3-(4-Chlorophenylselanyl)-1-methyl-1H-indole promotes recovery of neuropathic pain and depressive-like behavior induced by partial constriction of the sciatic nerve in mice.

3-(4-Chlorophenylselanyl)-1-methyl-1H-indole (CMI) is an organoselenium compound that presents antioxidant activity, antinociceptive, anti-inflammatory and antidepressive-like effect in mice in previous studies conducted by our research group. In this study, we evaluate the anti-allodynic, anti-hyperalgesic and antidepressant-like effects of CMI on partial sciatic nerve ligation (PSNL) in male adult Swiss mice (25-35 g) as well as the involvement of oxidative stress in these effects. Mice underwent PSNL surgery and after 4 weeks they were treated with CMI (10 mg/kg, intragastric route [i.g.]) or vehicle. The treatment with CMI (10 mg/kg, i.g.) reversed the increased the percentage of response to Von-Frey Hair (VFH) stimulation, decreased the latency time to nociceptive response in the hot-plate test, increased immobility time in the forced swimming test (FST) and decreased groomings activity in the splash test, all induced by PSNL. Additionally, CMI also reversed increased the levels of reactive oxygen species (ROS) and lipid peroxidation in cortex and hippocampus and plasmatic levels of corticosterone in mice, induced by PSNL. Results demonstrate that CMI reversed behavioral and biochemical alterations in the dyad pain-depression induced by PSNL and possibly modulation of oxidative system.

Effects of a selanylimidazopyridine on the acute restraint stress-induced depressive- and anxiety-like behaviors and biological changes in mice.

In the last decades, selenium-containing compounds have received increasing attention due to their various biological and pharmacological properties. In the present study, we investigated the effects of 3-[(4-methoxyphenyl) selanyl]-2-phenylimidazo[1,2-a] pyridine (MPI; 1, 10 or 50 mg/kg, i.g.) on the acute restraint stress (ARS)-induced depressive- and anxiety-like behaviors in mice and its underlying mechanism of action. We used the open filed test, forced swimming test, and splash test to evaluate depressive-like behavior, and marble burying and elevated plus maze test to measure anxiety-like behavior. We found that MPI attenuated ARS-induced depressive- and anxiety-like behaviors in all behavioral tests, without having an effect in non-stressed mice. MPI prevented the increased in pro-inflammatory cytokines, indoleamine-2,3-dioxygenase (IDO) and inducible nitric oxide synthase (iNOS) expression in brain structures via canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) down-regulation. Additionally, MPI prevented ARS-induced downregulation of brain-derived neurotrophic factor (BDNF), increased reactive oxygen/nitrogen species generation and lipid peroxidation in prefrontal cortex and hippocampus of mice. In addition, MPI blocked the downregulation of glucocorticoid receptors in the prefrontal cortex and hippocampus and reduced the increased circulating level of corticosterone in stressed mice. These results suggested that MPI showed antidepressant- and anxiolytic-like properties and the effects might be associated with the biological changes in the prefrontal cortex and hippocampus.

3-(4-Chlorophenylselanyl)-1-methyl-1H-indole, a new selenium compound elicits an antinociceptive and anti-inflammatory effect in mice.

Several pathologies, such as pain and inflammation, are modulated by different pathways, making it necessary to develop drugs capable of modulating different pathways. Based on that, we investigated the antinociceptive and anti-inflammatory effect of 3-(4-chlorophenylselanyl)-1-methyl-1H-indole (CMI), as well as the systems involved in these actions. This study evaluated the antinociceptive and anti-inflammatory effects of CMI [0.0001-10 mg/kg administered intragastrically (i.g.)] in the formalin, glutamate, hot plate, ear edema induced by croton oil and paw edema induced by formalin tests. In addition, to investigate the mechanism of action, mice were pre-treated with antagonists of adenosinergic, monoaminergic and opioid systems before administration of CMI. The selenium-containing compound decreased the paw licking and biting time in the formalin and glutamate tests, increased the response latency in hot plate test, without ambulatory changes, evaluated in the open field test. CMI was able to reduce both paw and ear edema induced by formalin and croton oil, respectively. Additionally the antinociceptive effect of CMI (0.01 mg/kg) was blocked when mice were pretreated with the antagonists: SCH23390 [D1-receptor antagonist, 0.05 mg/kg, intraperitoneally (i.p.)], WAY100635 (5-HT1A-receptor antagonist, 0.7 mg/kg, i.p.), ondansetron (5-HT3-receptor antagonist, 0.5 mg/kg, i.p.), ketanserin (5-HT2A/2C-receptor antagonist, 0.3 mg/kg, i.p.), naloxone (non-selective antagonist 1 mg/kg, i.p.), caffeine (non-selective antagonist, 3 mg/kg, i.p.) and prazosin (α1-receptor antagonist, 0.15 mg/kg, i.p). These results demonstrate that the antinociceptive effect of CMI is mediated by monaminergic, opioidergic and adenosinergic modulations and can be a promising molecule capable of modulating different pathways for the treatment of pain and inflammation.

Sonochemistry: An efficient alternative to the synthesis of 3-selanylindoles using CuI as catalyst.

Ultrasonic (US) irradiation was successfully used as an alternative energy source to prepare 3-selanylindoles through the direct selanylation of indoles with diorganyl diselenides using CuI (20 mol%) as catalyst and DMSO as the solvent. By using this US-promoted reaction, eleven 3-organylselanylindoles were prepared selectively and in good yields. A comparative study between the reactions under conventional heating, microwave and ultrasound irradiations was performed, and it was observed advantage in using US over the other heating systems.