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Synthesis of new benzimidazole and phenylhydrazinecarbothiomide hybrids and their anticonvulsant activity


A series of new benzimidazole derivatives (4ap) were synthesized and evaluated for anticonvulsant activity in albino mice against two most adopted models, i.e. maximal electroshock seizure (MES)- and subcutaneous pentylenetetrazole (scPTZ)-induced seizures. Synthesized compounds were also screened for possible neurotoxicity using rotarod test. Among the synthesized compounds, 4p showed the most promising activity in MES and scPTZ screens, which was further subjected for oral activity in rats. At a dose of 30 mg/kg, it showed tremendous activity in the scPTZ screen. The acute toxicity study (LD50) of compounds showed that only two tested compounds 4f and 4m did not produce any mortality at any of the dose level. Molecular properties and pharmacokinetic parameters of the titled compounds were also determined using Lipinski’s rule of five. The promising results encourage future investigation on the rational modification of this nucleus for development of better compounds.

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Authors are thankful to National Institute of Neurological Disorders and Stroke (NINDS) for pharmacological work and Dr. Ozair Alam for performing molecular docking study.

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Correspondence to Nadeem Siddiqui.

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Siddiqui, N., Alam, M.S., Ali, R. et al. Synthesis of new benzimidazole and phenylhydrazinecarbothiomide hybrids and their anticonvulsant activity. Med Chem Res 25, 1390–1402 (2016).

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  • Anticonvulsant
  • Glutamate
  • Benzimidazole
  • In silico
  • In vivo
  • Molecular docking