We synthesized a series of novel indole compounds containing aroylhydrazone moieties and evaluated them in mice to check their anticonvulsant activity. In the present study the most potent C3-modified derivative 3e, containing 2-furyl fragment was evaluated in kainate (KA)-induced status epilepticus (SE) and the consequences on oxidative stress and inflammation in the hippocampus in mice were explored. Melatonin was used as positive control while the melatonin receptor antagonist Luzindol was studied alone or in combination with melatonin or 3e, respectively. After intraperitoneal (i.p.) pre-treatment with melatonin 3e, Luzindol + melatonin and Luzindol + 3e for 7 days (melatonin and 3e—30 mg kg⁻¹ or 60 mg kg⁻¹, Luzindol 10 mg kg⁻¹) the animals were i.p. injected with KA (30 mg kg⁻¹, i.p.). The 3e decreased the SE-induced seizure intensity while melatonin suppressed seizures at the higher dose of 60 mg kg⁻¹. Luzindol blocked the anticonvulsant effect of both Mel and 3e. The dose-dependent antioxidant effect of 3e measured by reduced glutathione (GSH) and total GSH in the hippocampus, was comparable to the effect of melatonin. Luzindol fully blocked the effect of melatonin but affected partially the antioxidant activity of 3e. The KA-induced increased amplifier of neuroinflammation high-mobility group box protein 1 (HMGB1) was neither alleviated by melatonin, nor by 3e. The activation by this DNA-binding protein receptor for advanced glycation end products (RAGE) was not affected by SE, melatonin and 3e pre-treatment. Our results suggest that the novel indole derivate 3e, containing 2-furyl fragment, might be clinically useful as an adjunct therapy against SE and concomitant oxidative stress.

我们合成了一系列含有芳酰腙部分的新型吲哚化合物，并在小鼠身上进行了评估，以检查它们的抗惊厥活性。在本研究中，在红藻氨酸 (KA) 诱导的癫痫持续状态 (SE) 中评估了含有 2-呋喃基片段的最有效的 C3 修饰衍生物3e ，并探讨了对小鼠海马中氧化应激和炎症的影响。褪黑激素用作阳性对照，而褪黑激素受体拮抗剂 Luzindol 分别单独或与褪黑激素或3e联合研究。用褪黑激素3e、Luzindol + 褪黑激素和 Luzindol +  3e腹腔内 (ip) 预处理7 天后（褪黑激素和3e —30 mg kg^-1或60 mg kg ^-1，Luzindol 10 mg kg ^-1 )动物腹腔注射KA(30 mg kg ^-1，ip)。3e降低了 SE 诱导的癫痫发作强度，而褪黑激素在 60 mg kg -1 的较高剂量下抑制了癫痫^发作。Luzindol 阻断了 Mel 和3e 的抗惊厥作用。通过海马中还原型谷胱甘肽 (GSH) 和总 GSH 测量的3e的剂量依赖性抗氧化作用与褪黑激素的作用相当。Luzindol 完全阻断褪黑激素的作用，但部分影响3e的抗氧化活性. KA 诱导的神经炎症高迁移率组盒蛋白 1 (HMGB1) 放大器的增加既没有被褪黑激素缓解，也没有被3e 缓解。这种 DNA 结合蛋白受体对晚期糖基化终产物 (RAGE) 的激活不受 SE、褪黑激素和3e预处理的影响。我们的研究结果表明，含有 2-呋喃基片段的新型吲哚衍生物3e可能在临床上用作针对 SE 和伴随氧化应激的辅助治疗。