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

被引：82

作者：

Mohammadi-Khanaposhtani, Maryam ^{[1
,2
]}

Shabani, Mohammad ^{[3
]}

Faizi, Mehrdad ^{[4
]}

Aghaei, Iraj ^{[5
]}

Jahani, Reza ^{[4
]}

Sharafi, Zainab ^{[6
]}

Zafarghandi, Narges Shamsaei ^{[1
,2
]}

Mahdavi, Mohammad ^{[1
,2
]}

Akbarzadeh, Tahmineh ^{[1
,2
,7
]}

Emami, Saeed ^{[8
,9
]}

Shafiee, Abbas ^{[1
,2
]}

Foroumadi, Alireza ^{[1
,2
,10
]}

机构：

[1] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran, Iran

[2] Univ Tehran Med Sci, Pharmaceut Sci Res Ctr, Tehran, Iran

[3] Kerman Univ Med Sci, Neurosci Res Ctr, Inst Neuropharmacol, Kerman, Iran

[4] Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmacol & Toxicol, Tehran, Iran

[5] Guilan Univ Med Sci, Social Determinants Hlth Res Ctr, Rasht, Iran

[6] Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmaceut Biotechnol, Tehran, Iran

[7] Univ Tehran Med Sci, Persian Med & Pharm Res Ctr, Tehran, Iran

[8] Mazandaran Univ Med Sci, Fac Pharm, Dept Med Chem, Sari, Iran

[9] Mazandaran Univ Med Sci, Fac Pharm, Pharmaceut Sci Res Ctr, Sari, Iran

[10] Univ Tehran Med Sci, Drug Design & Dev Res Ctr, Tehran, Iran

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 112卷

基金：

美国国家科学基金会;

关键词：

Anticonvulsant agents; Acridone; Benzodiazepine (BZD) receptors; Docking study; 1,2,4-Oxadiazole; MODELS; ASSAY;

D O I：

10.1016/j.ejmech.2016.01.054

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：91 / 98

页数：8

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