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Design, Synthesis, and Antitumor Activity Evaluation of Trifluoromethyl-Substituted Pyrimidine Derivatives Containing Urea Moiety

Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

In order to find efficient new antitumor drugs, a series of novel pyrimidine derivatives containing urea moiety were designed and synthesized, and the antitumor activity of four human tumor cells was evaluated by MTT analysis. The results showed that most of the target compounds exhibited moderate antitumor activity. In particular, the IC50 (concentration required to achieve 50% inhibition of the tumor cell proliferation) value of compound 2-((4-(4-ethylphenoxy)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-N-((4-ethylphenyl)carba-moyl)acetamide for MGC-803 (human gastric carcinoma cell line) was 2.51 ± 0.17 µmol L–1, the anti-proliferative activity was significantly better than the positive control drug 5-fluorouracil. Molecular docking revealed that this compound can bind well to the active site of epidermal growth factor receptor (EGFR), and it may become a potential antitumor drug.

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REFERENCES

  1. Perupogu, N., Kumar, D.R., and Ramachandran, D., Chem. Data Collect., 2020, vol. 27. https://doi.org/10.1016/j.cdc.2020.100363

  2. Ye, T., Han, Y., Wang, R., Yan, P., Chen, S., Hou, Y., and Zhao, Y., Bioorg. Chem., 2020, vol. 99, p. 103796. https://doi.org/10.1016/j.bioorg.2020.103796

    Article  CAS  PubMed  Google Scholar 

  3. Romu, A.A., Lei, Z., Zhou, B., Chen, Z.S., and Korlipara, V., Bioorg. Med. Chem. Lett., 2017, vol. 27, pp. 4832–4837. https://doi.org/10.1016/j.bmcl.2017.09.048

    Article  CAS  PubMed  Google Scholar 

  4. Zhou, W., Ercan, D., Chen, L., Yun, C.H., Li, D., Capelletti, M., Cortot, A.B., Chirieac, L., Iacob, R.E., Padera, R., Engen, J.R., Wong, K.K., Eck, M.J., Gray, N.S., and Janne, P.A., Nature, 2009, vol. 462, pp. 1070–1074. https://doi.org/10.1038/nature08622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Walter, A.O., Sjin, R.T., Haringsma, H.J., Ohashi, K., Sun, J., Lee, K., Dubrovskiy, A., Labenski, M., Zhu, Z., Wang, Z., Sheets, M., St Martin, T., Karp, R., van Kalken, D., Chaturvedi, P., Niu, D., Nacht, M., Petter, R.C., Westlin, W., Lin, K., Jaw-Tsai, S., Raponi, M., Van Dyke, T., Etter, J., Weaver, Z., Pao, W., Singh, J., Simmons, A.D., Harding, T.C., and Allen, A., Cancer Discov., 2013, vol. 3, pp. 1404–1415. https://doi.org/10.1158/2159-8290.CD-13-0314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cross, D.A., Ashton, S.E., Ghiorghiu, S., Eberlein, C., Nebhan, C.A., Spitzler, P.J., Orme, J.P., Finlay, M.R., Ward, R.A., Mellor, M.J., Hughes, G., Rahi, A., Jacobs, V.N., Red Brewer, M., Ichihara, E., Sun, J., Jin, H., Ballard, P., Al-Kadhimi, K., Rowlinson, R., Klinowska, T., Richmond, G.H., Cantarini, M., Kim, D.W., Ranson, M.R., and Pao, W., Cancer Discov., 2014, vol. 4, pp. 1046–1061. https://doi.org/10.1158/2159-8290.CD-14-0337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Finlay, M.R., Anderton, M., Ashton, S., Ballard, P., Bethel, P.A., Box, M.R., Bradbury, R.H., Brown, S.J., Butterworth, S., Campbell, A., Chorley, C., Colclough, N., Cross, D.A., Currie, G.S., Grist, M., Hassall, L., Hill, G.B., James, D., James, M., Kemmitt, P., Klinowska, T., Lamont, G., Lamont, S.G., Martin, N., McFarland, H.L., Mellor, M.J., Orme, J.P., Perkins, D., Perkins, P., Richmond, G., Smith, P., Ward, R.A., Waring, M.J., Whittaker, D., Wells, S., and Wrigley, G.L., J. Med. Chem., 2014, vol. 57, pp. 8249–8267. https://doi.org/10.1021/jm500973a

    Article  CAS  PubMed  Google Scholar 

  8. Rekunge, D.S., Khatri, C.K., and Chaturbhuj, G.U., Tetrahedron Lett., 2017, vol. 58, pp. 4304–4307. https://doi.org/10.1016/j.tetlet.2017.10.001

    Article  CAS  Google Scholar 

  9. Tokala, R., Bale, S., Janrao, I.P., Vennela, A., Kumar, N.P., Senwar, K.R., Godugu, C., and Shankaraiah, N., Bioorg. Med. Chem. Lett., 2018, vol. 28, pp. 1919–1924. https://doi.org/10.1016/j.bmcl.2018.03.074

    Article  CAS  PubMed  Google Scholar 

  10. Saurat, T., Buron, F., Rodrigues, N., de Tauzia, M.L., Colliandre, L., Bourg, S., Bonnet, P., Guillaumet, G., Akssira, M., Corlu, A., Guillouzo, C., Berthier, P., Rio, P., Jourdan, M.L., Benedetti, H., and Routier, S., J. Med. Chem., 2014, vol. 57, pp. 613–631. https://doi.org/10.1021/jm401138v

    Article  CAS  PubMed  Google Scholar 

  11. Li, J., Huang, L., Yan, J., Zhou, F., Liu, C., and Yan, Y., J. Med. Coll. PLA, 2011, vol. 26, pp. 324–334. https://doi.org/10.1016/s1000-1948(12)60028-8

    Article  CAS  Google Scholar 

  12. Kane, R.C., Farrell, A.T., Saber, H., Tang, S., Williams, G., Jee, J.M., Liang, C., Booth, B., Chidambaram, N., Morse, D., Sridhara, R., Garvey, P., Justice, R., and Pazdur, R., Clin. Cancer Res., 2006, vol. 12, pp. 7271–7278. https://doi.org/10.1158/1078-0432.CCR-06-1249

    Article  CAS  PubMed  Google Scholar 

  13. Eicher, C., Dewerth, A., Kirchner, B., Warmann, S.W., Fuchs, J., and Armeanu-Ebinger, S., Liver Int., 2012, vol. 32, pp. 574–581. https://doi.org/10.1111/j.1478-3231.2011.02729.x

    Article  CAS  PubMed  Google Scholar 

  14. Eicher, C., Dewerth, A., Thomale, J., Ellerkamp, V., Hildenbrand, S., Warmann, S.W., Fuchs, J., and Armeanu-Ebinger, S., Br. J. Cancer, 2013, vol. 108, pp. 334–341. https://doi.org/10.1038/bjc.2012.539

    Article  CAS  PubMed  Google Scholar 

  15. Haddad, Y., Remes, M., Adam, V., and Heger, Z., Drug Discov. Today, 2021, vol. 26, pp. 289–295. https://doi.org/10.1016/j.drudis.2020.10.007

  16. Cherukupalli, S., Chandrasekaran, B., Aleti, R.R., Sayyad, N., Hampannavar, G.A., Merugu, S.R., Rachamalla, H.R., Banerjee, R., and Karpoormath, R., J. Mol. Struct., 2019, vol. 1176, pp. 538–551. https://doi.org/10.1016/j.molstruc.2018.08.104

    Article  CAS  Google Scholar 

  17. Abdel-Mohsen, H.T., Conrad, J., Harms, K., Nohr, D., and Beifuss, U., RSC Adv., 2017, vol. 7, pp. 17427–17441. https://doi.org/10.1039/c6ra28102h

    Article  CAS  Google Scholar 

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Funding

Project supported by the National Natural Science Foundation of China (no. 81773562) and this work was supported by National Key Research Program of Proteins (no. 2018YFE0195100) and Openning fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (no. K2020000X).

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Correspondence to Shan Lihong, Liu Hongmin or Zhang Qiurong.

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The work has no studies involving humans or animals as subjects of the study.

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Liu Limin, Zhengjie, W., Xiujuan, L. et al. Design, Synthesis, and Antitumor Activity Evaluation of Trifluoromethyl-Substituted Pyrimidine Derivatives Containing Urea Moiety. Russ J Bioorg Chem 47, 1301–1311 (2021). https://doi.org/10.1134/S1068162021060157

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