Advertisement

Synthesis and exploration of in-silico and in-vitro α-glucosidase and α-amylase inhibitory activities of N-(3-acetyl-2-methyl-4-phenylquinolin-6-yl)arylamides

  • L. Jyothish Kumar
  • Y. Suresh
  • R. Rajasekaran
  • S. Rajeswara Reddy
  • V. Vijayakumar
Original Paper
  • 7 Downloads

Abstract

In a search for α-amylase and α-glucosidase inhibitors to treat type II diabetes, a new series of N-(3-acetyl-2-methyl-4-phenylquinolin-6-yl)arylamides were synthesized from 3-acetyl-2-methyl-4-phenylquinolines. Initially, nitro function of 1-(2-methyl-6-nitro-4-phenylquinolin-3-yl) ethanone was converted into the corresponding amine by grinding it with zinc dust and ammonium chloride (reducing agent) which in turn successfully converted into the N-(3-acetyl-2-methyl-4-phenylquinolin-6-yl) arylamides by treating it with coupling reagents such as EDC, HATU, and DCC. All the synthesized compounds were found to afford excellent yields with HATU, moderate in EDC, and very less in DCC and hence, HATU was considered as a suitable coupling reagent. These analogs are structurally characterized by NMR, NMR-DEPT, and HRMS. All the synthesized compounds were evaluated for in-silico and in-vitro α-glucosidase and α-amylase inhibitory activity using acarbose as standard and all the compounds showed positive results by in-silico and in-vitro α-amylase inhibition assay. Among the tested compounds, compound 5c and 5d in α-glucosidase as well as in α-amylase are found to have least binding energy value. These compounds found to form more stable ligand–receptor complex amongst other compounds. In addition, in experimental part, also the compounds 5c and 5d exhibited 56.90 ± 0.77% and 59.46 ± 0.61% of the higher potent α-glucosidase inhibitory activity with IC50 values 171.75 ± 3.95 µmol/mL and 171.67 ± 1.57 µmol/mL significantly (p < 0.05) compared to the remaining seven test samples. And similarly, the compound 5c and 5d possessed α-amylase inhibitory activity at a concentration of 100 µg/mL (55.42 ± 0.42% and 55.42 ± 1.14%) with IC50 values 138.92 ± 4.44 µmol/mL and 158.78 ± 2.34 µmol/mL.

Keywords

Arylamides Coupling reagents (EDC, DCC and HATU) Antidiabetic activity α-Amylase inhibition activity α-Glucosidase inhibition activity Docking studies 

Notes

Acknowledgements

Authors are thankful to the administration, VIT University, Vellore, India, for providing facilities to carry research work and also thankful to SIF-Chemistry for providing NMR facility. Authors are thankful to University of Hyderabad [Network resource centre (UGC-NRC)] for HRMS facility and also NMR facilities. The authors also thankful to the Division of Animal Biotechnology, Department of Biotechnology, School of Herbal Studies and Nature Sciences, Dravidian University. Author L. Jyothish Kumar is thankful to the VIT University for providing research associate ship.

Supplementary material

13738_2018_1580_MOESM1_ESM.doc (5.5 mb)
Supplementary material 1 (DOC 5656 KB)

References

  1. 1.
    B. Shori, J. Food. Drug. Anal. 23, 609–618 (2014)CrossRefGoogle Scholar
  2. 2.
    S.A. Adefegha, G. Oboh, O.M. Adefegha, A.A. Boligon, M.L. Athayde, J. Sci. Food Agric. 94, 2726–2737 (2014)CrossRefGoogle Scholar
  3. 3.
    Z. Gong, Y. Peng, J. Qiu, A. Cao, G. Wang, Z. Peng, Molecules 22, 1555–1566 (2017)CrossRefGoogle Scholar
  4. 4.
    S.R. Joshi, E. Standl, N. Tong, P. Shah, S. Kalra, R. Rathod, Expert Opin. Pharmacother. 16, 1959–1981 (2015)CrossRefGoogle Scholar
  5. 5.
    R. Pili. J. Chang, R.A. Partis, R.A. Mueller, F.J. Chrest, A. Passaniti, Cancer Res. 55, 2920–2926 (1995)Google Scholar
  6. 6.
    J. Rawlings, H. Lomas, A.W. Pilling, M.J.R. Lee, D.S. Alonzi, J.S.S. Rountree, S.F. Jenkinson, G.W.J. Fleet, R.A. Dwek, J.H. Jones, Chem. Bio. Chem. 10, 1101–1105 (2009)CrossRefGoogle Scholar
  7. 7.
    N. Zitzmann, A.S. Mehta, S. Carrouée, T.D. Butters, F.M. Platt, J. McCauley, B.S. Blumberg, R.A. Dwek, T.M. Block, Proc. Natl. Acad. Sci. USA 96, 11878–11882 (1999)CrossRefGoogle Scholar
  8. 8.
    A.K. Ghose, V.N. Viswanadhan, J.J. Wendoloski, J. Combinatorial Chem. 1, 55–68 (1999)CrossRefGoogle Scholar
  9. 9.
    A.A. Bekhit, O.A. El-Sayed, E. Aboulmagd, J.Y. Park, Eur. J. Med. Chem. 39, 249–255 (2004)CrossRefGoogle Scholar
  10. 10.
    L.M. Beal, B. Liu, W. Chu, K.D. Moeller, Tetrahedron 56, 10113–10125 (2000)CrossRefGoogle Scholar
  11. 11.
    C.A. Montalbetti, V. Falque, Tetrahedron 61, 10827–10852 (2005)CrossRefGoogle Scholar
  12. 12.
    L.C. Chan, B.G. Cox, J. Org. Chem. 72, 8863–8869 (2007)CrossRefGoogle Scholar
  13. 13.
    N. Kushwaha, R.M. Salini, K.S. Kushwaha, Int. J. Chem. Tech 3, 204–209 (2011)Google Scholar
  14. 14.
    V. Duraipandiyan, S. Ignacimuthu, J. Ethnopharmacol. 123, 494–498 (2009)CrossRefGoogle Scholar
  15. 15.
    S.R. Dorn, H. Vippagunta, C. Matile, J.L. Jaquet, R.G. Vennerstrom, Ridley, Biochem. Pharmacol. 55, 727–736 (1998)CrossRefGoogle Scholar
  16. 16.
    V.R. Shanbhag, A.M. Crider, R. Gokhale, A. Harpalani, R.M. Dick, J. Pharm. Sci. 81, 149–154 (1992)CrossRefGoogle Scholar
  17. 17.
    M. Andreani, A. Granaiola, A. Leoni, R. Locatelli, M. Morigi, Rambaldi, J. Med. Chem. 48, 3085–3089 (2005)CrossRefGoogle Scholar
  18. 18.
    W. Gao, J.Y. Kim, S.N. Chen, S.H. Cho, J. Choi, B.U. Jaki, Y. Jin, D.C. Lakin, E. Lee, S.Y. Lee, J.B. McAipline, J.G. Napolitano, S.G. Franzblau, J.W. Suh, G.F. Fauli, Org. Lett. 16, 6044–6047 (2014)CrossRefGoogle Scholar
  19. 19.
    D. Edmont, R. Rocher, C. Plisson, J. Chenault, Bioorg. Med. Chem. Lett. 10, 1831–1834 (2000)CrossRefGoogle Scholar
  20. 20.
    L. Jyothish Kumar, V. Vijayakumar, Res. Chem. Intermed. 21, 5691–5705 (2017)CrossRefGoogle Scholar
  21. 21.
    S. Bienert, A. Waterhouse, T.A. de Beer, G. Tauriello, G. Studer, L. Bordoli, T. Schwede, Nucleic Acids Res. 45, 313–319 (2017)CrossRefGoogle Scholar
  22. 22.
    G.M. Morris, R. Huey, W. Lindstrom, M.F. Sanne, R.K. Belew, D.S. Goodsell, A.J. Olson, J. Comput. Chem. 30, 2785–2791 (2009)CrossRefGoogle Scholar
  23. 23.
    M.J. Abraham, T. Murtola, R. Schulz, S. Páll, J.C. Smith, B. Hess, E. Lindahl, SoftwareX 1–2, 19–25 (2015)CrossRefGoogle Scholar
  24. 24.
    H.M. Berman, J. Westbrook, Z. Feng, G. Gilliand, T.N. Bhat, H. Weissig, I.N. Shindyaloy, P.E. Bourne, The protein data bank. Nucleic Acids Res. 28, 235–242 (2000)CrossRefGoogle Scholar
  25. 25.
    M. Kontoyianni, L.M. Mantzanidou, D.L. Hadjipavlou, J. Med. Chem. 47, 558–565 (2004)CrossRefGoogle Scholar
  26. 26.
    Y. Kim, Y.K. Jeong, M.H. Wang, W.Y. Lee, H.I. Rhee, Nutrition 21, 756–761 (2005)CrossRefGoogle Scholar
  27. 27.
    C. Hansawasdi, J. Kawabata, T. Kasai, Biosci. Biotechnol. Biochem. 64, 1041–1043 (2000)CrossRefGoogle Scholar

Copyright information

© Iranian Chemical Society 2019

Authors and Affiliations

  1. 1.Department of Chemistry, School of Advanced sciences, Centre for Organic and Medicinal ChemistryVIT UniversityVelloreIndia
  2. 2.Division of Animal Biotechnology, Department of Biotechnology, School of Herbal Studies and Naturo SciencesDravidian UniversityKuppamIndia
  3. 3.Department of BiotechnologyVIT UniversityVelloreIndia

Personalised recommendations