Student Research Committe, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Bioorg Chem. 2018 Aug;78:119-129. doi: 10.1016/j.bioorg.2018.03.001. Epub 2018 Mar 7.
A series of phenacyl triazole hydrazones 3 have been designed based on the hybridization of (arylalkly)triazole and aroyl hydrazone scaffolds as new anticonvulsant agents. The target compounds 3 were easily synthesized from appropriate phenacyl triazoles and aryl acid hydrazides and characterized by IR, NMR and Mass spectroscopy. The in vivo anticonvulsant evaluation of synthesized compounds by using MES and PTZ tests revealed that they are more effective in MES model respect to PTZ test. All compounds showed 33-100% protection against MES-induced seizures at the dose of 100 mg/kg. However, the isonicotinic acid hydrazide derivative 3h showed the best profile of activity in both models. Molecular docking studies of compound 3h with different targets (NMDA, AMPA, GABA and sodium channel), postulated that the compound acts mainly via GABA receptors. In silico molecular properties predictions indicated that all compounds have favourable oral bioavailability and BBB permeability.
基于芳基烷三唑和芳酰腙支架的杂交，设计了一系列苯乙酮三唑腙 3 作为新型抗惊厥药物。目标化合物 3 可通过适当的苯乙酮三唑和芳基酸酰肼轻松合成，并通过 IR、NMR 和质谱进行表征。使用 MES 和 PTZ 试验对合成化合物进行体内抗惊厥评估表明，与 PTZ 试验相比，它们在 MES 模型中更有效。所有化合物在 100mg/kg 剂量下对 MES 诱导的癫痫发作均有 33-100%的保护作用。然而，异烟酰肼衍生物 3h 在两种模型中均表现出最佳的活性特征。化合物 3h 与不同靶点（NMDA、AMPA、GABA 和钠离子通道）的分子对接研究表明，该化合物主要通过 GABA 受体起作用。基于计算的分子特性预测表明，所有化合物均具有良好的口服生物利用度和 BBB 渗透性。
