-(4-(1H-1,2,4-三唑-1-基)苯基)取代酰胺衍生物的设计、合成及药理活性

Design, Synthesis, and Pharmacological Activity of the -(4-(1H-1,2,4-Triazol-1-yl)phenyl)-substituted-amide Derivatives.

作者信息

Hu Lina, Li Mengjiao, Liu Zheng, Yan Hui, Wang Xuekun, Wang Shiben

机构信息

State Key Laboratory of Macromolecular Drugs and Large-Scale Preparation, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China.

School of Medicine, Foshan University, Foshan 528000, China.

出版信息

Molecules. 2025 Aug 18;30(16):3400. doi: 10.3390/molecules30163400.

To discover novel, potent anticonvulsant compounds, a series of compounds containing triazole structural fragments were synthesized and evaluated for their anticonvulsant activity. Compounds (maximal electroshock (MES), 50% effective dose (ED) = 13.1 mg/kg; subcutaneous pentylenetetrazole (scPTZ), ED = 19.7 mg/kg) and (MES, ED = 9.1 mg/kg; PTZ, ED = 19.0 mg/kg) showed the best activity in MES and PTZ tests. The results of an affinity test showed that the potent compounds had better binding to the GABA receptors. The results of an inhibitory neurotransmitter GABA content test in brain tissue indicated that compounds and exerted anticonvulsant activity which may be associated with the increase of GABA content in the rat brain. Elevated plus maze (EPM) assay results showed that compounds and possessed anxiolytic effects, and their effects correlated with the binding sites of benzodiazepines (BZs) in the GABA receptors. Molecular docking was performed to investigate the interactions of the studied compound with the GABA receptors on the molecular level.

为了发现新型强效抗惊厥化合物，合成了一系列含有三唑结构片段的化合物，并对其抗惊厥活性进行了评估。化合物（最大电休克（MES），50%有效剂量（ED）=13.1mg/kg；皮下注射戊四氮（scPTZ），ED=19.7mg/kg）和（MES，ED=9.1mg/kg；PTZ，ED=19.0mg/kg）在MES和PTZ试验中表现出最佳活性。亲和力测试结果表明，强效化合物与GABA受体的结合更好。脑组织中抑制性神经递质GABA含量测试结果表明，化合物和发挥抗惊厥活性可能与大鼠脑中GABA含量增加有关。高架十字迷宫（EPM）试验结果表明，化合物和具有抗焦虑作用，其作用与GABA受体中苯二氮䓬（BZ）的结合位点相关。进行分子对接以在分子水平上研究所研究的化合物与GABA受体的相互作用。