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

2016; Elsevier BV; Volume: 112; Linguagem: Inglês

10.1016/j.ejmech.2016.01.054

1768-3254

Maryam Mohammadi‐Khanaposhtani, Mohammad Shabani, Mehrdad Faizi, Iraj Aghaei, Reza Jahani, Zeinab Sharafi, Narges Shamsaei Zafarghandi, Mohammad Mahdavi, Tahmineh Akbarzadeh, Saeed Emami, Abbas Shafiee, Alireza Foroumadi,

Pharmacological Receptor Mechanisms and Effects

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 11l with ED50 value of 2.08 mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 11l was blocked by flumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 11l. Also, docking study of compound 11l in the BZD-binding site of GABAA receptor confirms possible binding of compound 11l with BZD receptors.