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

doi:10.6023/cjoc202001034

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (6): 1731-1736.DOI: 10.6023/cjoc202001034 Previous Articles Next Articles

新型腙基取代嘧啶衍生物的合成及抗肿瘤活性评价

张洋^a,b, 张路野^a,b, 刘丽敏^a,b, 王涛^a,b, 孟娅琪^a,b, 栗娜^a,b, 李二冬^a,b, 汪正捷^a,b, 刘秀娟^a,b, 郑甲信^a,c, 单丽红^a,b,c,d, 刘宏民^a,b,c,d,e, 张秋荣^a,b,c,d

a 郑州大学药学院郑州 450001;
b 新药创制与药物安全性评价河南省协同创新中心郑州 450001;
c 教育部药物关键制备技术重点实验室郑州 450001;
d 河南省药品质量与评价重点实验室郑州 450001;
e 省部共建食管癌防治国家重点实验室郑州 450052

收稿日期:2020-01-31 修回日期:2020-03-21 发布日期:2020-04-10
通讯作者: 单丽红, 刘宏民, 张秋荣 E-mail:shlh@zzu.edu.cn;liuhm@zzu.edu.cn;zqr409@yeah.net
基金资助:
国家自然科学基金（No.81773562）、国家蛋白质研究项目（No.2018YFE0195100）、省部共建食管癌防治国家重点实验室资助的开放基金（No.K2020000X）资助项目.

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

Received:2020-01-31 Revised:2020-03-21 Published:2020-04-10
Supported by:
Project 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).

1. 201731S.pdf(1338KB)

Abstract

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.

Key words: hydrazone, pyrimidine derivatives, synthesis, antitumor activity

Cite this article

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.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. CA Cancer J. Clin. 2018, 68, 394.
[2] Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D. M.; Pineros, M.; Znaor, A.; Bray, F. Int. J. Cancer 2019, 144, 1941.
[3] Lavi, O.; Gottesman, M. M.; Levy, D. Drug Resist. Updates 2012, 15, 90.
[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.
[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). (孟娅琪, 李二冬, 张洋, 刘栓, 包崇男, 杨鹏, 张路野, 张丹青, 王继宽, 陈雅欣, 栗娜, 辛景超, 赵培荣, 可钰, 张秋荣, 刘宏民, 有机化学, 2019, 39, 2541.)
[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.
[7] Shakya, N.; Vedi, S.; Liang, C.; Yang, F.; Agrawal, B.; Kumar, R. Bioorg. Med. Chem. Lett. 2014, 24, 1407.
[8] Yang, Z.; Fang, Y.; Pham, T. A.; Lee, J.; Park, H. Bioorg. Med. Chem. Lett. 2013, 23, 1519.
[9] Mantipally, M.; Gangireddy, M. R.; Gundla, R.; Badavath, V. N.; Mandha, S. R.; Maddipati, V. C. Bioorg. Med. Chem. Lett. 2019, 29, 2248.
[10] Pouremad, R.; Bahk, K. D.; Shen, Y. J.; Knop, R. H.; Wyrwicz, A. M. NMR Biomed. 1999, 12, 373.
[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.
[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] Nartop, D.; Özkan, E. H.; Gündem, M.; Çeker, S.; Ağar, G.; Öğütcü, H.; Sarı, N. J. Mol. Struct. 2019, 1195, 877.
[14] Rakesh, K. P.; Kumara, H. K.; Ullas, B. J.; Shivakumara, J.; Channe Gowda, D. Bioorg. Chem. 2019, 90, 103093.
[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.
[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.
[17] Kumar, K. S.; Ganguly, S.; Veerasamy, R.; De Clercq, E. Eur. J. Med. Chem. 2010, 45, 5474.
[18] Saadaoui, I.; Krichen, F.; Ben Salah, B.; Ben Mansour, R.; Miled, N.; Bougatef, A.; Kossentini, M. J. Mol. Struct. 2019, 1180, 344.
[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.
[20] Peng, X.; Liu, P.; Pang, B.; Yao, Y.; Wang, J.; Zhang, K. Carbohydr. Polym. 2019, 216, 113.
[21] Abdel-Mohsen, H. T.; Conrad, J.; Harms, K.; Nohr, D.; Beifuss, U. RSC Adv. 2017, 7, 17427.
[22] Minn, K.; Braun, P.; Sachse, B.; Wicke, H. DE 4029648, 1992.

新型腙基取代嘧啶衍生物的合成及抗肿瘤活性评价

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

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang. Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 650-656.
[2]	Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.
[3]	Luyao Li, Zhongwen He, Zhenguo Zhang, Zhenhua Jia, Teck-Peng Loh. Application of Triaryl Carbenium in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 421-437.
[4]	Qinggang Mei, Qinghan Li. Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 398-408.
[5]	Shihang Yu, Jiawei Liu, Biyu An, Qinghua Bian, Min Wang, Jiangchun Zhong. Asymmetric Synthesis of the Contact Sex Pheromone of Neoclytus acuminatus acuminatus (Fabricius) [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 301-308.
[6]	Weiqing Yang, Yanbing Ge, Yuanyuan Chen, Ping Liu, Haiyan Fu, Menglin Ma. Design and Synthesis of Fluorescent 1,8-Napthalimide Derivatives and Their Identification of Cysteine [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 180-194.
[7]	Qianfan Zhao, Yongzheng Chen, Shiming Zhang. Application and Mechanism Study of Carbon-Based Metal-Free Catalysts in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 137-147.
[8]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[9]	Huakun Wang, Xiaolong Ren, Yining Xuan. Study of the Halide Salt Catalyzed [3＋2] Cycloaddition of α,β-Epoxy Carboxylate with Isocyanate [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 251-258.
[10]	Yukun Jin, Baoyi Ren, Fushun Liang. Visible Light-Mediated Selective C—F Bond Cleavage of Trifluoromethyl Groups and Its Application in Synthesizing gem-Difluoro-Containing Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 85-110.
[11]	Cuiyun Ma, Hailan Luo, Fuhua Zhang, Dan Guo, Shuxing Chen, Fei Wang. Green Biosynthesis, Photophysical Properties and Application of 3-Pyrrolyl BODIPY [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 216-223.
[12]	Bozhen Wang, Jie Zhang, Chunhui Nian, Mingming Jin, Miaomiao Kong, Wulan Li, Wenfei He, Jianzhang Wu. Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 232-241.
[13]	Yang Li, Jinding Yuan, Di Zhao. Deep Eutectic Solvent of 1,3-Dimethylurea/L-(+)-Tartaric Acid for the Green Synthesis of (E)-2-Styrylquinoline-3-carboxylic Acid Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3268-3276.
[14]	Dandan Sui, Nannan Cen, Ruoqu Gong, Yang Chen, Wenbo Chen. Supporting-Electrolyte-Free Electrochemical Synthesis of Trifluoromethylated Oxindoles in Continuous Flow [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3239-3245.
[15]	Ruixia Cao, Yuping Jia. Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3304-3311.