Synthesis, biological evaluation and molecular docking studies of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives

  • Lakshmi Narayana Sharma Konidena
  • Sathish Kumar Boda
  • Suresh Kumar Chettu
  • Kumaraswamy Sorra
  • Sreenivas Enaganti
  • Praveena Mukkavilli
  • N. S. Kameswara Rao
  • P. V. Anantha Lakshmi
  • Raghu Babu Korupolu
Article
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Abstract

A series of novel 2-(2-cyanophenyl)-N-phenylacetamide derivatives 3(a-u) were designed and synthesized via selective amidation of methyl-2-(2-cyanophenyl)acetates over amidine formation by using AlMe3 as catalyst in good yields. All the newly synthesized derivatives were well characterized by 1H NMR, 13C NMR, FTIR and HRMS spectral techniques. All the synthesized title compounds were evaluated for their in vitro anticancer activity against three cancer cell lines. Among all compounds, 3i (IC50 = 1.20 μM, IC50 = 1.10 μM), 3j (IC50 = 0.11 μM, IC50 = 0.18 μM), 3o (IC50 = 0.98 μM, IC50 = 2.76 μM) showed excellent inhibitory activity than the standard Etoposide (IC50 = 2.11 μM, IC50 = 3.08 μM) against MCF-7 and A-549 cell lines, respectively. Docking analysis of all the compounds with the human topoisomerase II revealed that the compound 3j fitted well in the active site pocket, showing the best docking score of 158.072 kcal/mol.

Keywords

N-phenylacetamide Trimethylaluminum Docking studies Anticancer activity 

Notes

Acknowledgements

The authors express their profound thanks to the management of GVK Biosciences Private Limited for financial support. We thank Dr. Sudhir Kumar Singh and Dr. Somesh Sharma and Dr. Krishna Reddy Valluru for their invaluable support and motivation.

References

  1. 1.
    A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, D. Forman, J. Clin. 61, 69 (2011)Google Scholar
  2. 2.
    G. Colombano, C. Travelli, U. Galli, A. Caldarelli, M.G. Chini, P.L. Canonico, G. Sorba, G. Bifulco, G.C. Tron, A.A. Genazzani, J. Med. Chem. 53, 616 (2010)CrossRefGoogle Scholar
  3. 3.
    V. Spana, A. Montalbano, A. Carbone, B. Parrino, P. Diana, G. Cirrincione, I. Castagliuolo, P. Brun, O.G. Issinger, S. Tisi, I. Primac, D. Vedaldi, A. Salvador, P. Barraja, Eur. J. Med. Chem. 74, 340 (2014)CrossRefGoogle Scholar
  4. 4.
    P. Diana, A. Carbone, P. Barraja, A. Montalbano, B. Parrino, A. Lopergolo, M. Pennati, N. Zaffaroni, G. Cirrincione, ChemMedChem 6, 1300 (2011)CrossRefGoogle Scholar
  5. 5.
    H. Adam, J. Janczak, S. Jonnala, A. Michal, B. Bogumil, Bioorg. Med. Chem. Lett. 22, 4697 (2012)CrossRefGoogle Scholar
  6. 6.
    M. Tisler, Heterocycles 20, 1591 (1983)CrossRefGoogle Scholar
  7. 7.
    C.L. Allen, J.M.J. Williams, Chem. Soc. Rev. 40, 3405 (2011)CrossRefGoogle Scholar
  8. 8.
    V.R. Pattabiraman, J.W. Bode, Nature 480, 471 (2011)CrossRefGoogle Scholar
  9. 9.
    E. Valeur, M. Bradley, Chem. Soc. Rev. 38, 606 (2009)CrossRefGoogle Scholar
  10. 10.
    B. Gnanaprakasam, D. Milstein, J. Am. Chem. Soc. 133, 1682 (2011)CrossRefGoogle Scholar
  11. 11.
    K.V.N.S. Srinivas, B. Das, J. Org. Chem. 68, 1165 (2003)CrossRefGoogle Scholar
  12. 12.
    J.H. Forsberg, V.T. Spaziano, T.M. Balasubramanian, G.K. Liu, S.A. Kinsley, C.A. Duckworth, J.J. Poteruca, P.S. Brown, J.L. Miller, J. Org. Chem. 52, 1017 (1987)CrossRefGoogle Scholar
  13. 13.
    A. Basha, M. Lipton, S.M. Weinreb, Tetrahedron Lett. 48, 4171 (1977)CrossRefGoogle Scholar
  14. 14.
    F. Bracher, J. Prakt. Chem. 341, 88 (1999)CrossRefGoogle Scholar
  15. 15.
    M. Kunishima, C. Kawachi, K. Hioki, K. Terao, S. Tani, Tetrahedron 57, 1551 (2001)CrossRefGoogle Scholar
  16. 16.
    A.K. Nezhad, B. Mokhtari, M.N.S. Rad, Tetrahedron Lett. 44, 7325 (2003)CrossRefGoogle Scholar
  17. 17.
    S.Y. Han, Y.A. Kim, Tetrahedron 60, 2447 (2004)CrossRefGoogle Scholar
  18. 18.
    C. Duangkamol, S. Jaita, S. Wangngae, W. Phakhodee, M. Pattarawarapan, RSC Adv. 5, 52624 (2015)CrossRefGoogle Scholar
  19. 19.
    C. Gunanathan, Y. Ben-David, D. Milstein, Science 317, 790 (2007)CrossRefGoogle Scholar
  20. 20.
    R.M. Al Zoubi, M. Olivier, D.G. Hall, Angew. Chem. Int. Ed. 47, 2876 (2008)CrossRefGoogle Scholar
  21. 21.
    H. Lundberg, F. Tinnis, S. Nicklas, H. Adolfsson, Chem. Soc. Rev. 43, 2714 (2014)CrossRefGoogle Scholar
  22. 22.
    N. Caldwell, P.S. Campbell, C. Jamieson, F. Potjewyd, I. Simpson, A.J.B. Watson, J. Org. Chem. 79, 9347 (2014)CrossRefGoogle Scholar
  23. 23.
    B. Le Bourdonnec, A.C. William, D.E. Roland, Sulfonylaminophenylacetamide derivatives and methods of their use. U.S. Patent 2004/254156, 16 Dec 2004Google Scholar
  24. 24.
    P. Skehn, R. Storeng, A. Scudiero, J. Monks, D. McMohan, D. Vistica, W.T. Jonathan, H. Bokesch, S. Kenney, R.M. Boyd, J. Natl Cancer Inst. 82, 1107 (1990)CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Lakshmi Narayana Sharma Konidena
    • 1
    • 2
  • Sathish Kumar Boda
    • 3
  • Suresh Kumar Chettu
    • 1
    • 2
  • Kumaraswamy Sorra
    • 1
  • Sreenivas Enaganti
    • 4
  • Praveena Mukkavilli
    • 1
  • N. S. Kameswara Rao
    • 5
  • P. V. Anantha Lakshmi
    • 3
  • Raghu Babu Korupolu
    • 2
  1. 1.GVK Biosciences Private LimitedMedicinal Chemistry LaboratoryHyderabadIndia
  2. 2.Andhra University, Department of Engineering ChemistryAndhra University College of Engineering (A)VisakhapatnamIndia
  3. 3.Department of ChemistryOsmania UniversityTarnaka, HyderabadIndia
  4. 4.Department of BioinformaticsAverin Biotech Pvt. LtdHyderabadIndia
  5. 5.Koneru Lakshmaiah Education FoundationDeemed to be UniversityVaddeswaram, GunturIndia

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