Design, Synthesis and Pharmacological Evaluation of 1,3,4-Oxadiazole Derivatives: as a Novel Anti-Convulsant Agents

Abstract

Epilepsy is most common neurological disorder with the advancement of lifestyle leading to increase in consumption of anticonvulsant agents. This increased use of anticonvulsant agents for long duration in turn is exhibiting the associated limitations and side effect too. Therefore, there is a need to search for effective and safe anticonvulsant agents for the treatment of epilepsy remains a priority in modern pharmacotherapy. 1,3,4 Oxadiazole is a flexible lead molecule for designing potent biologically active agents. In this present study, a novel series of 1,3,4 Oxadiazole derivatives have been designed, docked, synthesized and evaluated In-vivo anticonvulsant activity by using PTZ induced convulsion in mice. Diazepam was used as reference standard at dose 4mg/kg. In silico studies AMPA receptor used as the target protein (PDB Code: 5ZG1). The in-silico research revealed several binding interactions of designed drugs in order to locate the binding site. The structures of the synthesized derivatives were elucidated by spectral analytical methods such as 1H NMR, 13C NMR, FT-IR, HRMS. In vivo and in silico studies proved that all the synthesized derivatives show the promising anticonvulsant activity, when compared with Diazepam. Anticonvulsant activity of compounds was due to presence of electron withdrawing groups like Br, Cl and electron donating groups like OH at 4th position of aromatic ring attached to 1,3,4 Oxadiazole moiety.