Anticonvulsant evaluation of 2-pyrazolines carrying naphthyl moiety: An insight into synthesis and molecular docking study

  • Birjees Nusrat Jamia Hamdard, Faculty of Pharmacy
  • Nadeem Siddiqui Jamia Hamdard, Faculty of Pharmacy https://orcid.org/0000-0002-9572-9325
  • Meeta Sahu Jamia Hamdard, Faculty of Pharmacy
  • Mohd. Javed Naim Jamia Hamdard, Faculty of Pharmacy
  • Mohammad ShaharYar Jamia Hamdard, Faculty of Pharmacy
  • Ruhi Ali Jamia Hamdard, Faculty of Pharmacy
  • Ozair Alam Jamia Hamdard, Faculty of Pharmacy
Keywords: Pyrazolines, Anticonvulsants, Molecular docking, Neurotoxicity

Abstract

A series of N-substituted-3-(napthalen-2-yl)-5-substituted phenyl-4,5-dihydropyrazole-1-carbothioamide derivatives (4a-n) were synthesized with the view of structural requirements of pharmacophore for potential anticonvulsant agents. The synthesized compounds were assayed intraperitoneally (i.p.) and subcutaneously (s.c.) in mice against seizures induced by MES and scPTZ methods, respectively. Neurologic deficit was evaluated by rotarod method. Among the tested compounds, 4g, 4i, 4j and 4n emerged as the most active molecule in the MES model at a dose of 30 mg/kg at 0.5h comparable to standardscarbamazepine and phenytoin. In the scPTZ test,4e and 4l were found to be most active compounds at the lowest dose of 30 mg/kg at 0.5h, in the management of the convulsive disorder. Molecular docking studies of the titled compounds were also donewith 3D crystal structure of human cytosolic branched chain amino transferase (hBCATc) enzyme and compound 4e was found to have five hydrogen bond interactions with the most important active site residues.In neurotoxicity studies, except compounds 4b, 4c, 4h and 4k, rest of the compounds showed no sign of toxicity.

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Published
2019-11-29
How to Cite
Nusrat, B., Siddiqui, N., Sahu, M., Naim, M., ShaharYar, M., Ali, R., & Alam, O. (2019). Anticonvulsant evaluation of 2-pyrazolines carrying naphthyl moiety: An insight into synthesis and molecular docking study. Brazilian Journal of Pharmaceutical Sciences, 55, e00249. https://doi.org/10.1590/s2175-97902019000100249
Section
Articles