Issue

Vol. 32 No. 5 (2020): Vol 32 Issue 5

Copyright (c) 2020 AJC

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives

P. Raghurama Shetty
Department of Studies and Research in Organic Chemistry, Tumkur University, Tumakuru-572103, India
https://orcid.org/0000-0003-0234-5662
G. Shivaraja
Department of Studies and Research in Organic Chemistry, Tumkur University, Tumakuru-572103, India
https://orcid.org/0000-0001-7545-4611
G. Krishnaswamy
Department of Studies and Research in Organic Chemistry, Tumkur University, Tumakuru-572103, India
https://orcid.org/0000-0002-2876-8690
K. Pruthviraj
Department of Studies and Research in Organic Chemistry, Tumkur University, Tumakuru-572103, India
https://orcid.org/0000-0002-1167-3783
Vivek Chandra Mohan
Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru-572103, India
S. Sreenivasa
Department of Studies and Research in Organic Chemistry, Tumkur University, Tumakuru-572103, India
https://orcid.org/0000-0003-1096-5837

Corresponding Author(s) : S. Sreenivasa

drsreenivasa@yahoo.co.in

Asian Journal of Chemistry, Vol. 32 No. 5 (2020): Vol 32 Issue 5

Abstract

In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

Keywords

Pfitzinger reaction 2-Phenyl-quinoline-4-carboxamide Bioactivity in silico ADME Molecular docking studies
Shetty, P. R., Shivaraja, G., Krishnaswamy, G., Pruthviraj, K., Mohan, V. C., & Sreenivasa, S. (2020). Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives. Asian Journal of Chemistry, 32(5), 1151–1157. Retrieved from https://asianpubs.org/index.php/ajchem/article/view/2492
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. A. Bishnoi, A.K. Tiwari, S. Singh, A. Sethi, C.M. Tripathi and B. Banerjee, Med. Chem. Res., 22, 3527 (2013); https://doi.org/10.1007/s00044-012-0333-2
  2. M.I. Mohamed, N.G. Kandile and H.T. Zaky, J. Heterocycl. Chem., 54, 35 (2015); https://doi.org/10.1002/jhet.2529
  3. R. Musiol, J. Jampilek, V. Buchta, L. Silva, H. Niedbala, B. Podeszwa, A. Palka, K. Majerz-Maniecka, B. Oleksyn and J. Polanski, Bioorg. Med. Chem., 14, 3592 (2006); https://doi.org/10.1016/j.bmc.2006.01.016
  4. B. Kalluraya and S. Sreenivasa, Il Farmaco, 53, 399 (1998); https://doi.org/10.1016/S0014-827X(98)00037-8
  5. M.A.S. Abdelwahid, T. Elsaman, M.S. Mohamed, S.A. Latif, M.M. Mukhtar and M.A. Mohamed, J. Chem., 2019, 2859637 (2019); https://doi.org/10.1155/2019/2859637
  6. X. Xu, J. Wang and Q. Yao, Bioorg. Med. Chem. Lett., 25, 241 (2015); https://doi.org/10.1016/j.bmcl.2014.11.065
  7. J.T. Madak, A. Bankhead, C.R. Cuthbertson, H.D. Showalter and N. Neamati, Pharmacol. Therap., 195, 111 (2019); https://doi.org/10.1016/j.pharmthera.2018.10.012
  8. S.A. El-Feky, Z.K. Abd El-Samii, N.A. Osman, J. Lashine, M.A. Kamel and H.Kh. Thabet, Bioorg. Chem., 58, 104 (2014); https://doi.org/10.1016/j.bioorg.2014.12.003
  9. L. Zhu, K. Luo, K. Li, Y. Jin and J. Lin, Bioorg. Med. Chem., 25, 5939 (2017); https://doi.org/10.1016/j.bmc.2017.09.004
  10. M.A. Massoud, S.A. El Bialy, W.A. Bayoumi and W.M. El Husseiny, Heterocycl. Commun., 20, 81 (2014); https://doi.org/10.1515/hc-2013-0163
  11. S.S. Bharadwaj, B. Poojary, S.M. Kumar, K. Byrappa, G.S. Nagananda, A.K. Chaitanya, K. Zaveri, N.S. Yarla, Y. Shiralgi, A.K. Kudva and B.L. Dhananjayad, New J. Chem., 41, 8568 (2017); https://doi.org/10.1039/C6NJ03913H
  12. A.M. El-Agrody and A.M. El-Agrody, ARKIVOC, 134 (2011) https://doi.org/10.3998/ark.5550190.0012.b12
  13. O. Afzal, S. Kumar, M.R. Haider, R. Kumar, M. Jaggi and S. Bawa, Eur. J. Med. Chem., 97, 871 (2015); https://doi.org/10.1016/j.ejmech.2014.07.044
  14. X. Wang, X. Xie, Y. Cai, X. Yang, J. Li, Y. Li, W. Chen and M. He, Molecules, 21, 340 (2016); https://doi.org/10.3390/molecules21030340
  15. Y. Erugu, B. Sangepu, B. Gandu, G. Anupoju and V.R. Jetti, World J. Pharm. Pharm. Sci., 3, 1612 (2014).
  16. H.M. Berman, T. Battistuz, T.N. Bhat, W.F. Bluhm, P.E. Bourne, K. Burkhardt, Z. Feng, G.L. Gilliland, L. Iype, S. Jain, P. Fagan, J. Marvin, D. Padilla, V. Ravichandran, B. Schneider, N. Thanki, H. Weissig, J.D. Westbrook and C. Zardecki, Acta Crystallogr. D Biol. Crystallogr., 58, 899 (2002); https://doi.org/10.1107/S0907444902003451
  17. V. Lamour, L. Hoermann, J.M. Jeltsch, P. Oudet and D. Moras, J. Biol. Chem., 277, 18947 (2002); https://doi.org/10.1074/jbc.M111740200.
  18. W.S. El-serwy, N.A. Mohamed, E.M. Kassem, K. Mahmoud and M.M. Mounier, Iran. J. Pharm. Res., 15, 179 (2016).
  19. F. Denizot and R. Lang, J. Immunol. Methods, 89, 271 (1986); https://doi.org/10.1016/0022-1759(86)90368-6
  20. T. Mosmann, J. Immunol. Methods, 65, 55 (1983); https://doi.org/10.1016/0022-1759(83)90303-4
  21. K. Wingen, J.S. Schwed, K. Isensee, L. Weizel, A. •ivkovic, D. Odazic and H. Stark, Bioorg. Med. Chem. Lett., 24, 2236 (2014); https://doi.org/10.1016/j.bmcl.2014.03.098
  22. G. Wu, D.H. Robertson, C.L. Brooks III and M. Vieth, J. Comput. Chem., 24, 1549 (2003); https://doi.org/10.1002/jcc.10306
  23. C.A. Lipinski, Drug Discov. Today Technol., 1, 337 (2004); https://doi.org/10.1016/j.ddtec.2004.11.007
  24. C.A. Lipinski, F. Lombardo, B.A. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); https://doi.org/10.1016/S0169-409X(00)00129-0
  25. B.D. Bax, P.F. Chan, D.S. Eggleston, A. Fosberry, D.R. Gentry, F. Gorrec, I. Giordano, M.M. Hann, A. Hennessy, M. Hibbs, J. Huang, E. Jones, J. Jones, K.K. Brown, C.J. Lewis, E.W. May, M.R. Saunders, O. Singh, C.E. Spitzfaden, C. Shen, A. Shillings, A.J. Theobald, A. Wohlkonig, N.D. Pearson and M.N. Gwynn, Nature, 466, 935 (2010); https://doi.org/10.1038/nature09197
  26. R.G. Kurumbail, A.M. Stevens, J.K. Gierse, J.J. McDonald, R.A. Stegeman, J.Y. Pak, D. Gildehaus, J.M. iyashiro, T.D. Penning, K. Seibert, P.C. Isakson and W.C. Stallings, Nature, 384, 644 (1996); https://doi.org/10.1038/384644a0
  27. V. Chandramohan, A. Kaphle, M. Chekuri, S. Gangarudraiah and G.B. Siddaiah, Adv. Virol., 2015, 972067 (2015); https://doi.org/10.1155/2015/972067
  28. R.B. Ravelli, B. Gigant, P.A. Curmi, I. Jourdain, S. Lachkar, A. Sobel and M. Knossow, Nature, 428, 198 (2004); https://doi.org/10.1038/nature02393
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 4 Download : 0