Article Sidebar

Download
PDF

Main Article Content

Abstract

Molecular docking is the identification of ligand’s correct binding geometry i.e. pose in the binding site and estimation of its binding affinity for rational design of drug molecule. The current study endeavored the high throughput in silico screening of 56 derivatives of dihydropyridazin-3(2H)-one docked with human cytosolic branched chain amino transferase using PyRx-virtual screening tool. Out of 56 compounds, almost all the test compounds showed very good binding affinity score. Gabapentin was used as standard drug which shows binding affinity of -6.2. On the basis of H-bond interactions, compounds 3, 9, 11, 25, 26, 31, 34, 39, 47, 48, 51, 54, 56 were found to be potent outcome for anticonvulsant activity. Compounds 11, 25, 39, 56 showed excellent H-bond interactions with protein active site, Among which compound 11 showed the outstanding interactions with acceptable bond length 2.34, 2.57, 2.62, 3.03 Å.

Keywords

Molecular docking Dihydropyridazin-3(2H)-one Amino transferase PyRx-virtual Gabapentin.

Article Details

License

Copyright (c) 2021 Asian Journal of Organic & Medicinal Chemistry

Creative Commons License

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

How to Cite
Prasad, S., Lal Khokra, S., & Devgun, M. (2021). Molecular Docking Studies of Dihydropyridazin-3(2H)-one Derivatives as Anticonvulsant Agents. Asian Journal of Organic & Medicinal Chemistry, 6(4), 270–283. https://doi.org/10.14233/ajomc.2021.AJOMC-P349
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. N. Berdigaliyev and M. Aljofan, An Overview of Drug Discovery and Development, Future Med. Chem., 12, 939 (2020); https://doi.org/10.4155/fmc-2019-0307
  2. S. Ekins, J. Mestres and B. Testa, In silico Pharmacology for Drug Discovery: Methods for Virtual Ligand Screening and Profiling, Br. J. Pharmacol., 152, 9 (2007); https://doi.org/10.1038/sj.bjp.0707305
  3. A. Sethi, K. Joshi, K. Sasikala and M. Alvala, Eds. V. Gaitonde, P. Karmakar and A. Trivedi, Molecular Docking in Modern Drug Discovery: Principles and Recent Applications, Drug Discovery and Development - New Advances, IntechOpen (2019); https://doi.org/10.5772/intechopen.85991
  4. X.-Y. Meng, H.-X. Zhang, M. Mezei and M. Cui, Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery, Curr. Comput. Aided-Drug Des., 7, 146 (2011); https://doi.org/10.2174/157340911795677602
  5. L. Ferreira, R. dos Santos, G. Oliva and A. Andricopulo, Molecular Docking and Structure-Based Drug Design Strategies, Molecules, 20, 13384 (2015); https://doi.org/10.3390/molecules200713384
  6. G.-F. Yang and X. Huang, Development of Quantitative Structure-Activity Relationships and Its Application in Rational Drug Design, Curr. Pharm. Des., 12, 4601 (2006); https://doi.org/10.2174/138161206779010431
  7. A. Tripathi and V.A. Bankaitis, Molecular Docking: From Lock and Key to Combination Lock, J. Mol. Med. Clin. Appl., 2, 4 (2018); https://doi.org/10.16966/2575-0305.106
  8. D.-A. Silva, G.R. Bowman, A. Sosa-Peinado and X. Huang, A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein, PLOS Comput. Biol., 7, e1002054 (2011); https://doi.org/10.1371/journal.pcbi.1002054
  9. D.M. Lorber and B.K. Shoichet, Flexible Ligand Docking using Conformational Ensembles, Protein Sci., 7, 938 (1998); https://doi.org/10.1002/pro.5560070411
  10. S. Agarwal and R. Mehrotra, An Overview of Molecular Docking, JSM Chem., 1, 5 (2016).
  11. P.J. Jones, E.C. Merrick, T.W. Batts, N.J. Hargus, Y. Wang, J.P. Stables, E.H. Bertram, M.L. Brown and M.K. Patel, Modulation of Sodium Channel Inactivation Gating by a Novel Lactam: Implications for Seizure Suppression in Chronic Limbic Epilepsy, J. Pharmacol. Exp. Ther., 328, 201 (2009); https://doi.org/10.1124/jpet.108.144709
  12. M. Iman, A. Saadabadi, A. Davood, H. Shafaroodi, A. Nikbakht, A. Ansari and M. Abedin, Docking, Synthesis and Anticonvulsant Activity of N-Substituted Isoindoline-1,3-dione, Iran. J. Pharm. Res., 16, 586 (2017).
  13. C.A. Granbichler, G. Zimmermann, W. Oberaigner, G. Kuchukhidze, J.-P. Ndayisaba, A. Taylor, G. Luef, A.C. Bathke and E. Trinka, Potential Years Lost and Life Expectancy in Adults with Newly Diagnosed Epilepsy, Epilepsia, 58, 1939 (2017); https://doi.org/10.1111/epi.13902
  14. G. Gururaj, P. Satishchandra and S. Amudhan, Epilepsy in India I: Epidemiology and Public Health, Ann. Indian Acad. Neurol., 18, 263 (2015); https://doi.org/10.4103/0972-2327.160093
  15. A.K. Ngugi, C. Bottomley, I. Kleinschmidt, J.W. Sander and C.R. Newton, Estimation of the Burden of Active and Life-Time Epilepsy: A Meta-Analytic Approach, Epilepsia, 51, 883 (2010); https://doi.org/10.1111/j.1528-1167.2009.02481.x
  16. S. Engelborghs, R. D’Hooge and P.P. De Deyn, Pathophysiology of Epilepsy, Acta Neurol. Belg., 100, 201 (2000).
  17. P.A. March, Seizures: Classification, Etiologies, and Pathophysiology, Clin. Tech. Small Anim. Pract., 13, 119 (1998); https://doi.org/10.1016/S1096-2867(98)80033-9
  18. T.V. Kodankandath, D. Theodore and D. Samanta, Generalized Tonic-Clonic Seizure, StatPearls Publishing: Treasure Island (FL) (2021).
  19. A. Singh, Lakshmayya and M. Asif, Analgesic and Anti-Inflammatory Activities of Several 4-Substituted-6-(3¢-nitrophenyl)pyridazin-(2H)-3-one Derivatives, Braz. J. Pharm. Sci., 49, 903 (2013); https://doi.org/10.1590/S1984-82502013000400030
  20. M. Asif and A. Singh, Anticonvulsant Activities of 4-Benzylidene-6-(4-methyl-phenyl)-4,5-dihydropyridazin-(2H)-ones and 4-Benzylidene-6-(4-chloro-phenyl)-4,5-dihydropyridazin-(2H)-ones, Open Pharm. Sci. J., 3, 203 (2016); https://doi.org/10.2174/1874844901603010196
  21. M. Asif, A Mini Review on Biological Activities of Pyridazinone Derivatives as Antiulcer, Antisecretory, Antihistamine and Particularly Against Histamine H3R, Mini Rev. Med. Chem., 14, 1093 (2015); https://doi.org/10.2174/1389557514666141127143133
  22. M. Asif, M. Acharya, Lakshmayya and A. Singh, Rajiv Gandhi Univ. Health Sci. J. Pharm. Sci., 5, 81 (2015); https://doi.org/10.5530/rjps.2015.2.7
  23. M. Asif, Antifeedant, Herbicidal and Molluscicidal Activities of Pyridazinone Compounds, Mini Rev. Org. Chem., 10, 113 (2013); https://doi.org/10.2174/1570193X11310020002
  24. C.M.N. Allerton, M.D. Andrews, J. Blagg, D. Ellis, E. Evrard, M.P. Green, K.K.-C. Liu, G. McMurray, M. Ralph, V. Sanderson, R. Ward and L. Watson, Design and Synthesis of Pyridazinone-Based 5-HT2C Agonists, Bioorg. Med. Chem. Lett., 19, 5791 (2009); https://doi.org/10.1016/j.bmcl.2009.07.136
  25. J. Willis, A. Nelson, F.W. Black, A. Borges, A. An and J. Rice, Barbiturate Anticonvulsants: A Neuropsychological and Quantitative Electroencephalographic Study, J. Child Neurol., 12, 169 (1997); https://doi.org/10.1177/088307389701200303
  26. J. Riss, J. Cloyd, J. Gates and S. Collins, Benzodiazepines in Epilepsy: Pharmacology and Pharmacokinetics, Acta Neurol. Scand., 118, 69 (2008); https://doi.org/10.1111/j.1600-0404.2008.01004.x
  27. J.C. Gomora, A.N. Daud, M. Weiergräber and E. Perez-Reyes, Block of Cloned Human T-Type Calcium Channels by Succinimide Antiepileptic Drugs, Mol. Pharmacol., 60, 1121 (2001); https://doi.org/10.1124/mol.60.5.1121
  28. R. Bansal and S. Thota, Med. Chem. Res., 22, 2539 (2013); https://doi.org/10.1007/s00044-012-0261-1
  29. M. Goto, I. Miyahara, K. Hirotsu, M. Conway, N. Yennawar, M.M. Islam and S.M. Hutson, Structural Determinants for Branched-Chain Aminotransferase Isozyme-Specific Inhibition by the Anticonvulsant Drug Gabapentin, J. Biol. Chem., 280, 37246 (2005); https://doi.org/10.1074/jbc.M506486200