Menthone Aryl Acid Hydrazones: A New Class of Anticonvulsants

Jainendra      Jain; Y.      Kumar; Reema      Sinha; Rajeev      Kumar; James      Stables

doi:10.2174/157340611794072689

Abstract

A series of ten compounds (Compounds J1 – J10) of (±) 3-menthone aryl acid hydrazone was synthesized and characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvulsant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also determined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the minimal clonic seizure screen at 6 Hz. Compound J6, 4-Chloro-N-(2-isopropyl-5-methylcyclohexylidene) benzohydrazide was found to be the most active compound with MES ED50 of 16.1 mg/kg and protective index (pI) of greater than 20, indicating that (±) 3-menthone aryl acid hydrazone possesses better and safer anticonvulsant properties than other reported menthone derivatives viz. menthone Schiff bases, menthone semicarbazides and thiosemicarbazides.

Keywords: 3-menthone, aryl acid hydrazone, anticonvulsant, MES, scPTZ, minimal clonic seizure, protective index (pI), thin layer chromatography, Epilepsy, paroxysmal, hyper syn-chronous discharges, neurons, antiepi-leptic drug development (AED), CONH2, carbamides (NHCONH), semicar-bazido groups (NNHCONH), gamma amino butyric acid (GABA), analgesic, sedative-hypnotic, anti-HIV activities, chromic acid method, Physicochemical properties, spectral analyses, neurotoxicity, Veego India Digi-tal Melting point apparatus, Infrared (IR) spectra, Shimadzu FTIR spectrophotometer, Brucker Avance 300MHz spectrometer