Skip to main content

Advertisement

SpringerLink
Log in

Synthesis, docking and ADME prediction of novel 1,2,3-triazole-tethered coumarin derivatives as potential neuroprotective agents

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

In an attempt to find potential neuroprotective agents, a series of novel 3-(1-((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl) methoxyimino) ethyl)-2H-chromen-2-one derivatives 6a–j were synthesized by using “click reaction” and evaluated for their in vitro neuroprotectivity and toxicity against H2O2-induced PC12 cell lines by using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction assay. Most of them exhibited moderate to good activity in which compound 6e was found to have significant protectivity with cell viability of 94.51 ± 0.68% at 50 µg/ml concentration and half-maximal effective concentration (EC50) value of 14.04 µg/ml against injured PC12 cell lines and low toxicity with half-maximal cytotoxic concentration (CC50) value of 544.88 µg/ml. Furthermore, molecular docking was carried out in order to understand plausible binding modes of novel derivatives with the active site of glycogen synthase kinase-3β enzyme, and the results were well complemented by the in vitro neuroprotective results against H2O2-induced PC12 cell lines. Additionally, in silico ADME properties showed drug likeness with good oral absorption and moderate blood–brain barrier permeability. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR, IR and LC–MS analyses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. G.C. Gonzalez-Munoz, M.P. Arce, M.G. Lopez, B. Lopez, C. Perez, M. Villarroya, M.G. Lopez, A.G. Garcia, S. Conde, M.I.R. Franco, Eur. J. Med. Chem. 45, 6152 (2010)

    Article  CAS  Google Scholar 

  2. D. Pratico, Trends Pharmacol. Sci. 29, 609 (2008)

    Article  CAS  Google Scholar 

  3. K.J. Barnham, C.L. Masters, A.I. Bush, Nat. Rev. Drug Discov. 3, 205 (2004)

    Article  CAS  Google Scholar 

  4. S.F. Wang, Y. Yin, X. Wu, F. Qiao, S. Sha, P.C. Lv, J. Zhao, H.L. Zhu, Bioorg. Med. Chem. 22, 5727 (2014)

    Article  CAS  Google Scholar 

  5. Q. Ji, Z. Ge, Z. Ge, K. Chen, H. Wu, X. Liu, Y. Huang, L. Yuan, X. Yang, F. Liao, Eur. J. Med. Chem. 108, 166 (2016)

    Article  CAS  Google Scholar 

  6. W. Zhang, Z. Li, M. Zhou, F. Wu, X. Hou, H. Luo, H. Liu, X. Han, G. Yan, Z. Ding, R. Li, Bioorg. Med. Chem. Lett. 24, 799 (2014)

    Article  CAS  Google Scholar 

  7. M.Z. Hassan, H. Osman, M.A. Ali, M.J. Ahsan, Eur. J. Med. Chem. 123, 236 (2016)

    Article  CAS  Google Scholar 

  8. T.O. Olomola, R. Klein, N. Mautsa, Y. Sayed, P.T. Kaye, Bioorg. Med. Chem. 21, 1964 (2013)

    Article  CAS  Google Scholar 

  9. L. Lei, Y.B. Xue, Z. Liu, S.S. Peng, Y. He, Y. Zhang, R. Fang, J.P. Wang, Z.W. Luo, G.M. Yao, J.W. Zhang, G. Zhang, H.P. Song, Y.H. Zhang, Sci. Rep. 5, 13544 (2015)

    Article  CAS  Google Scholar 

  10. M. Khoobi, S. Emami, G. Dehghan, A. Foroumadi, A. Ramazani, A. Shafiee, Arch. Pharm. Chem. Life Sci. 344, 588 (2011)

    Article  CAS  Google Scholar 

  11. E. Grimm, C. Brideau, N. Chauret, C. Chan, D. Delorme, Y. Ducharme, D. Ethier, J. Falgueyret, R. Friesen, J. Guay, P. Hamel, D. Riendeau, C.S. Breau, P. Tagari, Y. Girard, Bioorg. Med. Chem. Lett. 16, 2528 (2006)

    Article  CAS  Google Scholar 

  12. D.H. Dawood, R.Z. Batran, T.A. Farghaly, M.A. Khedr, M.M. Abdulla, Arch. Pharm. Chem. Life Sci. 348, 875 (2015)

    Article  CAS  Google Scholar 

  13. S. Manfredini, C.B. Vicentini, M. Manfrini, N. Bianchi, C. Rutigliano, C. Mischiati, R. Gambari, Bioorg. Med. Chem. 8, 2343 (2000)

    Article  CAS  Google Scholar 

  14. K. Lal, P. Yadav, A. Kumar, Med. Chem. Res. 25, 644 (2016)

    Article  CAS  Google Scholar 

  15. É. Bokor, T. Docsa, P. Gergely, L. Somsák, Bioorg. Med. Chem. 18, 1171 (2010)

    Article  CAS  Google Scholar 

  16. T.W. Kim, Y. Yong, S.Y. Shin, H. Jung, K.H. Park, Y.H. Lee, Y. Lim, K.Y. Jung, Bioorg. Chem. 59, 1 (2015)

    Article  Google Scholar 

  17. J.L. Kelley, C.S. Koble, R.G. Davis, E.W. McLean, F.E. Soroko, B.R. Coopert, J. Med. Chem. 38, 4131 (1996)

    Article  Google Scholar 

  18. P. Passannanti, P. Diana, F. Barraja, A. Mingoia, G. Lauria, Cirrincione. Heterocycles 48, 1229 (1998)

    Article  CAS  Google Scholar 

  19. N. Devender, S. Gunjan, S. Chhabra, K. Singh, V.R. Pasam, S.K. Shukla, A. Sharma, S. Jaiswal, S.K. Singh, Y. Kumar, J. Lal, A.K. Trivedi, R. Tripathi, R.P. Tripathi, Eur. J. Med. Chem. 109, 187 (2016)

    Article  CAS  Google Scholar 

  20. A.K. Jordao, P.P. Afonso, V.F. Ferreira, M.C.B.V. de Souza, M.C.B. Almeida, C.O. Beltrame, D.P. Paiva, S.M.S.V. Wardell, J.L. Wardell, E.R.T. Tiekink, C.R. Damaso, A.C. Cunha, Eur. J. Med. Chem. 44, 3777 (2009)

    Article  CAS  Google Scholar 

  21. M. Sun, J. Hu, X. Song, D. Wu, L. Kong, Y. Sun, D. Wang, Y. Wang, N. Chen, G. Lui, Eur. J. Med. Chem. 67, 39 (2013)

    Article  CAS  Google Scholar 

  22. A. Asadipour, M. Alipour, M. Jafari, M. Khoobi, S. Emami, H. Nadri, A. Sakhteman, A. Moradi, V. Sheibani, F.H. Moghadam, A. Shafiee, A. Foroumadi, Eur. J. Med. Chem. 70, 623 (2013)

    Article  CAS  Google Scholar 

  23. C. Hooper, R. Killick, S. Lovestone, J. Neurochem. 104(6), 1433 (2008)

    Article  CAS  Google Scholar 

  24. Mudasir Maqbool, Mohammad Mobashir, Nasimul Hoda, Eur. J. Med. Chem. 107, 63 (2016)

    Article  CAS  Google Scholar 

  25. G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell, A.J. Olson, J. Comput. Chem. 30, 2785 (2009)

    Article  CAS  Google Scholar 

  26. E. ter Haar, J.T. Coll, D.A. Austen, H.M. Hsiao, L. Swenson, J. Jain, Nat. Struct. Biol. 8, 593 (2001)

    Article  Google Scholar 

  27. E.F. Pettersen, T.D. Goddard, C.C. Huang et al., J. Comput. Chem. 25, 1605 (2004)

    Article  CAS  Google Scholar 

  28. Y. Zhao, M.H. Abraham, J. Lee, A. Hersey, N.C. Luscombe, G. Beek, B. Sherborne, I. Cooper, Pharm. Res. 19, 1446 (2002)

    Article  CAS  Google Scholar 

  29. G. Walkinshaw, C.M. Waters, Neuro Science 63, 975 (1994)

    CAS  Google Scholar 

  30. I.Z. Tao, X.F. Li, I.I. Zhang, J.Y. Tian, X.B. Li, X. Sun, X.F. Li, I. Jiang, X.J. Zhang, J.Z. Chen, PLoS ONE 6, 1 (2011)

    Google Scholar 

  31. H. Garn, H. Krause, V. Enzmann, K. Drassler, Immunol. Method 168, 253 (1994)

    Article  CAS  Google Scholar 

  32. S.M. Thom, R.W. Horobin, E. Seidler, M.R. Barer, Appl. Bacteriol. 74, 433 (1993)

    Article  CAS  Google Scholar 

  33. G. Vistoli, A. Pedretti, B. Testa, Drug Discov. Today 13(7–8), 285 (2008)

    Article  CAS  Google Scholar 

  34. C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeny, Adv. Drug Deliv. Rev. 23, 3 (1997)

    Article  CAS  Google Scholar 

  35. D.E. Clark, S.D. Pickett, Drug Discov. Today 5, 49 (2000)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

One of the authors (MAK) gratefully acknowledges UGC for providing financial assistance in the form of a BSR fellowship. Funding was provided by University Grants Commission (Grant No. F.25-1/2013-14 (BSR)/7-187/2007 (BSR)).

Author information

Authors and Affiliations

  1. Department of Chemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517 502, India

    Maddineni Aruna Kumari, Chunduri Venkata Rao, Settypalli Triloknadh & Nallapaneni Harikrishna

  2. Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517 502, India

    Chintha Venkataramaiah, Wudayagiri Rajendra, Daggupati Trinath & Yeguvapalli Suneetha

Authors
  1. Maddineni Aruna Kumari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunduri Venkata Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Settypalli Triloknadh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nallapaneni Harikrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chintha Venkataramaiah
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wudayagiri Rajendra
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daggupati Trinath
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yeguvapalli Suneetha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chunduri Venkata Rao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumari, M.A., Rao, C.V., Triloknadh, S. et al. Synthesis, docking and ADME prediction of novel 1,2,3-triazole-tethered coumarin derivatives as potential neuroprotective agents. Res Chem Intermed 44, 1989–2008 (2018). https://doi.org/10.1007/s11164-017-3210-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-017-3210-2

Keywords

Search

Navigation