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Статья
2021

3,4-Dihydroquinazolin-8-yl-3-phenylurea Derivatives: Synthesis, VEGFR-2 Kinase Inhibiting Activity, and Molecular Docking


Kunming JiangKunming Jiang, Nali SongNali Song, Chen YangChen Yang, Shiyun TangShiyun Tang, Zhibang WuZhibang Wu, Zhihua LiuZhihua Liu, Zhenjie LiZhenjie Li
Российский журнал общей химии
https://doi.org/10.1134/S107036322109022X
Abstract / Full Text

New 15 compounds have been synthesized targeting the highly conserved active site of VEGFR-2. Some of those have exhibited high anti-proliferation potency against tumor cells and inhibitory activity against VEGFR-2. One of the products (6h) has displayed the most efficient cytotoxic activity against Hela cell line in vitro (IC50 = 6.10 μM) and VEGFR-2 kinase activity (IC50 = 483.1 nM). Molecular docking analysis has indicated 6h as a Type-II inhibitor of VEGFR-2 kinase. In general, the accumulated data prove 3,4-dihydroquinazolin-8-yl-3-phenylurea derivatives to be promising inhibitors of VEGFR-2 for the potential treatment of anti-angiogenesis.

Author information
  • Yunnan Key Laboratory of Tobacco Chemistry, China Tobacco Yunnan Industrial Co., Ltd., 650231, Kunming, ChinaKunming Jiang, Chen Yang, Shiyun Tang, Zhihua Liu & Zhenjie Li
  • Central Laboratory, Yunnan Institute of Traditional Chinese Medicine and Materia Medica, Kunming, 650223, Yunnan, ChinaNali Song
  • Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, 650091, Kunming, ChinaZhibang Wu
References
  1. Bando, H., Weich, H.A., Brokelmann, M., Horiguchi, S., Funata, N., Ogawa, T., and Toi, M., Br. J. Cancer, 2005, vol. 92, p. 553. https://doi.org/10.1038/sj.bjc.6602374
  2. Apte, R.S., Chen, D.S., and Ferrara, N., Cell, 2019, vol. 176, p. 1248. https://doi.org/10.1016/j.cell.2019.01.021
  3. Cheng, K., Liu, C.F., and Rao, G.W., Curr. Med. Chem., 2021, vol. 28, p. 2540. https://doi.org/10.2174/0929867327666200514082425
  4. Li, W., Feng, C., Di, W., Hong, S., Chen, H., Ejaz, M., Yang, Y., and Xu, T.-r., Eur. J. Med. Chem., 2020, vol. 200, p. 112482. https://doi.org/10.1016/j.ejmech.2020.112482
  5. Tannir, N.M., Schwab, G., and Gruenwald, V., Curr. Oncol. Rep., 2017, vol. 19, p. 14. https://doi.org/10.1007/s11912-017-0566-9
  6. Chen, F.M., Fang, Y.F., Zhao, R.R., Le, J.Q., Zhang, B.C., Huang, R., Chen, Z.X., and Shao, J.W., Eur. J. Med. Chem., 2019, vol. 179, p. 916. https://doi.org/10.1016/j.ejmech.2019.06.070
  7. Znati, S., Carter, R., Vasquez, M., Westhorpe, A., Shahbakhti, H., Prince, J., Vlckova, P., De Vellis, C., Bascal, Z., Loizidou, M., and Sharma, R.A., Cancers, 2020, vol. 12, p. 1878. https://doi.org/10.3390/cancers12071878
  8. Stark, D.P., Cook, A., Brown, J.M., Brundage, M.D., Embleton, A.C., Kaplan, R.S., Raja, F.A., Swart, A.M.W., Velikova, G., Qian, W., and Ledermann, J.A., Cancer, 2017, vol. 123, p. 2752. https://doi.org/10.1002/cncr.30657
  9. Cats, A., Lancet Oncol., 2019, vol. 20, p. 323. https://doi.org/10.1016/s1470-2045(18)30892-1
  10. Wang, Y.M., Li, L.J., Fan, J., Dai, Y., Jiang, A., Geng, M.Y., Ai, J., and Duan, W.H., J. Med. Chem., 2018, vol. 61, p. 9085. https://doi.org/10.1021/acs.jmedchem.7b01843
  11. Zang, J., Liang, X.W., Huang, Y.X., Jia, Y.P., Li, X.Y., Xu, W.F., Chou, C.J., and Zhang, Y.J., J. Med. Chem., 2018, vol. 61, p. 5304. https://doi.org/10.1021/acs.jmedchem.8b00384
  12. Shao, W.B., Zheng, Y.T., Liu, J.M., Fu, Y.H., Qi, P.Y., Zhou, X., Wu, Z.B., Wang, P.Y., and Yang, S., Bioorg. Med. Chem. Lett., 2020, vol. 30, p. 5. https://doi.org/10.1016/j.bmcl.2019.126912
  13. Yang, S.M., Yoshioka, M., Strovel, J.W., Urban, D.J., Hu, X., Hall, M.D., Jadhav, A., and Maloney, D.J., Bioorg. Med. Chem. Lett., 2019, vol. 29, p. 1220. https://doi.org/10.1016/j.bmcl.2019.03.014
  14. Panneerselvam, T., Sivakumar, A., Arumugam, S., and Joshi, S.D., Drug Discov. Ther., 2016, vol. 10, p. 188. https://doi.org/10.5582/ddt.2016.01048
  15. Modh, R.P., De Clercq, E., Pannecouque, C., and Chikhalia, K.H., J. Enzym. Inhib. Med. Chem., 2013, vol. 29, p. 100. https://doi.org/10.3109/14756366.2012.755622
  16. Fan, H., Wei, D., Zheng, K., Qin, X., Yang, L., Yang, Y., Duan, Y., Xu, Y., and Hu, L., Eur. J. Med. Chem., 2019, vol. 175, p. 349. https://doi.org/10.1016/j.ejmech.2019.04.015
  17. Li, Y., Xiao, J., Zhang, Q.Z., Yu, W.M., Liu, M.Q., Guo, Y., He, J., and Liu, Y.M., Bioorgan. Med. Chem., 2019, vol. 27, p. 568. https://doi.org/10.1016/j.bmc.2018.12.032
  18. Yu, X., Zhang, X., Zhang, Z., Lin, Y., Wen, Y., Chen, Y., Wang, W., and Zhang, L., Cancer Commun., 2018, vol. 38, p. 51. https://doi.org/10.1186/s40880-018-0321-0
  19. Fassunke, J., Müller, F., Keul, M., Michels, S., Dammert, M.A., Schmitt, A., Plenker, D., Lategahn, J., Heydt, C., Brägelmann, J., Tumbrink, H.L., Alber, Y., Klein, S., Heimsoeth, A., Dahmen, I., Fischer, R.N., Scheffler, M., Ihle, M.A., Priesner, V., Scheel, A.H., Wagener, S., Kron, A., Frank, K., Garbert, K., Persigehl, T., Püsken, M., Haneder, S., Schaaf, B., Rodermann, E., Engel-Riedel, W., Felip, E., Smit, E.F., Merkelbach-Bruse, S., Reinhardt, H.C., Kast, S.M., Wolf, J., Rauh, D., Büttner, R., and Sos, M.L., Nat. Commun., 2018, vol. 9, p. 4655. https://doi.org/10.1038/s41467-018-07078-0
  20. Liang, X., Zhang, J.Q., Liu, Z.C., Zhang, J.H., Yan, J.F., Jin, Y., and Lin, J., Org. Biomol. Chem., 2013, vol. 11, p. 4367. https://doi.org/10.1039/C3OB40368H
  21. Chacko, S., Boshoff, H.I.M., Singh, V., Ferraris, D.M., Gollapalli, D.R., Zhang, M., Lawson, A.P., Pepi, M.J., Joachimiak, A., Rizzi, M., Mizrahi, V., Cuny, G.D., and Hedstrom, L., J. Med. Chem., 2018, vol. 61, p. 4739. https://doi.org/10.1021/acs.jmedchem.7b01839
  22. Jin, Y., Li, H.Y., Lin, L.P., Tan, J., Ding, J., Luo, X., and Long, Y.Q., Bioorg. Med. Chem., 2005, vol. 13, p. 5613. https://doi.org/10.1016/j.bmc.2005.05.045
  23. Shi, L.P., Jiang, K.M., Jiang, J.J., Jin, Y., Tao, Y.H., Li, K., Wang, X.H., and Lin, J., Bioorg. Med. Chem. Lett., 2013, vol. 23, p. 5958. https://doi.org/10.1016/j.bmcl.2013.08.068
  24. Chacko, S., Boshoff, H.I.M., Singh, V., Ferraris, D.M., Gollapalli, D.R., Zhang, M., Lawson, A.P., Pepi, M.J., Joachimiak, A., Rizzi, M., Mizrahi, V., Cuny, G.D., and Hedstrom, L., J. Med. Chem., 2018, vol. 61, p. 4739. https://doi.org/10.1021/acs.jmedchem.7b01839