Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents
Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents
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DOI：
10.1016/j.ejmech.2016.01.054
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发表时间：
2016-04-13
影响因子：
6.7
通讯作者：
Foroumadi, Alireza
中科院分区：
文献类型：
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作者：
Mohammadi-Khanaposhtani, Maryam;Shabani, Mohammad;Foroumadi, Alireza
已经合成了许多基于吖啶酮的恶二唑11 a-n，并评价了它们对戊四唑（PTZ）和最大电休克（MES）诱导的小鼠癫痫发作的抗惊厥活性。并通过转棒试验评价其神经毒性。与标准药物苯巴比妥相比，大多数化合物具有更好的抗惊厥活性和更高的安全性。在所测试的衍生物中，化合物111的ED 50值为2.08 mg/kg，是PTZ测试中最有效的化合物。化合物111的抗惊厥作用被氟马西尼阻断，表明苯二氮卓类（BZD）受体参与原型化合物111的抗惊厥活性。此外，化合物111在GABA（A）受体的BZD结合位点中的对接研究证实了化合物111与BZD受体的可能结合。(C)2016 Elsevier Masson SAS。All rights reserved.
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.