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Synthesis of Some Hybrid 7-Hydroxy Quinolinone Derivatives As Anti Breast Cancer Drugs

  • Amal Mahmoud Youssef MoustafaEmail author
  • Safyah B. Bakare
Article
  • 32 Downloads

Abstract

A new series of hybrid 2-Quinolinone derivatives were synthesized and structurally proved using spectral and elemental analyses data. All the prepared compounds were tested for their in vitro cytotoxic activity against MCF-7 cell line. Compounds 6 and 8 showed potent anticancer activity, which were comparable to Doxorubicin as reference compound. While compound 3 was comparable to cisplatin. Cell cycle analysis of compounds 6 and 8 showed cell cycle arrest at S and G2/M phases of the cycle and induced apoptosis at pre-G1 phase. DNA synthesis inhibitory activity demonstrated that compound 6 showed equipotent activity to Doxorubicin. The extent of apoptosis was also determined using Annexin V-FITC assay. In addition, compounds 6 and 8 increase the activation of effector caspase 3 by four fold more than untreated control. On the other hand, the localization of compounds 3, 6 and 8 were found in the nucleus.

Keywords

Mass spectrometry (MS) Infrared (IR) spectroscopy Cancer Cell line 

Notes

Supplementary material

11164_2019_3827_MOESM1_ESM.docx (323 kb)
Supplementary material 1 (DOCX 323 kb)

References

  1. 1.
    J.J. Walsh, A. Bell, Curr. Pharm. Des. 15, 2970 (2009)CrossRefGoogle Scholar
  2. 2.
    F.W. Muregi, A. Ishih, Drug Dev. Res. 71, 20 (2010)Google Scholar
  3. 3.
    B. Meunier, in Polypharmacology in Drug Discovery, Jens-Uwe Peters Ed. (Wiley, New York, 2012), p. 423Google Scholar
  4. 4.
    B. Gervais, J. Expert Opin. Drug Discov. 11, 281 (2016)CrossRefGoogle Scholar
  5. 5.
    N.P. Peet, Drug Discov. Today 15, 583 (2010)CrossRefGoogle Scholar
  6. 6.
    N. Vetrivel, T.S. Senniappan, S. Raju, Arkivoc 10, 82 (2006)Google Scholar
  7. 7.
    P. Karel, K. Stanislav, K. Janez, Curr. Org. Chem. 21, 1949 (2017)Google Scholar
  8. 8.
    D.F. Matías, T.N. Alexandre, F.M. Ademir, S.K. Teodoro, L.L. Enrique, Eur. J. Med. Chem. 81, 253 (2014)CrossRefGoogle Scholar
  9. 9.
    M.M. Ghorab, M.S. Alsaid, Acta Pharm. 65(3), 271 (2015)CrossRefGoogle Scholar
  10. 10.
    C. Yi-Fong, L. Yi-Chien, L.M. Susan, W. Chen-Fang, S. Ting-Chen, L. Hui-Yi, H. Mei-Hua, C. Li-Chen, Z. Yu, K. Sheng-Chu, L. Kuo-Hsiung, H. Li-Jiau, Br. J. Pharmacol. 172, 1195 (2015)CrossRefGoogle Scholar
  11. 11.
    K. Suresh, B. Sandhya, G. Himanshu, Mini-Rev. Med. Chem. 9, 1648 (2009)CrossRefGoogle Scholar
  12. 12.
    G. Verma, A. Marella, M. Shaquiquzzaman, M. Akhtar, M.R. Ali, M.M. Alam, J. Pharm. Bioall. Sci. 6, 69 (2014)CrossRefGoogle Scholar
  13. 13.
    S. Patil, M.M. Kuman, S. Palvai, P. Sengupta, S. Basu, ACS Omega 3, 1470 (2018)CrossRefGoogle Scholar
  14. 14.
    R.I. Al-Bayati, M.R. Ahamad, L.S. Ahamed, Amer. J. Org. Chem. 5(4), 125 (2015)Google Scholar
  15. 15.
    A.A.M. Fenjan, I.S. Mahdi, S.A. Yousif, Int. J. Sci. Res. 6(3), 2319 (2017)Google Scholar
  16. 16.
    M. Bingul, O. Tan, C.R. Gardner, S.K. Sutton, G.M. Arndt, G.M. Marshall, B.B. Cheung, N. Kumar, D.S. Black, Molecules 21, 916 (2016)CrossRefGoogle Scholar
  17. 17.
    S.H. Chan, C.H. Chui, S.W. Chan, S.H.L. Kok, D. Chan, M.Y.T. Tsoi, P.H.M. Leung, A.K.Y. Lam, A.S.C. Chan, K.H. Lam, J.C.O. Tang, ACS Med. Chem. Lett. 4, 170 (2013)CrossRefGoogle Scholar
  18. 18.
    W. Linlin, H. Chen, S. Longquan, Int. J. Nanomed. 12, 1227 (2017)CrossRefGoogle Scholar
  19. 19.
    L. Imsang, C.D. Ken, M.B. James, Nucleic Acids Res. 41(10), 5444 (2013)CrossRefGoogle Scholar
  20. 20.
    S. Elmores, Toxicol. Pathol. 35(4), 495 (2007)CrossRefGoogle Scholar
  21. 21.
    F.Z. Mohamed, M.S. Elghreeb, M.S. Abdelhamid, H.A. Elbaz, AJRB 3(3), 1 (2019)Google Scholar
  22. 22.
    S. Bondock, A.E.-G. Tarhoni, A.A. Fadda, Monatshefte für Chemie 139, 153 (2008)Google Scholar
  23. 23.
    S. Bondock, A.E.-G. Tarhoni, A.A. Fadda, Arkivoc ix, 113 (2006)Google Scholar
  24. 24.
    T. Besson, C.W. Rees, D.G. Roe, V. Thiér, J. Chem. Soc., Perkin Trans. 1, 555 (2000)Google Scholar
  25. 25.
    S. Bondock, A.E.-G. Tarhoni, A.A. Fadda, J. Heterocyclic Chem. 52, 1792 (2015)CrossRefGoogle Scholar
  26. 26.
    N.P. Dattatraya, N.S. Rohini, D.P. Chandrakant, Lett. Org. Chem. 14(7), 517 (2017)Google Scholar
  27. 27.
    I.V. Ukrainets, A.A. Tkach, L.V. Sidorenko, O.V. Gorokhova, Chem. Heterocycl. Compd. 42, 10 (2006)Google Scholar
  28. 28.
    J. Han, T.P.N. Talorete, P. Yamada, H. Isoda, Cytotechnology 59, 45 (2009)CrossRefGoogle Scholar
  29. 29.
    T. Slater, B. Sawyer, U. Sträuli, Biochim. Biophys. Acta 77, 383 (1963)CrossRefGoogle Scholar
  30. 30.
    T. Mosmann, J. Immunol. Methods 65(1–2), 55 (1983)CrossRefGoogle Scholar
  31. 31.
    K. Likhitwitayawuid, C.K. Angerhofer, H. Chai, J.M. Pezzuto, G.A. Cordell, N. Ruangrungsi, J. Nat. Prod. 56(9), 1468 (1993)CrossRefGoogle Scholar
  32. 32.
    A. Barakat, M.S. Islam, H.M. Ghawas, A.M.Al-Majid, F.F. El-Senduny, F.A. Badria, Y.A.M. Elshaier, H.A. Ghabbour, R.S.C. Advances 8(26), 14335 (2018)Google Scholar
  33. 33.
    F.-F. Feng, D.-R. Zhang, K.-L. Tian, H.-Y. Lou, X.-L. Qi, Y.-C. Wang, C.-X. Duan, L.-J. Jia, F.-H. Wang, Y. Liu, Q. Zhang, Drug Deliv. 18(4), 265 (2011)CrossRefGoogle Scholar
  34. 34.
    C. Weidner, M. Rousseau, A. Plauth, S. Wowro, C. Fischer, H. Abdel-Aziz, S. Sauer, Phytomedicine 22, 262 (2015)CrossRefGoogle Scholar
  35. 35.
    G. Koopman, C.P.M. Reutelingsperger, G.A.M. Kuijten, R.M.J. Keehnen, S.T. Pals, M.H. van Oers, Blood 84(5), 1415 (1994)Google Scholar
  36. 36.
    L. Cai, W. Li, G. Wang, L. Guo, Y. Jiang, Y.J. Kang, Diabetes 51, 1938 (2002)CrossRefGoogle Scholar
  37. 37.
    M. Rams-Baron, M. Dulski, A. Mrozek-Wilczkiewicz, M. Korzec, W. Cieslik, E. Spaczynska, P. Bartczak, A. Ratuszna, J. Polanski, R. Musiol, PLoS ONE 10(6), e0131210 (2015)CrossRefGoogle Scholar
  38. 38.
    P.P. Dr. Alka, K.V. Sanjay, Int. J. Theor. Appl. Sci. 10(1), 40 (2018)Google Scholar
  39. 39.
    V.F. Traven, Molecules 9, 50 (2004)CrossRefGoogle Scholar
  40. 40.
    I. Zaki, M.K. Abdelhameid, I.M. El-Deen, A.H.A. Abdel Wahab, A.M. Ashmawy, K.O. Mohamed, Eur. J. Med. Chem. 156, 563 (2018)Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Amal Mahmoud Youssef Moustafa
    • 1
    Email author
  • Safyah B. Bakare
    • 2
  1. 1.Chemistry Department, Faculty of SciencePort Said UniversityPort SaidEgypt
  2. 2.Faculty of EducationShaqra UniversityAlmuzahimiyahKingdom of Saudi Arabia

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