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Novel Furochromone Derivatives of Potential Anticancer Activity Targeting EGFR Tyrosine Kinase. Synthesis and Molecular Docking Study


In this study, a new class of furochromone derivatives bearing β-naphthol was synthesized via one-pot multicomponent reactions. First, condensation one mole of furochromone carbaldehyde (I) with two moles of β-naphthol afforded the corresponding Xanthene’ dye derivatives (II). A one-pot three-component reaction of (I), β-naphthol and urea or thiourea result in the formation of the corresponding oxazinones (IIIa, b). Moreover, reaction of (I) and β-naphthol with primary aromatic amines, heterocyclic amines or 2ry amines using triethyl amine as catalyst afforded the corresponding amino derivatives (IVXIII). On the other hand, a one-pot three-component reaction of (I) and β-naphthol with active methylene compounds namely, malononitrile, propionitrile, diethylmalonate methyl propionate or diethyl succinate led to the formation of furochromone derivatives (VIV)–(XVIII). The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of three (liver, HepG2; breast, MCF-7, HepG-2 and PC-3) human solid tumor cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drug: 5-fluorouracil using MTT assay. Our results showed that the vast majority of the newly synthesized derivatives did not exert any activity against the growth of HFB4normal cell line. Compounds (IV), (XIIIa), and (XIIIb) revealed remarkable anticancer activity against MCF-7 cell line with IC50 5.4, 4.65, and 6.09 μg/mL respectively compared to 5-fluorouracil (IC50 = 4.7 μg/mL). Moreover, compounds (IIIb), (VII), (IX), and (XVI) showed potent activity against HepG-2 cancer cell line of IC50 ranging from 5.57 to 6.34 μg/mL. Compound (VII) revealed also anticancer activity against PC-3 cancer cell line with IC50 6.77 μg/mL vs. 5.05 for 5-fluorouracil. The inhibitory activity of the most active anti-proliferative compounds (IIIb), (IV), (VII), (IX), (XIIIa, b) and (XVI) against EGFR were studied. Compound (VII) showed the best inhibitory activity against EGFR with IC50 39.93 ng/ml in comparison to erlotinib (IC50 29.18 ng/mL). Molecular docking simulation was performed to position compounds (IIIb), (IV), (VII), (IX), (XIIIa, b), and (XVI) into the EGFR active site to determine the probable binding mode.

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  1. Cooper, G.M., The Cell: A Molecular Approach, Sunderland, MA: Sinauer Associates, The Development and Causes of Cancer, 2000, 2nd ed. https://www.ncbi.

    Google Scholar 

  2. Schirrmacher, V., Int. J. Oncol., 2019, vol. 54, pp. 407–419.

    CAS  Article  PubMed  Google Scholar 

  3. Szumilak, M., Wiktorowska-Owczarek, A., and Stanczak, A., Molecules, 2021, vol. 26, p. 2601.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Elgazwy, A.S.H., Edrees, M.M., and Ismail, N.S.M., J. Enzyme Inhib. Med. Chem., 2013, vol. 28, pp. 1171–1181.

    CAS  Article  PubMed  Google Scholar 

  5. Le, Y., Gan, Y., Fu, Y., Liu, J., Li, W., Zou, X., Zhou, Z., Wang, Z., Ouyang, G., and Yan, L., J. Enzyme Inhib. Med. Chem., 2020, vol. 35, pp. 555–564.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Chang, S.C., Lai, Y.C., Chang, C.Y., Huang, L.K., Chen, S.J., Tan, K.T., Yu, P.N., and Lai, J.I., Transl. Oncol., 2019, vol. 12, pp. 1425–1431.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gan, Y., Shi, C., Inge, L., Hibner, M., Balducci, J. and Huang. Y., Oncogene, 2010, vol. 29, pp. 4947–4958.

    CAS  Article  PubMed  Google Scholar 

  8. Barker, A.J., Gibson, K.H., Grundy, W., Godfrey, A.A., Barlow, J.J., Healy, M.P., Woodburn, J.R., Ashton, S.E., Curry, B.J., Scarlett, L., Henthorn, L. and Richards, L., Bioorg. Med. Chem. Lett., 2001, 11, 1911–1914.

    CAS  Article  PubMed  Google Scholar 

  9. Higgins, B., Kolinsky, K., Smith, M., Beck, G., Rashed, M., Adames, V., Linn, M., Wheeldon E, Gand, L., Birnboeck, H., and Hoffmann, G., Anticancer Drugs, 2004, vol. 15, pp. 503–512.

    CAS  Article  PubMed  Google Scholar 

  10. Sequist, L. V., Waltman, B.A., Dias-Santagata, D., Digumarthy, S., Turke, A.B., Fidias, P., Bergethon, K., Shaw, A.T., Gettinger, S., Cosper, A.K., Akhavanfard, S., Heist, R.S., Temel, J., Christensen, J.G., Wain, J.C., Lynch, T.J., Vernovsky, K., Mark, E.J., Lanuti, M., Iafrate, A.J., Mino-Kenudson, M., and Engelman, J.A., Sci. Translat. Med., 2011, vol. 3, pp. 75–101.

    Article  Google Scholar 

  11. Thress, K.S., Paweletz, C.P., Felip, E., Cho, B.C., Stetson, D., Dougherty, B., Lai, Z., Markovets, A., Vivancos, A., Kuang, Y., Ercan, D., Matthews, S.E., Cantarini, M., Barrett, J.C., Jänne, P.A. and Oxnard, G.R., Nat. Med., 2015, vol. 21, pp. 560–562.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Franchi, G.G., Bovalini, L., Martelli, P., Ferri, S. and Sbardellati, E., J. Ethnopharmacol., 1985, vol. 14, pp. 203–212.

    CAS  Article  PubMed  Google Scholar 

  13. Ullrich, A. and Schlessinger, J., Cell, 1990, vol. 61, pp. 203–212.

    CAS  Article  PubMed  Google Scholar 

  14. Hubbard, S.R. and Till, J.H., Annu. Rev. Biochem., 2000, vol. 69, pp. 373–398.

    CAS  Article  PubMed  Google Scholar 

  15. Dai, Y., Guo, Y., Frey, R.R., Ji, Z., Curtin, M.L., Ahmed A.A., Albert, D.H., Arnold, L., Arries S.S., Barlozzari, T., Bauch, J.L., Bouska, J.J., P.F. Bousquet, Cunha, G.A., Glaser, K.B., Guo, J., Li, J., Marcotte, P.A., Marsh, K.C., Moskey, M.D., Pease, L.J., Stewart, K.D., Stoll,V.S., Tapang, P., Wishart, N., Davidsen, S.K., and Michaelides, M.R. J. Med. Chem., 2005, vol. 48, pp. 6066–6083.

    CAS  Article  PubMed  Google Scholar 

  16. Chaudhary, A., Mol. Diversity, 2021, vol. 25, pp. 1211–1245.

    CAS  Article  Google Scholar 

  17. Nishiyama, T., Sakita, K., Fuchigami, T., and Tsutomu, F.T., Polym. Degrad. Stab., 1998, vol. 62, pp. 529–534.

    CAS  Article  Google Scholar 

  18. Zelefack, F., Guilet, D., Fabre, N., Bayet, C., Chevalle, S., Ngouela, S., Lenta, B. N., Valentin, A., Tsamo, E., and Dijoux-Franca, M.G., J. Nat. Prod., 2009, vol. 72, pp. 954–957.

    CAS  Article  Google Scholar 

  19. Wan, Y., Wang, C., Wang, H., Zhao, L., Zhang, X., Shi, J., and Wu, H., J. Heterocycl. Chem., 2014, vol. 51, pp. 1293–1297.

    CAS  Article  Google Scholar 

  20. Bhattacharjee, S., Gattu, R., and Khan, A.T., Chem. Select., 2018, vol. 3, pp. 4760–4763.

    CAS  Article  Google Scholar 

  21. Devi, K.M., Chanu, L.G., Chanu, I.S., and Singh, O.M., Lett. Org. Chem., 2014, vol. 11, pp. 743–747.

    CAS  Article  Google Scholar 

  22. Mathew, B.P., Kumar, A., Sharma, S., and Shukla, P.K., Eur. J. Med. Chem., 2010, vol. 45, pp. 1502–1507.

    CAS  Article  PubMed  Google Scholar 

  23. Vahabinia, H.R., Karami, B., and Khodabakhshi, S., J. Chin. Chem. Soc., 2013, vol. 60, pp. 1323–1327.

    CAS  Article  Google Scholar 

  24. Singh, M., Nandi, G., and Samai, S., Synlett., 2010, vol. 7, pp. 1133–1137.

    CAS  Article  Google Scholar 

  25. Zhi, S., Ma, X., and Zhang, W., Org. Biomol. Chem., 2019, vol. 17, pp. 7632–7650.

    CAS  Article  PubMed  Google Scholar 

  26. Barra, I.A., Islas-Jácome, A., and González-Zamora, E., Org. Biomol. Chem., 2018, vol. 16, pp. 1402–1418.

    CAS  Article  Google Scholar 

  27. Shabir, G. and Saeed, A., J. Chil. Chem. Soc., 2016, vol. 61, pp. 2907–2912.

    CAS  Article  Google Scholar 

  28. Cardellicchio, C., Capozzi, M.A.M., and Naso, F., Tetrahedron, 2010, vol. 21, pp. 507–517.

    CAS  Article  Google Scholar 

  29. Stamos, J., Sliwkowski, M.X., and Eigenbrot, C., J. Biol. Chem., 2002, vol. 277, pp. 46265–46272.

    CAS  Article  PubMed  Google Scholar 

  30. Raymond, E., Faivre, S., and Armand, J.P., Drugs, 2000, vol. 60, pp. 15–23.

    CAS  Article  PubMed  Google Scholar 

  31. Nakamura, J.L., Expert Opin. Ther. Targets, 2007, vol. 11, pp. 463–472.

    CAS  Article  PubMed  Google Scholar 

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The authors are grateful to Dr. Esam Rashwan, Head of the confirmatory diagnostic unit VACSERA-EGYPT, for carrying out the enzyme assays.

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Correspondence to H. M. Abo-Salem.

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This article does not contain any studies involving human participants performed by any of the authors and does not contain any studies involving animals performed by any of the author.

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Fawzy, N.M., Ahmed, K.M., Abo-Salem, H.M. et al. Novel Furochromone Derivatives of Potential Anticancer Activity Targeting EGFR Tyrosine Kinase. Synthesis and Molecular Docking Study. Russ J Bioorg Chem 48, 749–767 (2022).

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  • furochromones
  • β-napthol
  • anticancer activity
  • docking
  • EGFR tyrosine kinase