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Synthesis, Anticonvulsant Evaluation and Molecular Docking Studies of Novel Benzo[1,3]dioxol-5-yloxy-N′-(4-substituted benzylidene)acetohydrazide Derivatives
Corresponding Author(s) : Laxmi Tripathi
Asian Journal of Chemistry,
Vol. 32 No. 1 (2020): Vol 32 Issue 1
Abstract
Novel (benzo[1,3]dioxol-5-yloxy)-N′-(4-substituted benzylidene)acetohydrazide derivatives were synthesized and their anticonvulsant activity evaluated by MES and scMET seizure models. Compound 2-(benzo[d][1,3]dioxol-5-yloxy)-N′-benzylideneacetohydrazide (4a) was found to be most potent in MES seizure test and showed no neurotoxicity at the highest administered dose. All the compounds showed high docking score with γ-aminobutyric acid receptor, GABAAR-β3 homopentamer (PDB ID: 4COF). Thus, the probable mechanism of action of benzo[1,3]dioxol-5-yloxy-N′-(4-substituted benzylidene)acetohydrazide derivatives (4a-h) may be augmentation of GABAergic activity.
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- L. Tripathi, R. Singh and J. Stables, Eur. J. Med. Chem., 46, 509 (2011); https://doi.org/10.1016/j.ejmech.2010.11.030
- H. Kaur, B. Kumar and M. Bikash, eNeurological Sci., 4, 42 (2016); https://doi.org/10.1016/j.ensci.2016.06.003.
- P. Emilio, F. Jacqueline and B. Meir, Lancet, 6, 793 (2007); https://doi.org/10.1016/S1474-4422(07)70215-6.
- A.J. Cole and S. Wiebe, Epilepsia, 49, s29 (2008); https://doi.org/10.1111/j.1528-1167.2008.01924.x.
- P. Perucca and F.G. Gilliam, Lancet Neurol., 11, 792 (2012); https://doi.org/10.1016/S1474-4422(12)70153-9.
- R. Bairam, S.M. Murthy, A.B. Shaik and S. Kumar, Int. J. Pharm. Sci. Res., 8, 2477 (2017).
- M.P. Canevini, G.D. Sarro, C.A. Galimberti, G. Gatti, L. Licchetta, A. Malerba, G. Muscas, A.L. Neve, P. Striano and E. Perucca, Epilepsia, 51, 797 (2010); https://doi.org/10.1111/j.1528-1167.2010.02520.x.
- V. Angelova, V. Karabeliov and P.A. J. Andreeva-Gateva, Drug Dev. Res., 77, 379 (2016); https://doi.org/10.1002/ddr.21329.
- N. Kumar, L.S. Chauhan, N. Dashora and C.S. Sharma, Schol. Acad. J. Pharm., 3, 366 (2014).
- P. Hassanzadeh, E. Arbabi and F. Rostami, Iran. J. Basic Med Sci., 17, 100 (2014).
- A. Shah, R. Lobo, N. Krishnadas and R. Surubhotla, Indian J. Pharm. Educ. Res., 53, s28 (2019); https://doi.org/10.5530/ijper.53.2s.46.
- P. Kumar, B. Shrivastava, S.N. Pandeya, L. Tripathi and J.P. Stables, Med. Chem. Res., 21, 2428 (2012); https://doi.org/10.1007/s00044-011-9768-0.
- P. Kumar, B. Shrivastava and S.N. Pandeya, Asian J. Chem., 22, 7771 (2010).
- M.M. Castel-Branco, G.L. Alves, I.V. Figueiredo, A.C. Falcão and M.M. Caramona, Methods Find. Exp. Clin. Pharmacol., 31, 101 (2009); https://doi.org/10.1358/mf.2009.31.2.1338414.
- H.S. White, M. Johnson, H.H. Wolf and H.J. Ital, J. Neurol Sci., 16, 73 (1995); https://doi.org/10.1007/BF02229077.
- C.M. Virginia, Toxicol. Pathol., 39, 36 (2011); https://doi.org/10.1177/0192623310385255.
References
L. Tripathi, R. Singh and J. Stables, Eur. J. Med. Chem., 46, 509 (2011); https://doi.org/10.1016/j.ejmech.2010.11.030
H. Kaur, B. Kumar and M. Bikash, eNeurological Sci., 4, 42 (2016); https://doi.org/10.1016/j.ensci.2016.06.003.
P. Emilio, F. Jacqueline and B. Meir, Lancet, 6, 793 (2007); https://doi.org/10.1016/S1474-4422(07)70215-6.
A.J. Cole and S. Wiebe, Epilepsia, 49, s29 (2008); https://doi.org/10.1111/j.1528-1167.2008.01924.x.
P. Perucca and F.G. Gilliam, Lancet Neurol., 11, 792 (2012); https://doi.org/10.1016/S1474-4422(12)70153-9.
R. Bairam, S.M. Murthy, A.B. Shaik and S. Kumar, Int. J. Pharm. Sci. Res., 8, 2477 (2017).
M.P. Canevini, G.D. Sarro, C.A. Galimberti, G. Gatti, L. Licchetta, A. Malerba, G. Muscas, A.L. Neve, P. Striano and E. Perucca, Epilepsia, 51, 797 (2010); https://doi.org/10.1111/j.1528-1167.2010.02520.x.
V. Angelova, V. Karabeliov and P.A. J. Andreeva-Gateva, Drug Dev. Res., 77, 379 (2016); https://doi.org/10.1002/ddr.21329.
N. Kumar, L.S. Chauhan, N. Dashora and C.S. Sharma, Schol. Acad. J. Pharm., 3, 366 (2014).
P. Hassanzadeh, E. Arbabi and F. Rostami, Iran. J. Basic Med Sci., 17, 100 (2014).
A. Shah, R. Lobo, N. Krishnadas and R. Surubhotla, Indian J. Pharm. Educ. Res., 53, s28 (2019); https://doi.org/10.5530/ijper.53.2s.46.
P. Kumar, B. Shrivastava, S.N. Pandeya, L. Tripathi and J.P. Stables, Med. Chem. Res., 21, 2428 (2012); https://doi.org/10.1007/s00044-011-9768-0.
P. Kumar, B. Shrivastava and S.N. Pandeya, Asian J. Chem., 22, 7771 (2010).
M.M. Castel-Branco, G.L. Alves, I.V. Figueiredo, A.C. Falcão and M.M. Caramona, Methods Find. Exp. Clin. Pharmacol., 31, 101 (2009); https://doi.org/10.1358/mf.2009.31.2.1338414.
H.S. White, M. Johnson, H.H. Wolf and H.J. Ital, J. Neurol Sci., 16, 73 (1995); https://doi.org/10.1007/BF02229077.
C.M. Virginia, Toxicol. Pathol., 39, 36 (2011); https://doi.org/10.1177/0192623310385255.