Citation: Sun Jiajing, Zhou Likai, Tan Guanhai, Li Shuai, Wang Shuxia, Chen Hua, Li Xiaoliu. Synthesis and Anti-tumor Activity of Novel Quinazolin-4-one Derivatives[J]. Chinese Journal of Organic Chemistry, ;2017, 37(2): 455-461. doi: 10.6023/cjoc201607045 shu

Synthesis and Anti-tumor Activity of Novel Quinazolin-4-one Derivatives

Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002

Corresponding author: Chen Hua, hua-todd@163.com Li Xiaoliu, lixl@hbu.cn
Received Date: 29 July 2016
Revised Date: 13 September 2016

Fund Project: the National Natural Science Foundation of China 21372060the Hebei Provincal Natural Science Fund for Distinguished Young Scholars (Incubation) B2015201005

Figures(4)

A series of novel C-2 and N-3 disubstituted quinazolin-4(3H)-one derivatives 5 possessing amino acid chain were synthesized by the addition reaction of imine with iminoketene and aromatization using anthranilic acid, aromatic aldehyde and glycine ethyl ester as starting materials. After elimination of carboxymethyl in the acidic condition, novel quinazolin-4(3H)-one derivatives 9 bearing amino side chain were designed and synthesized by SN2 substitution reaction. The compounds were evaluated for their anti-proliferation activities against four tumor cells. The results showed that some of the compounds, such as 9ba and 9bc showed significantly anti Hela activity with the IC₅₀ values of 8.16 μM and 7.47 μM, respectively, while 9bc and 9bd against A549 with the IC₅₀ values of 5.62 μM and 9.54 μM, respectively. Structure activity relationship analysis of these analogues suggested that coumarin substituent (extended π planar aromatic ring) on C-2 position and the introduction of amino side chain should be favorable to their anti-tumor activities.
- quinazolin-4-one,
- anti-tumor activity,
- iminoketene,
- amino side chain,
- elimination of carboxymethyl,
- coumarin
1. [1]
  Khan, I.; Zaib, S.; Batool, S.; Abbas, N.; Ashraf, Z.; Iqbal, J.; Saeed, A. Bioorg. Med. Chem. 2016, 24, 2361. doi: 10.1016/j.bmc.2016.03.031
2. [2]
  Khan, I.; Ibrar, A.; Abbas, N.; Saeed, A. Eur. J. Med. Chem. 2014, 76, 193. doi: 10.1016/j.ejmech.2014.02.005
3. [3]
  Khan, I.; Ibrar, A.; Ahmed, W.; Saeed, A. Eur. J. Med. Chem. 2015, 90, 124. doi: 10.1016/j.ejmech.2014.10.084
4. [4]
  Ou, J. J.; Liu, K. C.; Wang, Y.; Zhang, H.; Liu, R. Q.; Li, Q. B.; Wang, Q. M.; Li, Y. Q.; Rui, C. H.; Liu S. Z. Chin. J. Org. Chem. 2014, 34, 526 (in Chinese). doi: 10.6023/cjoc201310022
5. [5]
  Wang, Z.-Z.; Tang, Y. Tetrahedron 2016, 72, 1330. doi: 10.1016/j.tet.2016.01.027
6. [6]
  Kim, N. Y.; Cheon, C.-H. Tetrahedron Lett. 2014, 55, 2340. doi: 10.1016/j.tetlet.2014.02.065
7. [7]
  Yu, C. W.; Chang, P. T.; Hsin, L. W.; Chern, J. W. J. Med. Chem. 2013, 56, 6775. doi: 10.1021/jm400564j
8. [8]
  Deepak, G.; Kumar, R.; Roy, R. K.; Sharma, A.; Ali, I. Med. Chem. Res. 2013, 22, 3282. doi: 10.1007/s00044-012-0293-6
9. [9]
  Johannes, K.; Martens, J. Tetrahedron 2010, 66, 242. doi: 10.1016/j.tet.2009.10.107
10. [10]
  Unsworth, W. P.; Coulthard, G.; Kitsiou, C.; Taylor, R. J. K. J. Org. Chem., 2014, 79, 1368. doi: 10.1021/jo402768r
11. [11]
  Kametani, T.; Van LoC C.; Higa, T.; Koizumi, M.; Ihara, M.; Fukumoto, K. J. Am. Chem. Soc. 1977, 99, 2306. doi: 10.1021/ja00449a047
12. [12]
  Xu, S.; Xu, S. P.; Li, L. M. Acta Pharm. Sin. 2002, 37, 113 (in Chinese).
13. [13]
  Hou, B. L.; Ai, Y.; Wang, C. L.; Zhang, N.; Yang, L.; Liu, Z. L.; Liu, J. L. Chin. J. Org. Chem. 2016, 36, 121 (in Chinese). doi: 10.6023/cjoc201507012
14. [14]
  Nacro, K.; Charles, Z.; Guzzo, P. R.; Herr, R. J.; Peace, D.; Friedrich, T. D. Bioorg. Med. Chem. 2007, 15, 4237. doi: 10.1016/j.bmc.2007.03.067
15. [15]
  Mayer, J. P.; Lewis, G. S.; Curtis, M. J.; Zhang, J. W. Tetrahedron Lett. 1997, 38, 8445. doi: 10.1016/S0040-4039(97)10276-3
16. [16]
  Chen, H.; Li, S.; Yao, Y. C.; Zhou, L. K.; Zhao, J. P.; Gu, Y. J.; Wang, K. R.; Li, X. L. Bioorg. Med. Chem. Lett. 2013, 23, 4785. doi: 10.1016/j.bmcl.2013.07.009
17. [17]
  Gunaratnam, M.; Swank, S.; Haider, S. M.; Galesa, K.; Reszka, A. P.; Beltran, M.; Cuenca, F.; Fletcher, J. A.; Neidle, S. J. Med. Chem. 2009, 52, 3774. doi: 10.1021/jm900424a
18. [18]
  Chen, G. S.; Kalchar, S.; Kuo, C.-W.; Chang, C.-S.; Usifoh, C. O.; Chern, J.-W. J. Org. Chem. 2003, 68, 2502. doi: 10.1021/jo0263420
19. [19]
  Venkata Sairam, K.; Gurupadayya, B. M.; Chandan, R. S.; Nagesha, D. K.; Vishwanathan, B. Curr. Drug Delivery 2016, 13, 186. doi: 10.2174/1567201812666150702102800
20. [20]
  Mosmann, T. J. Immunol. Methods 1983, 65, 55. doi: 10.1016/0022-1759(83)90303-4
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]
  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
3. [3]
  Xiaoning TANG , Junnan LIU , Xingfu YANG , Jie LEI , Qiuyang LUO , Shu XIA , An XUE . Effect of sodium alginate-sodium carboxymethylcellulose gel layer on the stability of Zn anodes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1452-1460. doi: 10.11862/CJIC.20240191
4. [4]
  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
5. [5]
  Benhua Wang , Chaoyi Yao , Yiming Li , Qing Liu , Minhuan Lan , Guipeng Yu , Yiming Luo , Xiangzhi Song . 一种基于香豆素氟离子荧光探针的合成、表征及性能测试——“科研反哺教学”在有机化学综合实验教学中的探索与实践. University Chemistry, 2025, 40(6): 201-209. doi: 10.12461/PKU.DXHX202408070
6. [6]
  Zhuoming Liang , Ming Chen , Zhiwen Zheng , Kai Chen . Multidimensional Studies on Ketone-Enol Tautomerism of 1,3-Diketones By ¹H NMR. University Chemistry, 2024, 39(7): 361-367. doi: 10.3866/PKU.DXHX202311029
7. [7]
  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
8. [8]
  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
9. [9]
  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
10. [10]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
11. [11]
  Jianjun LI , Mingjie REN , Lili ZHANG , Lingling ZENG , Huiling WANG , Xiangwu MENG . UV-assisted degradation of tetracycline hydrochloride by MnFe₂O₄@activated carbon activated persulfate. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1869-1880. doi: 10.11862/CJIC.20240187
12. [12]
  Yue Zhao , Yanfei Li , Tao Xiong . Copper Hydride-Catalyzed Nucleophilic Additions of Unsaturated Hydrocarbons to Aldehydes and Ketones. University Chemistry, 2024, 39(4): 280-285. doi: 10.3866/PKU.DXHX202309001
13. [13]
  Liangzhen Hu , Li Ni , Ziyi Liu , Xiaohui Zhang , Bo Qin , Yan Xiong . A Green Chemistry Experiment on Electrochemical Synthesis of Benzophenone. University Chemistry, 2024, 39(6): 350-356. doi: 10.3866/PKU.DXHX202312001
14. [14]
  Guojie Xu , Fang Yu , Yunxia Wang , Meng Sun . Introduction to Metal-Catalyzed β-Carbon Elimination Reaction of Cyclopropenones. University Chemistry, 2024, 39(8): 169-173. doi: 10.3866/PKU.DXHX202401060
15. [15]
  Jingzhao Cheng , Shiyu Gao , Bei Cheng , Kai Yang , Wang Wang , Shaowen Cao . 4-氨基-1H-咪唑-5-甲腈修饰供体-受体型氮化碳光催化剂的构建及其高效光催化产氢研究. Acta Physico-Chimica Sinica, 2024, 40(11): 2406026-. doi: 10.3866/PKU.WHXB202406026
16. [16]
  Linjie ZHU , Xufeng LIU . Synthesis, characterization and electrocatalytic hydrogen evolution of two di-iron complexes containing a phosphine ligand with a pendant amine. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 939-947. doi: 10.11862/CJIC.20240416
17. [17]
  Lisha LEI , Wei YONG , Yiting CHENG , Yibo WANG , Wenchao HUANG , Junhuan ZHAO , Zhongjie ZHAI , Yangbin DING . Application of regenerated cellulose and reduced graphene oxide film in synergistic power generation from moisture electricity generation and Mg-air batteries. Chinese Journal of Inorganic Chemistry, 2025, 41(6): 1151-1161. doi: 10.11862/CJIC.20240202
18. [18]
  Yurong Tang , Yunren Shi , Yi Xu , Bo Qin , Yanqin Xu , Yunfei Cai . Innovative Experiment and Course Transformation Practice of Visible-Light-Mediated Photocatalytic Synthesis of Isoquinolinone. University Chemistry, 2024, 39(5): 296-306. doi: 10.3866/PKU.DXHX202311087
19. [19]
  Yihui Song , Shangshang Qin , Kai Wu , Chengyun Jin , Bin Yu . 生物化学在高水平创新型药学人才培养中的交叉融合应用——以去甲基化酶LSD1抑制剂的活性评价为例. University Chemistry, 2025, 40(6): 341-352. doi: 10.12461/PKU.DXHX202406018
20. [20]
  Yonghui ZHOU , Rujun HUANG , Dongchao YAO , Aiwei ZHANG , Yuhang SUN , Zhujun CHEN , Baisong ZHU , Youxuan ZHENG . Synthesis and photoelectric properties of fluorescence materials with electron donor-acceptor structures based on quinoxaline and pyridinopyrazine, carbazole, and diphenylamine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 701-712. doi: 10.11862/CJIC.20230373

Get Citation

PDF

XML

Metrics

PDF Downloads(22)
Abstract views(1895)
HTML views(352)

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