [12]
  Dimmock, J. R.; Elias, D. W.; Beazely, M. A. Kandepu, N. M. Curr. Med. Chem. 1999, 6, 1125.
13. [13]
  Domínguez, J. N.; León, C.; Rodrigues, J.; Gamboa, D. N.; Gut, J.; Rosenthal, P. J. J. Med. Chem. 2005, 48, 3654. doi: 10.1021/jm058208o
14. [14]
  Gacche, R.; Dhole, N. A.; Kamble, S. G.; Bandgar, B. P. J. En-zyme Inhib. Med. Chem. 2008, 23, 28. doi: 10.1080/14756360701306370
15. [15]
  Sharma, V.; Kumar, P.; Pathak, D. J. Heterocycl. Chem. 2010, 47, 491.
16. [16]
  Shao, K. P.; Zhang, X. Yao.; Chen, P. J.; Xue, D. Q.; He, P.; Ma, L. Y.; Zheng, J. X.; Zhang, Q. R.; Liu, H. M. Bioorg. Med. Chem. Lett. 2014, 24, 3877. doi: 10.1016/j.bmcl.2014.06.050
17. [17]
  Chen, P. J.; Yang, A.; Gu, Y. F.; Zhang, X. S.; Shao, K. P.; Xue, D. Q.; He, P.; Jiang, T. F.; Zhang, Q. R.; Liu, H. M. Bioorg. Med. Chem. Lett. 2014, 24, 2741. doi: 10.1016/j.bmcl.2014.04.037
18. [18]
  Tominaga, H.; Ishiyama, M.; Ohseto, F.; Sasamoto, K.; Hamamoto, T.; Suzuki, K.; Watanabe, M. Anal. Commun. 1999, 36, 47. doi: 10.1039/a809656b
1. [1]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
2. [2]
  Jiahao Zeng , Hui Chao . 诱导程序性细胞死亡的金属抗肿瘤药物研究. University Chemistry, 2025, 40(6): 145-159. doi: 10.12461/PKU.DXHX202406019
3. [3]
  Fa Wang , Yu Chen , Hui Chao . Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy. University Chemistry, 2025, 40(7): 200-212. doi: 10.12461/PKU.DXHX202410024
4. [4]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . 高效靶向示踪钙钛矿纳米系统光电增效抗肿瘤. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-. doi: 10.1016/j.actphy.2024.100042
5. [5]
  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
6. [6]
  Aiyi Xin , Jiawei Li , Xinyang Ran , Chuanjiang Fu , Zhiguo Wang . Collaborative Science and Education Based Experimental Design in Organic Chemistry: A Case Study of the Nucleophilic Substitution Reaction of 2-Hydroxymethyl-4,6-Di-Tert-Butylphenol. University Chemistry, 2025, 40(5): 366-375. doi: 10.12461/PKU.DXHX202407031
7. [7]
  Yongqing Kuang , Jie Liu , Jianjun Feng , Wen Yang , Shuanglian Cai , Ling Shi . Experimental Design for the Two-Step Synthesis of Paracetamol from 4-Hydroxyacetophenone. University Chemistry, 2024, 39(8): 331-337. doi: 10.12461/PKU.DXHX202403012
8. [8]
  Yahui HAN , Jinjin ZHAO , Ning REN , Jianjun ZHANG . Synthesis, crystal structure, thermal decomposition mechanism, and fluorescence properties of benzoic acid and 4-hydroxy-2, 2′: 6′, 2″-terpyridine lanthanide complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 969-982. doi: 10.11862/CJIC.20240395
9. [9]
  Aidang Lu , Yunting Liu , Yanjun Jiang . Comprehensive Organic Chemistry Experiment: Synthesis and Characterization of Triazolopyrimidine Compounds. University Chemistry, 2024, 39(8): 241-246. doi: 10.3866/PKU.DXHX202401029
10. [10]
  Xiaofeng Xia , Jielian Zhu . Innovative Comprehensive Experimental Design: Synthesis of 6-Fluoro-N-benzoyl Tetrahydroquinoline. University Chemistry, 2024, 39(10): 344-352. doi: 10.12461/PKU.DXHX202405063
11. [11]
  Aiai WANG , Lu ZHAO , Yunfeng BAI , Feng FENG . Research progress of bimetallic organic framework in tumor diagnosis and treatment. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1825-1839. doi: 10.11862/CJIC.20240225
12. [12]
  Tingting XU , Wenjing ZHANG , Yongbo SONG . Research advances of atomic precision coinage metal nanoclusters in tumor therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2275-2285. doi: 10.11862/CJIC.20240229
13. [13]
  Shuwen SUN , Gaofeng WANG . Design and synthesis of a Zn(Ⅱ)-based coordination polymer as a fluorescent probe for trace monitoring 2, 4, 6-trinitrophenol. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 753-760. doi: 10.11862/CJIC.20240399
14. [14]
  Shiyi WANG , Chaolong CHEN , Xiangjian KONG , Lansun ZHENG , Lasheng LONG . Polynuclear lanthanide compound [Ce₄^ⅢCe₆^Ⅳ(μ₃-O)₄(μ₄-O)₄(acac)₁₄(CH₃O)₆]·2CH₃OH for the hydroboration of amides to amine. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 88-96. doi: 10.11862/CJIC.20240342
15. [15]
  Lihui Jiang , Wanrong Dong , Hua Yang , Yongqing Xia , Hongjian Peng , Jun Yuan , Xiaoqian Hu , Zihan Zeng , Yingping Zou , Yiming Luo . Study on Extraction of p-Hydroxyacetophenone. University Chemistry, 2024, 39(11): 259-268. doi: 10.12461/PKU.DXHX202402056
16. [16]
  Jiahui CHEN , Tingting ZHENG , Xiuyun ZHANG , Wei LÜ . Research progress of near-infrared absorption inorganic nanomaterials in photothermal and photodynamic therapy of tumors. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2396-2414. doi: 10.11862/CJIC.20240106
17. [17]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
18. [18]
  Dong-Xue Jiao , Hui-Li Zhang , Chao He , Si-Yu Chen , Ke Wang , Xiao-Han Zhang , Li Wei , Qi Wei . Layered (C5H6ON)2[Sb2O(C2O4)3] with a large birefringence derived from the uniform arrangement of π-conjugated units. Chinese Journal of Structural Chemistry, 2024, 43(6): 100304-100304. doi: 10.1016/j.cjsc.2024.100304
19. [19]
  Zhaoyang WANG , Chun YANG , Yaoyao Song , Na HAN , Xiaomeng LIU , Qinglun WANG . Lanthanide(Ⅲ) complexes derived from 4′-(2-pyridyl)-2, 2′∶6′, 2″-terpyridine: Crystal structures, fluorescent and magnetic properties. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1442-1451. doi: 10.11862/CJIC.20240114
20. [20]
  Ke-Ai Zhou , Lian Huang , Xing-Ping Fu , Li-Ling Zhang , Yu-Ling Wang , Qing-Yan Liu . Fluorinated metal-organic framework for methane purification from a ternary CH4/C2H6/C3H8 mixture. Chinese Journal of Structural Chemistry, 2023, 42(11): 100172-100172. doi: 10.1016/j.cjsc.2023.100172

Get Citation

PDF

XML

Metrics

PDF Downloads(8)
Abstract views(1997)
HTML views(200)

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