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Chinese Journal of Organic Chemistry >

2022 , Vol. 42 >Issue 9: 2793 - 2805

DOI: https://doi.org/10.6023/cjoc202205016

ARTICLES

Synthesis and in Vitro Anti-tumor Activity of Novel Spliced Compounds of Zidovudine and 4-Anilinoquinazolines

  • Guangping Liang ,
  • Wei Wang ,
  • Xuxiu Zhu ,
  • Guangyan Liang ,
  • Jun Yang ,
  • Daoping Wang
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  • a Department of Pharmacy, Zunyi Medical and Pharmaceutical College, Zunyi, Guizhou 563006
    b Public Laboratory Centre for Clinical Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000
    c Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014
* Corresponding authors. E-mail: ;

Received date: 2022-05-11

  Revised date: 2022-07-04

  Online published: 2022-08-18

Supported by

Guizhou Provincial Natural Science Foundation([2019]1356); Doctoral Research Program of Zunyi Medical and Pharmaceutical College(BS2018001)

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Abstract

Seventeen novel compounds of Zidovudine and 4-anilinoquinazoline were synthesized for use as anti-tumor reagents. The target compounds are subjected to antitumor screening against human cancer cells, namely, A549 (lung carcinoma), A549/DDP (lung carcinoma/Cisplatin-resistant), HepG2 (liver carcinoma), Hela (cervical carcinoma), and MCF-7 (breast carcinoma), using methyl thiazolyl tetrazolium (MTT) assay. In addition, their inhibition of epidermal growth factor receptor (EGFR) was assessed by enzyme linked immunosorbent assay (ELISA). Anticancer bioassays indicated that most of the compounds exhibited appreciable anticancer activity against five human cancer cell lines. In particular, 1-(4-(5-(((4-((2-chloro- 4-iodophenyl)amino)-6-methoxyquinazolin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)- 5-methylpyrimidine-2,4(1H,3H)-dione (8b) was found to be the most potent anticancer agent with an IC50 value of (0.79±0.18) μmol/L against HepG2, respectively. Among the compounds tested, 1-(4-(5-(((4-((3-chloro-4-fluorophenyl)amino)-6- methoxyquinazolin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4 (1H,3H)-dione (8a) and 1-(5-(hydroxymethyl)-4-(4-(((7-methoxy-4-((3,4,5-trifluorophenyl)amino)quinazolin-6-yl)oxy)me- thyl)-1H-1,2,3-triazol-1-yl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (8l) showed significant inhibition against the five human cancer cell lines. Molecular docking results also showed that compounds 8a and 8l bound well to the EGFR binding sites.

Key words： quinazoline; zidovudine; derivatives; antitumor; epidermal growth factor receptor (EGFR) inhibitors

Cite this article

Guangping Liang , Wei Wang , Xuxiu Zhu , Guangyan Liang , Jun Yang , Daoping Wang . Synthesis and in Vitro Anti-tumor Activity of Novel Spliced Compounds of Zidovudine and 4-Anilinoquinazolines[J]. Chinese Journal of Organic Chemistry, 2022 , 42(9) : 2793 -2805 . DOI: 10.6023/cjoc202205016

References

[1]
(a) Siegel, R. L.; Miller, K. D.; Fuchs, H. E.; Jemal, A. Ca-Cancer J. Clin. 2022, 72, 7.
[1]
(b) Fidler, M. M.; Bray, F.; Soerjomataram, I. Scand. J. Public Healt. 2018, 46, 27.
[2]
Sung, H.; Ferlay, J.; Siegel, R. L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Ca-Cancer J. Clin. 2021, 71, 209
[3]
Burstein, H. J.; Krilov, L.; Aragon-Ching, J. B.; Baxter, N. N.; Chiorean, E. G.; Chow, W. A.; Groot, J. F. D.; Devine, S. M.; G DuBois, S.; El-Deiry, W. S.; Epstein, A. S.; Heymach, J.; Jones, J. A.; Mayer, D. K.; Miksad, R. A.; Pennell, N. A.; Sabel, M. S.; Schilsky, R. L.; Schuchter, L. M.; Tung, N.; Winkfield, K. M.; Wirth, L. J.; Dizon, D. S. J. Clin. Oncol. 2017, 35, 1341.
[4]
(a) Chong, C. R.; Jänne, P. A. Nat. Med. 2013, 19, 1389.
[4]
(b) Liu, Q.; Yu, S.; Zhao, W.; Qin, S.; Chu, Q.; Wu, K. Mol. Cancer 2018, 17, 53.
[4]
(c) Leonetti, A.; Sharma, S.; Minari, R.; Perego, P.; Giovannetti, E.; Tiseo, M. Br. J. Cancer 2019, 121, 725.
[4]
(d) Pao, W.; Miller, V. A.; Politi, K. A.; Riely, G. J.; Somwar, R.; Zakowski, M. F.; Kris, M. G.; Varmus, H. PLoS Med. 2005, 2, 225.
[5]
Lu, X.; Yu, L.; Zhang, Z.; Ren, X.; Smaill, J. B.; Ding, K. Med. Res. Rev. 2018, 38, 1550.
[6]
(a) Han, C.; Ren, J.; Su, F.; Hu, X.; Li, M.; Wang, Z.; Wu, L. Anti-Cancer Agents Med. Chem. 2020, 20, 724
[6]
(b) Chen, L.; Zhang, Y.; Wang, C.; Tang, Z.; Meng, Q.; Sun, H.; Qi, Y.; Ma, X.; Li, L.; Li, Y.; Xu, Y. Bioorg. Chem. 2021, 114, 105045.
[7]
Bazarbachi, A.; Nasr, R.; El-Sabban, M.; Mahé, A.; Mahieux, R.; Gessain, A.; Darwiche, N.; Dbaibo, G.; Kersual, J.; Zermati, Y.; Dianoux, L.; Chelbi-Alix, M. K.; Thé, H. D.; Hermine, O. Leukemia 2000, 14, 716.
[8]
(a) Schneider, M. A.; Buzdin, A. A.; Weber, A.; Clavien, P. A.; Borger, P. Viruses 2021, 13, 2396.
[8]
(b) Lewandowski, D.; Lewandowska, M.; Ruszkowski, P.; Pińska, A.; Schroeder, G. PLoS One 2015, 10, e0126251.
[8]
(c) Namba, T.; Kodama, R.; Moritomo, S.; Hoshino, T.; Mizushima, T. Cell Death Dis. 2015, 6, e1795.
[9]
(a) Collier, A. C.; Helliwell, R. J.; Keelan, J. A.; Paxton, J. W.; Mitchell, M. D.; Tingle, M. D. Toxicol. Appl. Pharmacol. 2003, 192, 164.
[9]
(b) Humer, J.; Ferko, B.; Waltenberger, A.; Rapberger, R.; Pehamberger, H.; Muster, T. Melanoma Res. 2008, 18, 314.
[9]
(c) Morgan, R. J.; Newman, E. M.; Sowers, L.; Scanlon, K.; Harrison, J.; Akman, S.; Leong, L.; Margolin, K.; Niland, J.; Raschko, J.; Somlo, G.; Carroll, M.; Chow, W.; Tetef, M.; Hamasaki, V.; Yen, Y.; Doroshow, J. H. Cancer Chemother. Pharmacol. 2003, 51, 459.
[9]
(d) Wu, Y.; Xiao, Q.; Jiang, Y.; Fu, H.; Ju, Y.; Zhao, Y. Nucleosides, Nucleotides Nucleic Acids 2004, 23, 1797.
[9]
(e) Cook, L. B.; Phillips, A. A. Blood 2021, 137, 459.
[9]
(f) Malpica, L.; Castro, D.; Enriquez, D. J.; Oviedo-Pecho, R.; Peña, C.; Idrobo, H.; Fiad, L.; Prates, M.; Valcarcel, B.; Paredes, A.; Sánchez, G.; Moisés, C.; Castillo, J. J.; Villela, L.; Ramos, J. C.; Biglione, M.; Beltran, B. E. Leuk. Lymphoma 2022, 63, 315.
[9]
(g) Bazarbachi, A.; Plumelle, Y.; Ramos, J. C.; Tortevoye, P.; Otrock, Z.; Taylor, G.; Gessain, A.; Harrington, W.; Panelatti, G.; Hermine, O. J. Clin. Oncol. 2010, 28, 4177.
[10]
(a) Butti, R.; Das, S.; Gunasekaran, V. P.; Yadav, A. S.; Kumar, D.; Kundu, G. C. Mol. Cancer 2018, 17, 34.
[10]
(b) Talukdar, S.; Emdad, L.; Das, S. K.; Fisher, P. B. Adv. Cancer Res. 2020, 147, 161.
[11]
(a) Khattab, R. R.; Alshamari, A. K.; Hassan, A. A.; Elganzory, H. H.; El-Sayed, W. A.; Awad, H. M.; Nossier, E. S.; Hassan, N. A. J. Enzyme Inhib. Med. Chem. 2021, 36, 504.
[11]
(b) Nipate, A. S.; Jadhav, C. K.; Chate, A. V.; Deshmukh, T. R.; Sarkate, A. P.; Gill, C. H. ChemistrySelect 2021, 6, 5173.
[11]
(c) Bonandi, E.; Christodoulou, M. S.; Fumagalli, G.; Perdicchia, D.; Rastelli, G.; Passarella, D. Drug Discovery Today 2017, 22, 1572.
[12]
Plyasova, A. A.; Berrino, E.; Khan, I. I.; Veselovsky, A. V.; Pokrovsky, V. S.; Angeli, A.; Ferraroni, M.; Supuran, C. T.; Pokrovskaya, M. V.; Alexandrova, S. S.; Gladilina, Y. A.; Sokolov, N. N.; Hilal, A.; Carta, F.; Zhdanov, D. D. J. Med. Chem. 2021, 64, 11432.
[13]
Wang, Y.; Lv, Z.; Chen, F.; Wang, X.; Gou, S. J. Med. Chem. 2021, 64, 12877.
[14]
Li, R.-D.; Zhang, X.; Li, Q.-Y.; Ge, Z.-M.; Li, R.-T. Bioorg. Med. Chem. Lett. 2011, 21, 3637.
[15]
(a) de Alencar, D.; Gonçalves, J.; Vieira, A.; Cerqueira, S. A.; Sebastião, C.; Leitão, M.; Francescato, G.; Antenori, P.; Soares, H.; Petronilho, A. Molecules 2021, 26, 6720.
[15]
(b) Berrino, E.; Angeli, A.; Zhdanov, D.; Kiryukhina, A.; Milaneschi, A.; De Luca, A.; Bozdag, M.; Carradori, S.; Selleri, S.; Bartolucci, G.; Peat, T.; Ferraroni, M.; Supuran, C.; Carta, F. J. Med. Chem. 2020, 63, 7392.
[16]
Zhao, Y.-J.; Meng, J.; Hu, R.-J.; Qie, Z.-G. Coal Chem. Ind. (Shijiazhuang, China) 2021, 44, 138. (in Chinese)
[16]
(赵永杰, 孟建, 胡瑞娟, 郄正刚, 煤炭与化工, 2021, 44, 138.)
[17]
Jassem, A. M.; Dhumad, A. M. ChemistrySelect 2021, 6, 2641.
[18]
Liang, G. P.; Yang, J.; Zhu, X. X.; Wen, L. D. CN 114437161, 2022.
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