Synthesis and Evaluation of Anti-Epileptic Properties of New Phthalimide-4,5-Dihydrothiazole-Amide Derivatives

Abstract

In this work, a novel series of phthalimide-4,5-dihydrothiazole-amide derivatives 5a–f have been synthesized and evaluated for their anti-epileptic activities against pentylenetetrazole (PTZ)-induced seizure in mice. Among the synthesized compounds, the most potent was 4-chloro derivative 5b with zero mortality in PTZ test. Molecular docking was performed to investigate the modes of interactions between GABA_A receptor and synthetized compounds. Docking results were in good agreement with observed experimental data and indicate that among six new derivatives, compound 5b with highest effective anticonvulsant properties, had lowest binding energy. This compound also exhibited better anti-epileptic activity and lower binding energy for connect to GABA_A receptor in comparison to thalidomide as standard anti-epileptic agent.

Keywords:

• Anti-epileptic
• epilepsy
• molecular docking
• phthalimide
• synthesis
• thalidomide

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

Financially supported by Tehran University of Medical Science is gratefully acknowledged.