Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents

A number of acridone-based oxadiazoles 11a-n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested derivatives, compounds 111 with ED50 value of 2.08 mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 111 was blocked by fiumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 111. Also, docking study of compound 111 in the BZD-binding site of GABA(A) receptor confirms possible binding of compound 111 with BZD receptors. (C) 2016 Elsevier Masson SAS. All rights reserved.