SIOC 中文
CJOG
Adv search

Chinese Journal of Organic Chemistry >

2022 , Vol. 42 >Issue 11: 3853 - 3862

DOI: https://doi.org/10.6023/cjoc202205028

Synthesis and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Thiazole Structure

  • Honglin Dai ,
  • Xiaojie Si ,
  • Lingling Chi ,
  • Hao Wang ,
  • Chao Gao ,
  • Zhengjie Wang ,
  • Limin Liu ,
  • Jiajie Ma ,
  • Fuqiang Yu ,
  • Hongmin Liu ,
  • Yu Ke ,
  • Qiurong Zhang
Expand
  • aSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
    bCollaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
    cKey Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001
    dState Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou 450052
*E-mail: ;
;
;

Received date: 2022-05-18

  Revised date: 2022-06-28

  Online published: 2022-07-05

Supported by

National Natural Science Foundation of China(U1904163)

Fold

Abstract

A series of 2,4,6-trisubstituted quinazoline derivatives containing thiazole group were designed and synthesized, and their antiproliferative activities against human tumor cell lines (PC-3, H1975, MGC-803 and A549) were determined. 3-((2-(((2-chlorothiazol-5-yl)methyl)thio)-6-methoxyquinazolin-4-yl)amino)benzonitrile (14i) was identified as the most potent compound in antiproliferation against MGC-803 cells, with the value was (4.54±0.32) μmol/L, which was better than the positive control 5-fluorouracil (5-FU) [(8.14±0.68) μmol/L]. Further mechanistic studies showed that compound 14i could inhibit the clonal proliferation and migration of MGC-803 cells. In addition, compound 14i could induce apoptosis of MGC-803 cells and arrest the cell cycle at late period of DNA synthesis/mitotic phase (G2/M) phase. These results indicated that compound 14i could as a potential antitumor drug.

Key words： thiazole; quinazoline; antitumor activity; synthesis

Cite this article

Honglin Dai , Xiaojie Si , Lingling Chi , Hao Wang , Chao Gao , Zhengjie Wang , Limin Liu , Jiajie Ma , Fuqiang Yu , Hongmin Liu , Yu Ke , Qiurong Zhang . Synthesis and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Thiazole Structure[J]. Chinese Journal of Organic Chemistry, 2022 , 42(11) : 3853 -3862 . DOI: 10.6023/cjoc202205028

References

[1]
Siegel, R. L.; Miller, K. D.; Goding Sauer, A.; Fedewa, S. A.; Butterly, L. F.; Anderson, J. C.; Cercek, A.; Smith, R. A.; Jemal, A. CA Cancer J. Clin. 2020, 70, 145.
[2]
Cheng, M.; Yu, X.; Lu, K.; Xie, L.; Wang, L.; Meng, F.; Han, X.; Chen, X.; Liu, J.; Xiong, Y.; Jin, J. J. Med. Chem. 2020, 63, 1216.
[3]
Das, D.; Hong, J. Eur. J. Med. Chem. 2019, 170, 55.
[4]
Gatadi, S.; Gour, J.; Shukla, M.; Kaul, G.; Das, S.; Dasgupta, A.; Malasala, S.; Borra, R. S.; Madhavi, Y. V.; Chopra, S.; Nanduri, S. Eur. J. Med. Chem. 2018, 157, 1056.
[5]
Rakesh, K. P.; Manukumar, H. M.; Gowda, D. C. Bioorg. Med. Chem. Lett. 2015, 25, 1072.
[6]
Ugale, V. G.; Bari, S. B. Eur. J. Med. Chem. 2014, 80, 447.
[7]
Verhaeghe, P.; Azas, N.; Gasquet, M.; Hutter, S.; Ducros, C.; Laget, M.; Rault, S.; Rathelot, P.; Vanelle, P. Bioorg. Med. Chem. Lett. 2008, 18, 396.
[8]
Wan, Z.; Hu, D.; Li, P.; Xie, D.; Gan, X. Molecules 2015, 20, 11861.
[9]
Bansal, R.; Malhotra, A. Eur. J. Med. Chem. 2021, 211, 113016.
[10]
Wilder, C. D. E.; Pavlaki, N.; Dursun, T.; Gyimah, P.; Caldwell-Dunn, E.; Ranieri, A.; Lewis, H. R.; Curtis, M. J. Br. J. Pharmacol. 2018, 175, 1669.
[11]
Zhang, J.; Zhang, S.; Wang, Y.; Xu, W.; Zhang, J.; Jiang, H.; Huang, F. PLoS One 2014, 9, e89473.
[12]
Landre, T.; Des Guetz, G.; Chouahnia, K.; Duchemann, B.; Assie, J. B.; Chouaid, C. J. Cancer Res. Clin. Oncol. 2020, 146, 3333.
[13]
Park, H.; Jung, H. Y.; Mah, S.; Hong, S. Angew. Chem., Int. Ed. Engl. 2017, 56, 7634.
[14]
Ali, S. H.; Sayed, A. R. Synth. Commun. 2020, 51, 670.
[15]
Borcea, A. M.; Ionut, I.; Crisan, O.; Oniga, O. Molecules 2021, 26.
[16]
Sever, B.; Turkes, C.; Altintop, M. D.; Demir, Y.; Akalin Ciftci, G.; Beydemir, S. Arch. Pharm. (Weinheim) 2021, 354, e2100294.
[17]
Wan, Y.; Long, J.; Gao, H.; Tang, Z. Eur. J. Med. Chem. 2021, 210, 112953.
[18]
Abdelhameed, A.; Liao, X.; McElroy, C. A.; Joice, A. C.; Rakotondraibe, L.; Li, J.; Slebodnick, C.; Guo, P.; Wilson, W. D.; Werbovetz, K. A. Bioorg. Med. Chem. Lett. 2020, 30, 126725.
[19]
Kirstein, A. S.; Augustin, A.; Penke, M.; Cea, M.; Korner, A.; Kiess, W.; Garten, A. Cancers (Basel) 2019, 11.
[20]
Nguyen, T. B.; Sakata-Yanagimoto, M.; Fujisawa, M.; Nuhat, S. T.; Miyoshi, H.; Nannya, Y.; Hashimoto, K.; Fukumoto, K.; Bernard, O. A.; Kiyoki, Y.; Ishitsuka, K.; Momose, H.; Sukegawa, S.; Shinagawa, A.; Suyama, T.; Sato, Y.; Nishikii, H.; Obara, N.; Kusakabe, M.; Yanagimoto, S.; Ogawa, S.; Ohshima, K.; Chiba, S. Cancer Res. 2020, 80, 1875.
[21]
Arora, P.; Narang, R.; Nayak, S. K.; Singh, S. K.; Judge, V. Med. Chem. Res. 2016, 25, 1717.
[22]
Flores, E.; Mu?oz-Osses, M.; Torrent, C.; Vásquez-Martínez, Y.; Gómez, A.; Cortez-San Martin, M.; Vega, A.; Martí, A. A.; Godoy, F.; Mascayano, C. Organometallics 2020, 39, 2672.
[23]
Petrou, A.; Fesatidou, M.; Geronikaki, A. Molecules 2021, 26.
[24]
Rouf, A.; Tanyeli, C. Eur. J. Med. Chem. 2015, 97, 911.
[25]
Schadich, E.; Kryshchyshyn-Dylevych, A.; Holota, S.; Polishchuk, P.; Dzubak, P.; Gurska, S.; Hajduch, M.; Lesyk, R. Bioorg. Med. Chem. Lett. 2020, 30, 127616.
[26]
Reddy, B.; Naidu, A.; Dubey, P. K. Asian J. Chem. 2013, 25, 2644.
[27]
Song, P.; Cui, F.; Li, N.; Xin, J.; Ma, Q.; Meng, X.; Wang, C.; Cao, Q.; Gu, Y.; Ke, Y.; Zhang, Q.; Liu, H. Chin. J. Chem. 2017, 35, 1633.
[28]
Wei, X. W.; Yuan, J. M.; Huang, W. Y.; Chen, N. Y.; Li, X. J.; Pan, C. X.; Mo, D. L.; Su, G. F. Eur. J. Med. Chem. 2020, 186, 111851.
Options
Outlines

/

〈 〉