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Vol. 35 No. 11 (2023): Vol 35 Issue 11, 2023

Copyright (c) 2023 GAUTAM BHARDWAJ, SURESH KUMAR, RAJIV KUMAR TONK

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Anticancer and Antimicrobial Screening of Novel Pyrazolo[2,3-c]pyridopyridazine Analogues: Synthesis, Spectral Characterization, Molecular Docking and Dynamics Studies

https://doi.org/10.14233/ajchem.2023.30477
GAUTAM BHARDWAJ
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, Sector-3, New Delhi-110017, India
https://orcid.org/0000-0001-5372-1731
SURESH KUMAR
Division of Medical Laboratory Technology, School of Allied Health Science, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, Sector-3, New Delhi-110017, India
https://orcid.org/0000-0003-0260-0459
RAJIV KUMAR TONK
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, Sector-3, New Delhi-110017, India
https://orcid.org/0000-0002-0842-5121

Corresponding Author(s) : RAJIV KUMAR TONK

tonkrk@dpsru.edu.in

Asian Journal of Chemistry, Vol. 35 No. 11 (2023): Vol 35 Issue 11, 2023

Abstract

A major threat in cancer management is the development of drug resistance and gene mutations. Serine threonine kinases like DYRK1A pathway are potential targets for cancer therapies. In this work, a new series of seven pyrazolo[2,3-c]pyridopyridazine analogs were synthesized and characterized by spectroscopic methods. Three compounds were evaluated for in-vitro anticancer activity following 60 cell lines protocol of NCI, USA and for antimicrobial activity against Gram-negative and Gram-positive bacteria. All the compounds exhibited moderate to good antibacterial activity, while compounds 4a, 4b and 4d showed moderate responses against leukemia, ovarian cancer, and prostate cancer cell lines in anti-proliferative studies.

Keywords

Pyrazolo[2,3-c]pyridopyridazine DYRK1A inhibitors Anticancer activity Computational design
BHARDWAJ, G., KUMAR, S., & TONK, R. K. (2023). Anticancer and Antimicrobial Screening of Novel Pyrazolo[2,3-c]pyridopyridazine Analogues: Synthesis, Spectral Characterization, Molecular Docking and Dynamics Studies. Asian Journal of Chemistry, 35(11), 2837–2844. https://doi.org/10.14233/ajchem.2023.30477
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References
  1. K.D. Seely, A.D. Morgan, L.D. Hagenstein, G.M. Florey and J.M. Small, Cancers, 14, 1019 (2022); https://doi.org/10.3390/cancers14041019
  2. L. Litovchick, L.A. Florens, S.K. Swanson, M.P. Washburn and J.A. DeCaprio, Genes Dev., 25, 801 (2011); https://doi.org/10.1101/gad.2034211
  3. A. Kamb, S. Wee and C. Lengauer, Nat. Rev. Drug Discov., 6, 115 (2007); https://doi.org/10.1038/nrd2155
  4. P. Fernández-Martínez, C. Zahonero and P. Sánchez-Gómez, Mol. Cell. Oncol., 2, e970048 (2015); https://doi.org/10.4161/23723548.2014.970048
  5. A.R.I. Altaba, Sci. Signal., 4, 9 (2011); https://doi.org/10.1126/scisignal.200254
  6. J. Mao, P. Maye, P. Kogerman, F.J. Tejedor, R. Toftgard, W. Xie, G. Wu and D. Wu, J. Biol. Chem., 277, 35156 (2002); https://doi.org/10.1074/jbc.M206743200
  7. C.C. Wu and S.B. Bratton, Mol. Cell. Oncol., 4, e1281865 (2017); https://doi.org/10.1080/23723556.2017.1281865
  8. A. Laguna, S. Aranda, M.J. Barallobre, R. Barhoum, E. Fernández, V. Fotaki, J.M. Delabar, S. de la Luna, P. de la Villa and M.L. Arbonés, Dev. Cell, 15, 841 (2008); https://doi.org/10.1016/j.devcel.2008.10.014
  9. X. Guo, J.G. Williams, T.T. Schug and X. Li, J. Biol. Chem., 285, 13223 (2010); https://doi.org/10.1074/jbc.M110.102574
  10. A. Ionescu, F. Dufrasne, M. Gelbcke, I. Jabin, R. Kiss and D. Lamoral-Theys, Mini-Rev. Med. Chem., 12, 1315 (2012); https://doi.org/10.2174/13895575112091315
  11. N. Pozo, C. Zahonero, P. Fernández, J.M. Liñares, A. Ayuso, M. Hagiwara, A. Pérez, J.R. Ricoy, A. Hernández-Laín, J.M. Sepúlveda and P. Sánchez-Gómez, J. Clin. Invest., 123, 2475 (2013); https://doi.org/10.1172/JCI63623
  12. D.B. Jarhad, K.K. Mashelkar, H.R. Kim, M. Noh and L.S. Jeong, J. Med. Chem., 61, 9791 (2018); https://doi.org/10.1021/acs.jmedchem.8b00185
  13. M.A. Ibrahim, A.H. Elmenoufy, M. Elagawany, M.M. Ghoneim and A. Moawad, J. Biosci. Med., 3, 59 (2015); https://doi.org/10.4236/jbm.2015.310008
  14. R.K. Tonk, S. Bawa, G. Chawla, G.S. Deora, S. Kumar, V. Rathore, N. Mulakayala, A. Rajaram, A.M. Kalle and O. Afzal Eur. J. Med. Chem., 57, 176 (2012); https://doi.org/10.1016/j.ejmech.2012.08.045
  15. A. Daina, O. Michielin and V. Zoete, Sci. Rep., 7, 42717 (2017); https://doi.org/10.1038/srep42717
  16. G.M. Morris, H. Ruth, W. Lindstrom, M.F. Sanner, R.K. Belew, D.S. Goodsell and A.J. Olson, J. Comput. Chem., 30, 2785 (2009); https://doi.org/10.1002/jcc.21256
  17. G.M. Morris, D.S. Goodsell, R.S. Halliday, R. Huey, W.E. Hart, R.K. Belew and A.J. Olson, J. Comput. Chem., 19, 1639 (1998); https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B
  18. BIOVIA, Dassault Systèmes BIOVIA, Discovery Studio Modeling Environment, Release 2017, Dassault Systèmes (2017).
  19. H. Tazarki, W. Zeinyeh, Y.J. Esvan, S. Knapp, D. Chatterjee, M. Schröder, A.C. Joerger, J. Khiari, B. Josselin, B. Baratte, S. Bach, S. Ruchaud, F. Anizon, F. Giraud and P. Moreau, Eur. J. Med. Chem., 166, 304 (2019); https://doi.org/10.1016/j.ejmech.2019.01.052
  20. S. Zhu, J. Chem. Inf. Model., 59, 4239 (2019); https://doi.org/10.1021/acs.jcim.9b00552
  21. P.A. Kollman, I. Massova, C. Reyes, B. Kuhn, S. Huo, L. Chong, M. Lee, T. Lee, Y. Duan, W. Wang, O. Donini, P. Cieplak, J. Srinivasan, D.A. Case and T.E. Cheatham, Acc. Chem. Res., 33, 889 (2000); https://doi.org/10.1021/ar000033j
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