Evaluation of neurobiological and antioxidant effects of novel melatonin analogs in mice
| Autor: | Tzveta Stoyanova, Veselina Uzunova, Jana Tchekalarova, Zlatina Nenchovska, Natasha Ivanova, Pavlina Andreeva-Gateva, Rumiana Tzoneva, Violina T. Angelova, Alex Tzonev, Slavina Surcheva |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
Pharmaceutical Science Pharmacology Anxiety Anxiolytic Open field Melatonin 03 medical and health sciences Mice 0302 clinical medicine Desipramine medicine Hot plate test 030304 developmental biology 0303 health sciences Chemistry Depression Melatonin analogs lcsh:RM1-950 Neurotoxicity medicine.disease Tail suspension test lcsh:Therapeutics. Pharmacology Oxidative stress 030220 oncology & carcinogenesis Original Article Analgesia medicine.drug Behavioural despair test |
| Zdroj: | Saudi Pharmaceutical Journal : SPJ Saudi Pharmaceutical Journal, Vol 28, Iss 12, Pp 1566-1579 (2020) |
| ISSN: | 1319-0164 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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