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Abstract

In search of new anticancer agents with improved efficacy, we designed and synthesized novel hybrid series of isonicotinamide and diaryl urea motifs (R1-R9). Design of series compounds carried out using docking study by Autodock vina tool. Binding energy (more than -9.7 kcal/mol) calculated using Autodock vina against Raf kinase (PDB: 4DBN). All the synthesized compounds were evaluated for them in vitro anticancer activity against MCF-7 cell line. The anticancer activities of the synthesized compounds were also carried. Some of the compounds (R1, R8, R9) showed better activities towards MCF-7 cell line by MTT assay.

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Isonicotinamide Diaryl urea Molecular docking Anticancer MTT assay.

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Copyright (c) 2022 Asian Journal of Organic & Medicinal Chemistry

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Marvaniya, V., V. Joshi, H., A. Shah, U., & K. Patel, J. (2022). Synthesis, Anticancer Evaluation and Molecular Docking Studies of Isonicotinamide and Diaryl Urea Hybrid Motifs. Asian Journal of Organic & Medicinal Chemistry, 7(2), 179–186. https://doi.org/10.14233/ajomc.2022.AJOMC-P382
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References

  1. L. Garuti, M. Roberti, G. Bottegoni and M. Ferraro, Diaryl Urea: A Privileged Structure in Anticancer Agents, Curr. Med. Chem., 23, 1528 (2016); https://doi.org/10.2174/0929867323666160411142532
  2. J.X. Qiao, T.C. Wang, R. Ruel, C. Thibeault, A. L’Heureux, W.A. Schumacher, S.A. Spronk, S. Hiebert, G. Bouthillier, J. Lloyd, Z. Pi, D.M. Schnur, L.M. Abell, J. Hua, L.A. Price, E. Liu, Q. Wu, T.E. Steinbacher, J.S. Bostwick, M. Chang, J. Zheng, Q. Gao, B. Ma, P.A. McDonnell, C.S. Huang, R. Rehfuss, R.R. Wexler and P.Y.S. Lam, Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1¢-Neopentylspiro[indoline-3,4¢-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, A Potent, Selective, and Bioavailable P2Y1 Antagonist, J. Med. Chem., 56, 9275 (2013); https://doi.org/10.1021/jm4013906
  3. J. Anderson, D. Sarantakis, J. Terpinski, T.R. Santha Kumar, H.-C. Tsai, M. Kuo, A.L. Ager, W.R. Jacobs Jr., G.A. Schiehser, S. Ekins, J.C. Sacchettini, D.P. Jacobus, D.A. Fidock and J.S. Freundlich, Novel Diaryl Ureas with Efficacy in a Mouse Model of Malaria, Bioorg. Med. Chem. Lett., 23, 1022 (2013); https://doi.org/10.1016/j.bmcl.2012.12.022
  4. A.P. Keche, G.D. Hatnapure, R.H. Tale, A.H. Rodge and V.M. Kamble, Synthesis, Anti-inflammatory and Antimicrobial Evaluation of Novel 1-Acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazole Derivatives bearing Urea, Thiourea and Sulfonamide Moieties, Bioorg. Med. Chem. Lett., 22, 6611 (2012); https://doi.org/10.1016/j.bmcl.2012.08.118
  5. R.G. Kulkarni, S. Laufer, C. Mangannavar and A. Garlapati, Design, Synthesis and Characterization of N¢,N¢-Diaryl Ureas as p38 Kinase Inhibitors, Med. Chem., 9, 213 (2013); https://doi.org/10.2174/1573406411309020006
  6. F. Hassanzadeh, S. Sadeghian-Rizi, G. Khodarahmi, A. Sakhteman, A. Jahanian-Najafabadi, M. Rostami and M. Mirzaei, Synthesis and Characterization of Some Novel Diaryl Urea Derivatives Bearing Quinoxalindione Moiety, Res. Pharm. Sci., 13, 82 (2018); https://doi.org/10.4103/1735-5362.220971
  7. A.K. Ghosh and M. Brindisi, Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry, J. Med. Chem., 63, 2751 (2020); https://doi.org/10.1021/acs.jmedchem.9b01541
  8. A. Catalano, D. Iacopetta, M.S. Sinicropi and C. Franchini, Diarylureas as Antitumor Agents, Appl. Sci., 11, 374 (2021); https://doi.org/10.3390/app11010374
  9. S.H. Tella, A. Kommalapati and A. Mahipal, Systemic Therapy for Advanced Hepatocellular Carcinoma: Targeted Therapies, Chin. Clin. Oncol., 10, 1 (2021); https://doi.org/10.21037/cco-20-117
  10. B. Escudier, F. Worden and M. Kudo, Sorafenib: Key Lessons from Over 10 Years of Experience, Expert Rev. Anticancer Ther., 19, 177 (2019); https://doi.org/10.1080/14737140.2019.1559058
  11. A. Mazzocca, A. Napolitano, M. Silletta, M. Spalato Ceruso, D. Santini, G. Tonini and B. Vincenzi, New Frontiers in the Medical Management of Gastrointestinal Stromal Tumours, Ther. Adv. Med. Oncol., 11, 1758835919841946 (2019); https://doi.org/10.1177/1758835919841946
  12. D. Strumberg, M.E. Scheulen, B. Schultheis, H. Richly, A. Frost, M. Büchert, O. Christensen, M. Jeffers, R. Heinig, O. Boix and K. Mross, Regorafenib (BAY 73-4506) in Advanced Colorectal Cancer: A Phase I Study, Br. J. Cancer, 106, 1722 (2012); https://doi.org/10.1038/bjc.2012.153
  13. W. Xuan, W. Ding, H.X. Hui and S. Zhang, Synthesis and Cytotoxic Activity of Diaryl Urea Derivatives with a 4-methylpiperazinylcarbonyl Moiety, Med. Chem. Res., 22, 3857 (2013); https://doi.org/10.1007/s00044-012-0398-y
  14. H.J. Kim, H.J. Cho, H. Kim, M.I. El-Gamal, C.-H. Oh, S.H. Lee, T. Sim, J.-M. Hah and K.H. Yoo, New Diarylureas and Diarylamides Possessing Acet(benz)Amidophenyl Scaffold: Design, Synthesis, and Antiproliferative Activity against Melanoma Cell Line, Bioorg. Med. Chem. Lett., 22, 3269 (2012); https://doi.org/10.1016/j.bmcl.2012.03.020
  15. H.B. El-Nassan, Recent Progress in the Identification of BRAF Inhibitors as Anti-cancer Agents, Eur. J. Med. Chem., 72, 170 (2014); https://doi.org/10.1016/j.ejmech.2013.11.018
  16. C. Wang, H. Gao, J. Dong, Y. Zhang, P. Su, Y. Shi and J. Zhang, Biphenyl Derivatives Incorporating Urea Unit as Novel VEGFR-2 Inhibitors: Design, Synthesis and Biological Evaluation, Bioorg. Med. Chem., 22, 277 (2014); https://doi.org/10.1016/j.bmc.2013.11.027
  17. S. Ravez, A. Barczyk, P. Six, A. Cagnon, A. Garofalo, L. Goossens and P. Depreux, Inhibition of Tumor Cell Growth and Angiogenesis by 7-Aminoalkoxy-4-aryloxy-quinazoline ureas, A Novel Series of Multi-Tyrosine Kinase Inhibitors, Eur. J. Med. Chem., 79, 369 (2014); https://doi.org/10.1016/j.ejmech.2014.04.007
  18. S.A. Mitchell, M.D. Danca, P.A. Blomgren, J.W. Darrow, K.S. Currie, J.E. Kropf, S.H. Lee, S.L. Gallion, J.M. Xiong, D.A. Pippin, R.W. DeSimone, D.R. Brittelli, D.C. Eustice, A. Bourret, M. Hill-Drzewi, P.M. Maciejewski and L.L. Elkin, Imidazo[1,2-a]pyrazine Diaryl Ureas: Inhibitors of the Receptor Tyrosine Kinase EphB4, Bioorg. Med. Chem. Lett., 19, 6991 (2009); https://doi.org/10.1016/j.bmcl.2009.10.037
  19. Y.Y. Lu, C.R. Zhao, R.Q. Wang, W.B. Li and X.J. Qu, A Novel Anti-cancer Diarylurea Derivative HL-40 as a Multi-Kinases Inhibitor with Good Pharmacokinetics in Wistar Rats, Biomed. Pharmacother., 69, 255 (2015); https://doi.org/10.1016/j.biopha.2014.11.003
  20. M.L. Curtin, R.R. Frey, H.R. Heyman, N.B. Soni, P.A. Marcotte, L.J. Pease, K.B. Glaser, T.J. Magoc, P. Tapang, D.H. Albert, D.J. Osterling, A.M. Olson, J.J. Bouska, Z. Guan, L.C. Preusser, J.S. Polakowski, K.D. Stewart, C. Tse, S.K. Davidsen and M.R. Michaelides, Thienopyridine Ureas as Dual Inhibitors of the VEGF and Aurora Kinase Families, Bioorg. Med. Chem. Lett., 22, 3208 (2012); https://doi.org/10.1016/j.bmcl.2012.03.035
  21. R. Herowati and G.P. Widodo, Molecular Docking Studies of Chemical Constituents of Tinospora cordifolia on Glycogen Phosphorylase, Procedia Chem., 13, 63 (2014); https://doi.org/10.1016/j.proche.2014.12.007
  22. S.S. Qawoogha and A. Shahiwaka, Identification of Potential Anticancer Phytochemicals against Colorectal Cancer by Structure-based Docking Studies, J. Recept. Signal Transduct. Res., 40, 67 (2020); https://doi.org/10.1080/10799893.2020.1715431
  23. Y. Aoki and Y. Matsubara, Ras/MAPK Syndromes and Childhood Hemato-oncological Diseases, Int. J. Hematol., 97, 30 (2013); https://doi.org/10.1007/s12185-012-1239-y
  24. Y. Wang, H. Nie, X. Zhao, Y. Qin and X. Gong, Bicyclol Induces Cell Cycle Arrest and Autophagy in HepG2 Human Hepatocellular Carcinoma Cells through the PI3K/AKT and Ras/Raf/MEK/ERK Pathways, BMC Cancer, 16, 742 (2016); https://doi.org/10.1186/s12885-016-2767-2
  25. M. Kohler, S. Ehrenfeld, S. Halbach, M. Lauinger, U. Burk, N. Reischmann, S. Cheng, C. Spohr, F.M. Uhl, N. Köhler, K. Ringwald, S. Braun, C. Peters, R. Zeiser, T. Reinheckel and T. Brummer, B-Raf Deficiency Impairs Tumor Initiation and Progression in a Murine Breast Cancer Model, Oncogene, 38, 1324 (2019); https://doi.org/10.1038/s41388-018-0663-8