Research on Chemical Intermediates

, Volume 44, Issue 5, pp 3349–3364 | Cite as

Synthesis, antileishmanial and cytotoxicity activities of fused and nonfused tetrahydroquinoline derivatives

  • Hassan Mohamed Fawzy Madkour
  • Maher Abd El-Aziz Mahmoud El-Hashash
  • Marwa Sayed Salem
  • Al-Shimaa Omar Ali Mahmoud


Developing novel antileishmanial, and cytotoxic drugs has been a significant area in modern pharmaceutical research. A series of novel triazolo[4,3-a]quinoline, triazino[4,3-a]quinoline, thiadiazepino[5,6-b]quinoline and pyrazolquinoline have been synthesized from the reaction of 2-hydrazinyltetrahydroquinoline-3-carbonitrile with formamide, formic acid, ethyl chloroacetate, carbon disulphide in an alcoholic solution of potassium hydroxide acetyl acetone and/or ethyl cyanoacetate, respectively. These compounds were evaluated for their in vitro studies against L. major leishmanial. The brine shrimp bioassay was also conducted to study their in vitro cytotoxic properties which displayed potent cytotoxic activity against Vincristine. The newly synthesized compounds were all characterized through IR, 1H-NMR, and MS.


Tetrahydroquinolines Triazolo[4,3-a]quinoline Triazino[4,3-a]quinoline Thiadiazepino[5,6-b]quinoline Antileishmanial Cytotoxicity 



The authors gratefully thank Dr. Muhammad Ashfaq and Dr. Yasser MSA Alkahraman, Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan for performing antileishmanial and cytotoxicity screening of the synthesized compounds.


  1. 1.
    O.I. Abd El-Salam, D.A. Abou Ella, N.S. Ismail, M. Abdullah, Pharmazie 64(3), 147 (2009)Google Scholar
  2. 2.
    K. Tsuji, G.W. Spears, K. Nakamura, T. Tojo, N. Seki, A. Sugiyama, M. Matsuo, Bioorg. Med. Chem. Lett. 12(1), 85 (2002)CrossRefGoogle Scholar
  3. 3.
    I. Tomasoli, M. Pudlo, C. de Los Rios, E. Soriano, I. Colmena, L. Gandia, L. Rivas, A. Samadi, J. Marco-Contelles, B. Refouvelet, Eur. J. Med. Chem. 46, 1 (2011)CrossRefGoogle Scholar
  4. 4.
    M.M. Ghorab, F.A. Ragab, M.M. Hamed, Eur. J. Med. Chem. 44, 4211 (2009)CrossRefGoogle Scholar
  5. 5.
    S.I. Alquasoumi, A.M. Al-Taweel, A.M. Alafeefy, M.M. Ghorab, E. Noaman, Eur. J. Med. Chem. 45(5), 1849 (2010)CrossRefGoogle Scholar
  6. 6.
    N. Yamada, S. Kadowaki, K. Takahashi, K. Umezu, Biochem. Pharmacol. 44, 1211 (1992)CrossRefGoogle Scholar
  7. 7.
    D.S. Su, J.J. Lim, E. Tinney, B.L. Wan, M.B. Young, K.D. Anderson, D. Rudd, V. Munshi, C. Bahnck, Bioorg. Med. Chem. Lett. 19, 5119 (2009)CrossRefGoogle Scholar
  8. 8.
    R.T. Skerlj, G.J. Bridger, A. Kaller, E.J. McEachern, J.B. Crawford, Y. Zhou, J. Med. Chem. 53, 3376 (2010)CrossRefGoogle Scholar
  9. 9.
    C. Ramesh, T.K. Nayak, R. Burai, M.K. Dennis, H.J. Hathaway, L.A. Sklar, E.R. Prossnitz, J.B. Arterburn, J. Med. Chem. 53, 1004 (2010)CrossRefGoogle Scholar
  10. 10.
    H.F. de Freitas, M.S. Castilho, Med. Chem. 8(2), 252 (2012)CrossRefGoogle Scholar
  11. 11.
    T.A. Rano, E. Sieber-McMaster, P.D. Pelton, M. Yang, K.T. Demarest, G.H. Kuo, Bioorg. Med. Chem. Lett. 19, 2456 (2009)CrossRefGoogle Scholar
  12. 12.
    S. Prafulla, P. Pratik, K. Prabhjot, AJRC 6, 599 (2013)Google Scholar
  13. 13.
    H.S. Kim, H.J. Gim, M. Yang, J.H. Ryu, R. Jeon, Heterocycles 71, 2131 (2007)CrossRefGoogle Scholar
  14. 14.
    G. Dorey, B. Lockhart, P. Lestage, P. Casara, Bioorg. Med. Chem. Lett. 10, 935 (2000)CrossRefGoogle Scholar
  15. 15.
    D.K. Dodiya, H.K. Ram, A.R. Trivedi, V.H. Shah, J. Serb. Chem. Soc. 76(6), 823 (2011)CrossRefGoogle Scholar
  16. 16.
    H.M. Faidallah, A.A. Saqer, K.A. Alamry, K.A. Khan, A.M. Asiri, J. Enzyme Inhib. Med. Chem. 29(3), 367 (2014)CrossRefGoogle Scholar
  17. 17.
    H.M.F. Madkour, M.A.E.M. El-Hashash, M.S. Salem, A.O.A. Mahmoud, Y.M.A.S. Al-Qahraman, J. Heterocyclic Chem. (2017).
  18. 18.
    M.S. Salem, M.A.M. Ali, Biol. Pharm. Bull. 39, 473 (2016)CrossRefGoogle Scholar
  19. 19.
    M.S. Salem, M. Farhat, A.O. Errayes, H.M.F. Madkour, Chem. Pharm. Bull. 63, 866 (2015)CrossRefGoogle Scholar
  20. 20.
    M.S. Salem, A.O. Errayes, J. Chem. Res. 40, 299 (2016)CrossRefGoogle Scholar
  21. 21.
    M.S. Salem, S.I. Sakr, W.M. El-Senousy, H.M.F. Madkour, Arch. Pharm. Chem. Life Sci. 346, 766 (2013)CrossRefGoogle Scholar
  22. 22.
    I.H. Eissa, A.M. El-Naggar, M.A. El-Hashash, Bioorg. Chem. 67, 43 (2016)CrossRefGoogle Scholar
  23. 23.
    M. El-Kady, E.M.H. Abbas, M.S. Salem, A.F.M. Kassem, S.I. Abd, El-Moez. Res. Chem. Intermed. 42, 3333 (2016)CrossRefGoogle Scholar
  24. 24.
    K. Saito, S. Kambe, A. Sakurai, H. Midorikawa, Synthesis (1981).
  25. 25.
    D.R. Anderson, N.W. Stehle, S.A. Kolodziej, E.J. Reinhard, L.F. Lee, United States Patent Application 20040142978, July 22 (2004)Google Scholar
  26. 26.
    E.J. Reinhard, S.A. Kolodziej, D.R. Anderson, N.W. Stehle, W.F. Vernier, L.F. Lee, S.G. Hegde, United States Patent Application 20040127519, July 1 (2004)Google Scholar
  27. 27.
    M.H. Abdel-Lattif, M.I. Kobeasy, ShH Abdel-Hafez, Int. J. Basic Appl. Sci. 3(4), 433 (2014)CrossRefGoogle Scholar
  28. 28.
    Y.M. Al-Kahraman, H.M.F. Madkour, D. Ali, M. Yasinzai, Molecules 15, 660 (2010)CrossRefGoogle Scholar
  29. 29.
    G.S. Singh, Y.M.S.A. Al-Kahraman, D. Mpadi, M. Yasinzai, Bioorg. Med. Chem. Lett. 22, 5704 (2012)CrossRefGoogle Scholar
  30. 30.
    G.S. Singh, Y.M.S.A. Al-Kahraman, D. Mpadi, M. Yasinzai, Med. Chem. 10, 382 (2014)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Hassan Mohamed Fawzy Madkour
    • 1
  • Maher Abd El-Aziz Mahmoud El-Hashash
    • 1
  • Marwa Sayed Salem
    • 1
  • Al-Shimaa Omar Ali Mahmoud
    • 1
  1. 1.Synthetic Organic Chemistry Laboratory, Chemistry Department, Faculty of ScienceAin Shams UniversityAbbassia, CairoEgypt

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