Abstract

In this work, a novel series of phthalimide-4,5-dihydrothiazole-amide derivatives 5a–f have been synthesized and evaluated for their anti-epileptic activities against pentylenetetrazole (PTZ)-induced seizure in mice. Among the synthesized compounds, the most potent was 4-chloro derivative 5b with zero mortality in PTZ test. Molecular docking was performed to investigate the modes of interactions between GABA_A receptor and synthetized compounds. Docking results were in good agreement with observed experimental data and indicate that among six new derivatives, compound 5b with highest effective anticonvulsant properties, had lowest binding energy. This compound also exhibited better anti-epileptic activity and lower binding energy for connect to GABA_A receptor in comparison to thalidomide as standard anti-epileptic agent.

摘要

在这项工作中，合成了一系列新的邻苯二甲酰亚胺-4,5-二氢噻唑-酰胺衍生物5a-f，并评估了它们对戊四唑 (PTZ) 诱导的小鼠癫痫发作的抗癫痫活性。在合成的化合物中，最有效的是 4-氯衍生物5b，在 PTZ 测试中死亡率为零。进行分子对接以研究 GABA _A受体和合成化合物之间的相互作用模式。对接结果与观察到的实验数据非常吻合，表明在六种新衍生物中，化合物5b具有最高的有效抗惊厥特性，具有最低的结合能。与作为标准抗癫痫剂的沙利度胺相比，该化合物还表现出更好的抗癫痫活性和更低的与 GABA _{A受体连接的结合能。}