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Design, Synthesis, and Biological Evaluation of Novel Pyrazolo[1,5-a]pyrimidine and 1,3-Benzodiazine Derivatives as Potent Antitumor Agents

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Abstract

Based on the molecular docking simulation and structure of larotrectinib, some larotrectinib derivatives as antitumor compounds were designed and synthesized. The antitumor activities of the synthesized compounds were tested by A549 and H1975 cell lines with larotrectinib as the positive control drugs. The molecular docking of the selected compounds with protein was carried out to further explain the binding modes and the ADME data of the compounds were predicted, which showed that the compounds had good physicochemical property and biological characteristics. The results showed that the selected compounds had further research potential.

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REFERENCES

  1. Al-Azmi, A., Curr. Org. Chem., 2019, vol. 23, p. 721. https://doi.org/10.2174/1385272823666190410145238

    Article  CAS  Google Scholar 

  2. Nadia, H.M., Thoraya, H.K., and Sherif, M.H.S., Synth. Commun., 2022, vol. 52, p. 1139. https://doi.org/10.1080/00397911.2022.2074301

    Article  CAS  Google Scholar 

  3. Cherukupalli, S., Karpoormath, R., Chandrasekaran, B., Hampannavar, G.A., Thapliya, N., and Palakollu, V.N., Eur. J. Med. Chem., 2016, vol. 126, p. 298. https://doi.org/10.1016/j.ejmech.2016.11.019

    Article  CAS  Google Scholar 

  4. Heathcote, D.A., Patel, H., Krol, S.H.B, Hazel, P., Periyasamy, M., Alikian, M., Kanneganti, S.K., Jogalekar, A.S., Scheiper, B., and Barbazanges, M., J. Med. Chem., 2010, vol. 53, p. 8508. https://doi.org/10.1021/jm100732t

    Article  CAS  Google Scholar 

  5. Kosugi, T., Mitchell, D.R., Fujino, A., Imai, M., Kambe, M., Kobayashi, S., Makino, H., Matsueda, Y., Oue, Y., and Komatsu, K., J. Med. Chem., 2012, vol. 55, p. 6700. https://doi.org/10.1021/jm3013954

    Article  CAS  Google Scholar 

  6. Sankaranarayanan, J., and Kalegowda, S., Polycycl. Aromat. Comp., 2021, vol. 41, p. 858. https://doi.org/10.1080/10406638.2019.1625065

    Article  CAS  Google Scholar 

  7. Almehmadi, S.J., Alsaedi, A.M.R., Harras, M.F., Farghaly, T.A., Bioorg. Chem., 2021, vol, 117, p. 105. https://doi.org/10.1016/j.bioorg.2021.105431

  8. Kamal, A., Tamboli, J.R., Nayak, V.L., Adil, S.F., Vishnuvardhan, M.V.P.S., and Ramakrishna, S., Bioorg. Med. Chem. Lett., 2013, vol. 23, p. 3208. https://doi.org/10.1016/j.bmcl.2013.03.129

    Article  CAS  Google Scholar 

  9. Bharath, Y., Basaveswara, R.V.M., and Pal, M., Lett. Drug. Des. Discov., 2017, vol, 14, p. 1206. https://doi.org/10.2174/1570180814666170125125654

  10. Shen, J., Deng, X.X., Sun, R., Tavallaie, M.S., Wang, J.T., Cai, Q.Q., Ce, L., Lei, S.W., Fu, L and Jiang, F.Q., Eur. J. Med. Chem., 2020, vol. 208, p. 112850. https://doi.org/10.1016/j.ejmech.2020.112850

    Article  CAS  Google Scholar 

  11. Al-Adiwish, W.M., Tahir, M.I.M., Siti-Noor-Adnalizawati, A., Hashimet, S.F., Ibrahim, N., and Yaacob, W.A., Eur. J. Med. Chem., 2013, vol. 64, p. 464. https://doi.org/10.1002/chin.201343170

    Article  CAS  Google Scholar 

  12. Li, P., Cai, S., Zhao, T., Xu, L., Guan, D.Z., Li, J.R., Zhou, J.P., and Zhang, H.B., Bioorg. Med. Chem. Lett., 2021, vol. 53, p. 128409. https://doi.org/10.1016/j.bmcl.2021.128409

    Article  CAS  Google Scholar 

  13. Xu, J., Liu, H., Li, G., He, Y., Ding, R., Wang, X., Feng, M., Zhang, S., Chen, Y., and Li, S., Z. Naturforsch. B., 2012, vol. 67, p. 827. https://doi.org/10.5560/znb.2012-0047

    Article  CAS  Google Scholar 

  14. Raffa, D., Maggio, B., Raimondi, M.V., Cascioferroet, S., Plescia, F., Cancemial, G., and Daidone, G., Eur. J. Med. Chem., 2015, vol. 97, p. 732. https://doi.org/10.1002/chin.201532300

    Article  CAS  Google Scholar 

  15. Auti, P.S., George, G., and Paul, A.T., RSC Adv., 2020, vol. 10, p. 41353. https://doi.org/10.1039/D0RA06642G

    Article  CAS  Google Scholar 

  16. Pawar, V.G., Sos, M.L., Rode, H.B., Rabilleret, M., Heynck, S., Otterlo, V., Willem, A.L., Thomas, R.K., and Rauhal, D., J. Med. Chem., 2010 vol. 53, p. 2892. https://doi.org/10.1021/jm901877j

    Article  CAS  Google Scholar 

  17. Jiang, K., Song, N., Yang, C., Tang, S.Y., Wu, Z.B., Liu, Z.H and Li, Z.J., Russ. J. Gen. Chem., 2021, vol. 91, p. 1757. https://doi.org/10.1134/S1070

    Article  Google Scholar 

  18. Cai, Z.-Q., Zhao, C.-K., Li, M.-Y., Shuai, X.-M., Ding, H.-G., Wang, Q.-L., Fu, J., Jin, Z.-S., Li, S., and Zhao, L.-J., J. Chem. Res., 2019, vol. 43, p. 98. https://doi.org/10.1177/1747519819841831

    Article  CAS  Google Scholar 

  19. Bondock, S., Albormani, O., and Fouda, A.M., Russ. J. Gen. Chem., 2022, vol. 92, p. 1098. https://doi.org/10.1134/S1070363222060226

    Article  CAS  Google Scholar 

  20. Lo, Q.A., Sale, D., Braddock, D.C., and Davies, R.P., ACS. Catal., 2018, vol. 8, p. 101. https://doi.org/10.1021/acscatal.7b03664

    Article  CAS  Google Scholar 

  21. Tretyakov, N.A., Bashorina, N.V., Belozerova, A.I., and Maslivets, A.N., Russ. J. Org. Chem., 2021, vol. 57, p. 1425. https://doi.org/10.1134/S1070428021090062

    Article  Google Scholar 

  22. Wang, Y.B., Ling, J., Zhang, Y., Zhang, A., ang Yao, Q.Z., Eur. J. Org. Chem., 2015, vol. 19, p. 4153. https://doi.org/10.1002/ejoc.201500279

    Article  CAS  Google Scholar 

  23. Marinova, P., Marinov, M., Kazakova, M., Feodorova, Ya., Blazheva, D., Slavchev, A., Georgiev, D., Nikolova, I., Sbirkova-Dimitrova, H., Sarafian, V., and Stoyanov, N., Russ. J. Inorg. Chem., 2021, vol. 66, p. 1930. https://doi.org/10.1134/S0036023621130052

    Article  Google Scholar 

  24. Liu, J., Gong, Y.L., Shi, J.T., Hao, X.C., and Wang, Y., Eur. J. Med. Chem., 2020, vol. 194, p. 112244. https://doi.org/10.1016/j.ejmech.2020.112244

    Article  CAS  Google Scholar 

  25. Kovalev, V.V., Kokunov, Y.V., Shmelev, M.A., Voronina, Yu.K., Kiskin, M.A., Popov, L.D., and Eremenko, I.L., Russ. J. Coord. Chem., 2021, vol. 47, p. 275. https://doi.org/10.1134/S1070328421040047

    Article  Google Scholar 

  26. Li, S., An, X.-X., Wang, J.-F., Wang, L., and Xue, L.-G., J. Struct. Chem., 2020, vol. 61, p. 1997, https://doi.org/10.1134/S0022476620120185

    Article  Google Scholar 

  27. Luo, X., Deng, X., Jing, Y.R., Wen, Y.W., and Yi, C.W., Russ. J. Gen. Chem., 2022, vol. 92, p. 1109. https://doi.org/10.1134/S1070363222060238

    Article  CAS  Google Scholar 

  28. Cano, R., Ramón, D.J., and Yus, M., J. Org. Chem., 2011, vol. 76, p. 654. https://doi.org/10.1021/jo1022052

    Article  CAS  Google Scholar 

  29. Wang, Z., Shi, J.T., Zhu, X.L., Zhao, W.W., Gong, Y.L., Hao, X.C., Hou, Y.L., Liu, Y.J., Ding, S., Liu, J., and Chen, Y., Bioorg. Chem., 2020, vol. 105, p. 104371. https://doi.org/10.1016/j.bioorg.2020.104371

  30. Han, X., Cai, Z.-Q., Wu, L.-H., Hou, L., and Li, S., Russ. J. Gen. Chem., 2021 vol. 91, p. 2286. https://doi.org/10.1134/S1070363221110165

    Article  CAS  Google Scholar 

  31. Wang, B., Cai, Z.-Q., Shi, X.-Y., Li, X., Li, S., and Li, J.-X., J. Chem. Soc. Pak., 2021, vol. 43, p. 466. https://doi.org/10.52568/000583/JCSP/43.04.2021

    Article  CAS  Google Scholar 

  32. Nemeth, J., Debreczeni, N., Gresits, I., Balint, M., and Hell, Z., Catal. Lett., 2015, vol. 145, p. 1113. https://doi.org/10.1007/s0562-015-1523-6

    Article  CAS  Google Scholar 

  33. Hanan, E.J., Baumgardner, M., Bryan, M.C., Yuan, C., and Heffron, T., Bioorg. Med. Chem. Lett., 2016, vol. 26, p. 534. https://doi.org/10.1016/j.bmcl.2015.11.078

    Article  CAS  Google Scholar 

  34. Zhang, X., Gureasko, J., Shen, K., Cole, P.A., and Kuriyan, J., Cell., 2006, vol. 125, p. 1137. https://doi.org/10.1016/j.cell.2006.05.013

    Article  CAS  Google Scholar 

  35. Daina, A., Michielin, O., and Zoete, V., J. Chem. Inf. Mod., 2014, vol. 54, p. 3284. https://doi.org/10.1021/ci500467k

    Article  CAS  Google Scholar 

  36. Lipinski, C.A., Lombardo, F.B., Dominy, W., and Feeney, P.J., Adv. Drug. Deliv. Rev., 2001, vol. 46, p. 3. https://doi.org/10.1016/j.addr.2012.09.019

    Article  CAS  Google Scholar 

  37. Veber, D.F., Johnson, S.R., Cheng, H.-Y., Smith, B.R., Ward, K.W., and Kopple, K.D., J. Med. Chem., 2002, vol. 45, p. 2615. https://doi.org/10.1021/jm020017n

    Article  CAS  Google Scholar 

  38. Lei, H.R., Wang, X.Y., Zhao, G.L., Li, T., Cui, Y.B., Wu, H.N., Yang, J., Jiang, N., and Zhai, X., Eur. J. Med. Chem., 2022, vol. 236, p. 114307. https://doi.org/10.1016/j.ejmech.2022.114307

    Article  CAS  Google Scholar 

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Funding

This work was financially supported by the Natural Science Foundation of Liaoning Province (no 20180550016), the Scientific Research Foundation of the Education Department of Liaoning Province (no. LJGD2020015).

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Authors and Affiliations

  1. Liaoning Province Professional and Technical Innovation Center for Fine Chemical Engineering of Aromatics Downstream, School of Petrochemical Engineering, Shenyang University of Technology, 111003, Liaoyang, China

    Liang-liang Chi, Lin-lin Hao, Zhi-qiang Cai, Ya-nan Wang, Wei-tao Qin, Yang Gao & Zhi-zhuo Qu

  2. Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hainan Medical University, 571199, Haikou, China

    Du-lin Kong

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  1. Liang-liang Chi
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Correspondence to Zhi-qiang Cai or Du-lin Kong.

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Chi, Ll., Hao, Ll., Cai, Zq. et al. Design, Synthesis, and Biological Evaluation of Novel Pyrazolo[1,5-a]pyrimidine and 1,3-Benzodiazine Derivatives as Potent Antitumor Agents. Russ J Gen Chem 92, 2698–2707 (2022). https://doi.org/10.1134/S1070363222120209

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