Acta Pharm. 56 (2006) 259-272

Synthesis of N⁴-(2,4-dimethylphenyl) semicarbazones as 4-aminobutyrate aminotransferase inhibitors

PERUMAL YOGEESWARI,^* DHARMARAJAN SRIRAM, RATHINASABAPATHY THIRUMURUGAN, LOGANTHA RAMAMOORTHY JEEWANLAL SUNIL JIT, JEGADEESAN VAIGUNDA RAGAVENDRAN, RAMKUMAR KAVYA, KAVYA RAKHRA
and VIVEK SARASWAT

pyogee@bits-pilani.ac.in

Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani-333031, India

Several 2,4-dimethylphenyl substituted semicarbazones were synthesized in three steps involving aryl urea and aryl semicarbazide formations. The structures were confirmed by spectral and elemental analyses. All the compounds were evaluated for anticonvulsant activity by using a series of test models including maximal electroshock seizure, subcutaneous pentylenetetrazole and subcutaneous strychnine seizure threshold tests. The compounds were also evaluated for behavioural impairement and depression activity. In the neurochemical investigation, potent compounds were evaluated for their effects on rat brain gamma-aminobutyric acid (GABA) levels and in vitro gamma-aminobutyrate transaminase (Pseudomonas fluorescens) activity. Preliminary studies suggest these compounds exhibit anticonvulsant activity via a GABA-mediated mechanism.

Keywords: 2,4-dimethylphenyl semicarbazones, anticonvulsants, GABA, GABA-transaminase, maximal electroshock, pentylenetetrazole, strychinine