Based on the pharmacophore model of melatonin (MT₁) receptor, we recently synthesized a series of indole derivatives that showed anticonvulsant activity with low neurotoxicity and hepatotoxicity in rodents. In the present study, the three most potent C3-modified derivatives with hydrazine structure 3c, 3e, and 3f, with 2-chlorophenyl, 2-furyl, and 2-thienyl fragments, respectively, were selected, and their neurobiological activity was explored in mice. In Experiment #1, the dose-dependent anxiolytic effect of a single i.p. administration of the novel compounds at doses of 10, 30, and 60 mg/kg were studied in the open field (OF) test. In Experiment#2, the analgesic effect of 3c, 3e, and 3f (30–100 mg/kg) was tested in the hot plate test and formalin test. Experiment#3 was designed to assess the antidepressant-like activity of 3c, 3e, and 3f (10–60 mg/kg). The forced swimming test (FST) and tail suspension test (TST)-induced effect on markers of oxidative stress in the frontal cortex (FC), and the hippocampus was evaluated. Melatonin was used in the same doses as melatonin analogs in all three experiments as a positive control. Desipramine (10 mg/kg) was also applied as a control in the FST. The three melatonin analogs bearing hydrazide/hydrazone substitution at 3C of the indol scaffold demonstrated improved antidepressant-like activity compared to the melatonin. The tested substances are devoided of anxiolytic effects. The antioxidant activity of the melatonin analogs and analgesic potential is comparable to that of melatonin. The 3C substitution with hydrazide/hydrazone moiety substantially contributes to the antidepressant and antioxidant activity of the melatonin analogs.

基于褪黑素（MT ₁）受体的药效团模型，我们最近合成了一系列吲哚衍生物，它们在啮齿动物中显示出抗惊厥活性，并且具有低神经毒性和肝毒性。在本研究中，选择了肼结构3c，3e和3f分别具有2-氯苯基，2-呋喃基和2-噻吩片段的三种最有效的C3修饰衍生物，并探讨了它们的神经生物学活性。老鼠。在实验＃1中，在开阔田野（OF）测试中研究了以10、30和60 mg / kg的剂量单次ip施用新型化合物的剂量依赖性抗焦虑作用。在实验2中，镇痛药的镇痛作用在热板测试和福尔马林测试中测试了3c，3e和3f（30-100 mg / kg）。实验＃3旨在评估3c，3e和3f的抗抑郁样活性（10–60 mg / kg）。评估了强迫游泳试验（FST）和尾部悬吊试验（TST）对额叶皮层（FC）和海马中氧化应激标记物的影响。在所有三个实验中，褪黑激素以与褪黑激素类似物相同的剂量用作阳性对照。地西拉明（10 mg / kg）也用作FST的对照。与褪黑激素相比，在吲哚支架上3℃带有酰肼/ hydr取代的三种褪黑激素类似物表现出改善的抗抑郁样活性。被测物质没有抗焦虑作用。褪黑激素类似物的抗氧化活性和止痛潜力与褪黑激素相当。酰肼/ hydr部分的3C取代基本上有助于褪黑激素类似物的抗抑郁和抗氧化活性。