Article Sidebar

Download
PDF

Main Article Content

Abstract

A novel series of quinoline benzamide derivatives have been synthesized and screened for their anticancer activity against a breast cancer cell line (MDA-MB-231) by MTT assay method. All the synthesized compounds were confirmed by spectral characterization viz. FTIR, 1H & 13C NMR and MS. All the molecules demonstrated potency less than 35 μM and were better than standard cisplatin but not comparable to doxorubicin. Compound 3i (IC50 = 6.86 μM) exhibited better promising anti-breast cancer activity among various synthesized molecules and in addition, docking of compound 3i into kinesin spindle protein (KSP) active site was performed in order to predict the affinity and the orientation at the enzyme active site.

Keywords

Quinoline benzamides Anti-breast cancer agent Docking MDA-MB-231

Article Details

How to Cite
V. Rathod, S., W. Shinde, K., S. Kharkar, P., P. Shah, C., V. Ingle, A., A. Lotlikar, O., & N. Dandekar, S. (2020). Synthesis, Docking Studies and Biological Evaluation of Novel N-(2-(3-fluorophenyl)-quinolin-5-yl)benzamide Derivatives as Potent Anti-breast Cancer Agents. Asian Journal of Organic & Medicinal Chemistry, 5(2), 97–102. https://doi.org/10.14233/ajomc.2020.AJOMC-P249
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. B. Macedo, C.H. Kaschula, R. Hunter, J.A.P. Chaves, J.D. van der Merwe, J.L. Silva, T.J. Egan and Y. Cordeiro, Synthesis and Anti-Prion Activity Evaluation of Aminoquinoline Analogues, Eur. J. Med. Chem., 45, 5468 (2010); https://doi.org/10.1016/j.ejmech.2010.07.054
  2. M. Casagrande, N. Basilico, C. Rusconi, D. Taramelli and A. Sparatore, Synthesis, Antimalarial Activity and Cellular Toxicity of New Arylpyrrolyl-aminoquinolines, Bioorg. Med. Chem. Lett., 18, 6625 (2010); https://doi.org/10.1016/j.bmc.2010.08.001
  3. F. Clemence, O. Le Martret, F. Delevallee, J. Benzoni, A. Jouanen, S. Jouquey, M. Mouren and R. Deraedt, 4-Hydroxy-3-quinolinecarbox-amides with Antiarthritic and Analgesic Activities, J. Med. Chem., 31, 1453 (1988); https://doi.org/10.1021/jm00402a034
  4. K. Takeda, T. Terauchi, M. Hashizume, K. Shin, M. Ino, H. Shibata and M. Yonaga, Design, Synthesis, and Structure Activity Relationships of a Series of 2-Ar-8-methyl-5-alkylaminoquinolines as Novel CRF1 Receptor Antagonists, Bioorg. Med. Chem. Lett., 22, 5372 (2012); https://doi.org/10.1016/j.bmcl.2012.07.047
  5. L. Savegnago, A.I. Vieira, N. Seus, B.S. Goldani, M.R. Castro, E.J. Lenardão and D. Alves, Synthesis and Antioxidant Properties of Novel Quinoline-Chalcogenium Compounds, Tetrahedron Lett., 54, 40 (2013); https://doi.org/10.1016/j.tetlet.2012.10.067
  6. S.T. Hazeldine, L. Polin, J. Kushner, K. White, T.H. Corbett, J. Biehl and J.P. Horwitz, Part 3: Synthesis and Biological Evaluation of Some Analogs of the Antitumor Agents, 2-{4-[(7-chloro-2-quinoxalinyl)oxy]-phenoxy}propionic Acid and 2-{4-[(7-bromo-2-quinolinyl)oxy]phenoxy}-propionic acid, Bioorg. Med. Chem., 13, 1069 (2005); https://doi.org/10.1016/j.bmc.2004.11.034
  7. I. Briguglio, R. Loddo, E. Laurini, M. Fermeglia, S. Piras, P. Corona, P. Giunchedi, E. Gavini, G. Sanna, G. Giliberti, C. Ibba, P. Farci, P. La Colla, S. Pricl and A. Carta, Synthesis, Cytotoxicity and Antiviral Evaluation of New Series of Imidazo[4,5-g]quinoline and Pyrido[2,3-g]-quinoxalinone Derivatives, Eur. J. Med. Chem., 105, 63 (2015); https://doi.org/10.1016/j.ejmech.2015.10.002
  8. J. Fiorito, F. Saeed, H. Zhang, A. Staniszewski, Y. Feng, Y.I. Francis, S. Rao, D.M. Thakkar, S.-X. Deng, D.W. Landry and O. Arancio, Synthesis of Quinoline Derivatives: Discovery of a Potent and Selective Phosphodiesterase 5 Inhibitor for the Treatment of Alzheimer¢s Disease, Eur. J. Med. Chem., 60, 285 (2013); https://doi.org/10.1016/j.ejmech.2012.12.009
  9. N.D. Shashikumar, G. Krishnamurthy, H.S. Bhojyanaik, M.R. Lokesh and K.S. Jithendrakumara, Synthesis of New Biphenyl-Substituted Quinoline Derivatives, Preliminary Screening and Docking Studies, J. Chem. Sci., 126, 205 (2014); https://doi.org/10.1007/s12039-013-0541-4
  10. R. Nandhakumar, T. Suresh, A.L.C. Jude, V. Rajesh Kannan and P.S. Mohan, Synthesis, Antimicrobial Activities and Cytogenetic Studies of Newer Diazepinoquinoline Derivatives via Vilsmeier-Haack Reaction, Eur. J. Med. Chem., 42, 1128 (2007); https://doi.org/10.1016/j.ejmech.2007.01.004
  11. B.S. Holla, M. Mahalinga, M.S. Karthikeyan, B. Poojary, P.M. Akberali and N.S. Kumari, Synthesis, Characterization and Antimicrobial Activity of Some Substituted 1,2,3-Triazoles, Eur. J. Med. Chem., 40, 1173 (2005); https://doi.org/10.1016/j.ejmech.2005.02.013
  12. R.S. Upadhayaya, J.K. Vandavasi, R.A. Kardile, S.V. Lahore, S.S. Dixit, H.S. Deokar, P.D. Shinde, M.P. Sarmah and J. Chattopadhyaya, Novel Quinoline and Naphthalene Derivatives as Potent Antimycobacterial Agents, Eur. J. Med. Chem., 45, 1854 (2010); https://doi.org/10.1016/j.ejmech.2010.01.024
  13. S. Okten, O. Cakmak, R. Erenler, Ö. Yüce and S. Tekin, Simple and Conve-nient Preparation of Novel 6,8-Disubstituted Quinoline Derivatives and their Promising Anticancer Activities, Turk. J. Chem., 37, 896 (2013); https://doi.org/10.3906/kim-1301-30
  14. Y. Wang, J. Ai, Y. Wang, Y. Chen, L. Wang, G. Liu, M. Geng and A. Zhang, Synthesis and c-Met Kinase Inhibition of 3,5-Disubstituted and 3,5,7-Trisubstituted Quinolines: Identification of 3-(4-Acetylpiperazin-1-yl)-5-(3-nitrobenzylamino)-7-(trifluoromethyl)quinoline as a Novel Anticancer Agent, J. Med. Chem., 54, 2127 (2011); https://doi.org/10.1021/jm101340q
  15. M.M. Ghorab, F.A. Ragab and M.M. Hamed, Arzneimittelforschung, 60, 141 (2010); https://doi.org/10.1055/s-0031-1296263
  16. N.R. Gollapalli, Green Synthesis, Characterization and Anthelminthic Activity of Newer Quinoline Derivatives Containing Acridine Moiety, Asian J. Pharm. Clin. Res., 10, 377 (2017); https://doi.org/10.22159/ajpcr.2017.v10i9.17226
  17. N. Ahmed, K.G. Brahmbhatt, S. Sabde, D. Mitra, I.P. Singh and K.K. Bhutani, Synthesis and Anti-HIV Activity of Alkylated Quinoline 2,4-diols, Bioorg. Med. Chem., 18, 2872 (2010); https://doi.org/10.1016/j.bmc.2010.03.015
  18. N.M. Khalifa, M.A. Al-Omar, A.A.A. El-Galil and M.A. El-Reheem, Anti-inflammatory and Analgesic Activities of Some Novel Carbox-amides Derived from 2-Phenyl Quinoline Candidates, Biomed. Res., 28, 869 (2017).
  19. C. Fonseca-Berzal, F.A. Rojas Ruiz, J.A. Escario, V.V. Kouznetsov and A. Gómez-Barrio, In vitro Phenotypic Screening of 7-Chloro-4-amino-(oxy)quinoline Derivatives as Putative Anti-Trypanosoma cruzi Agents, Bioorg. Med. Chem. Lett., 24, 1209 (2014); https://doi.org/10.1016/j.bmcl.2013.12.071
  20. H.C. Polonini, R.M.P. Dias, I.O. Souza, K.M. Gonçalves, T.B.B. Gomes, N.R.B. Raposo and A.D. da Silva, Quinolines Derivatives as Novel Sunscreening Agents, Bioorg. Med. Chem. Lett., 23, 4506 (2013); https://doi.org/10.1016/j.bmcl.2013.06.046
  21. M.M. Ghorab and M.S. Alsaid, Anti-breast Cancer Activity of Some Novel Quinoline Derivatives, Acta Pharm., 65, 271 (2015); https://doi.org/10.1515/acph-2015-0030
  22. Y. Yang, L. Shi, Y. Zhou, H.-Q. Li, Z.-W. Zhu and H.-L. Zhu, Design, Synthesis and Biological Evaluation of Quinoline Amide Derivatives as Novel VEGFR-2 Inhibitors, Bioorg. Med. Chem. Lett., 20, 6653 (2010); https://doi.org/10.1016/j.bmcl.2010.09.014
  23. M. Narwal, H. Venkannagari and L. Lehtio, Structural Basis of Selective Inhibition of Human Tankyrases, J. Med. Chem., 55, 1360 (2012); https://doi.org/10.1021/jm201510p
  24. X.Y. Yu, J.M. Hill, G. Yu, Y. Yang, A.F. Kluge, D. Keith, J. Finn, P. Gallant, J. Silverman and A. Lim, A Series of Quinoline Analogues as Potent Inhibitors of C. albicans Prolyl tRNA Synthetase, Bioorg. Med. Chem. Lett., 11, 541 (2001); https://doi.org/10.1016/S0960-894X(00)00697-1