Micaela Domingues

Universidade Federal de Pelotas

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Lucielli Savegnago

Universidade Federal de Pelotas

Angela Maria Casaril

The University of Texas MD Anderson Cancer Center

Eder J. Lenardão

Universidade Federal de Pelotas

Beatriz Vieira

Centro Universitário de Araraquara

Tiago Collares

Universidade Federal de Pelotas

Fabiana K. Seixas

Universidade Federal de Pelotas

Paloma T. Birmann

Universidade Federal de Pelotas

Darling de Andrade Lourenço

Universidade Federal de Pelotas

Suely Ribeiro Bampi

Universidade Federal de Pelotas

Karine R. Begnini

Hospital de Clínicas de Porto Alegre

Cooperative Institutions

Universidade Federal de Pelotas

University Medical Center of the Johannes Gutenberg University Mainz

Johannes Gutenberg University Mainz

Universidade Federal de Santa Maria

Universidade Federal do Rio Grande do Sul

University of Cologne

University Hospital Cologne

Instituto de Ciências Farmacêuticas

Fundação Oswaldo Cruz

Klinik und Poliklinik für Neurologie

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Antidepressant-like effect of a new selenium-containing compound is accompanied by a reduction of neuroinflammation and oxidative stress in lipopolysaccharide-challenged mice

Journal of Psychopharmacology (2017)

Angela Maria Casaril Micaela Domingues Mariana G. Fronza Beatriz Vieira Karine R. Begnini

Organoselenium compounds and indoles have gained attention due to their wide range of pharmacological properties. Depression is a recurrent and disabling psychiatric illness and current evidences support that oxidative stress and neuroinflammation are mechanisms underlying the pathophysiology of this psychiatric condition. Here, we evaluated the effect of 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI) in lipopolysaccharide (LPS)-induced depressive-like behaviour, neuroinflammation and oxidative stress in male mice. CMI pre-treatment (20 and 50 mg/kg, intragastrically) significantly attenuated LPS (0.83 mg/kg, intraperitoneally)-induced depressive-like behaviour in mice by reducing the immobility time in the tail suspension test (TST) and forced swimming test (FST). CMI pre-treatment ameliorated LPS-induced neuroinflammation by reducing the levels of interleukin (IL)-1β, IL-4 and IL-6 in the hippocampus and prefrontal cortex, as well as markers of oxidative damage. Additionally, we investigated the toxicological effects of CMI (200 mg/kg, i.g.) in the liver, kidney and brain through determination of the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), δ-aminolevulinate dehydratase (δ-ALA-D) and creatinine levels. These biomarkers were not modified, indicating the possible absence of neuro-, hepato- and nephrotoxic effects. Our results suggest that CMI could be a therapeutic approach for the treatment of depression and other neuropsychiatric disorders associated with inflammation and oxidative stress.

Tail suspension test

10.1177/0269881117711713

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Citations (64)

Convenient Michael addition/β-elimination approach to the synthesis of 4-benzyl- and 4-aryl-selenyl coumarins using diselenides as selenium sources

Tetrahedron Letters (2017)

Gustavo Padilha Paloma T. Birmann Micaela Domingues Teodoro S. Kaufman Lucielli Savegnago

Michael reaction

Tandem

10.1016/j.tetlet.2017.01.084

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Ultrasound‐Assisted Synthesis and Antioxidant Activity of 3‐Selanyl‐1 H‐indole and 3‐Selanylimidazo[1,2‐a]pyridine Derivatives

Asian Journal of Organic Chemistry (2017)

Beatriz Vieira Samuel Thurow Monaliza da Costa Angela Maria Casaril Micaela Domingues

Abstract A simple and rapid method for the selective synthesis of 3‐(organylselanyl)‐1 H ‐indoles and 3‐(organylselanyl)imidazo[1,2‐ a ]pyridines catalyzed by CuI/SeO 2 under ultrasound irradiation was developed. This protocol employs a diverse range of 1 H ‐indoles or imidazo[1,2‐ a ]pyridines and diorganyl diselenides to afford the corresponding products selectively in good to excellent yields. Moreover, the antioxidant activity of these compounds was evaluated by using a wide range of in vitro assays, such as 2‐azinobis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical, ferric ion reducing antioxidant power (FRAP), and inhibition of reactive species formation in mice cortex. The bioassays revealed that both classes of the newly synthesized organoselenium compounds present antioxidant activity, with emphasis on the 3‐(organylselanyl)‐1 H ‐indoles. This pharmacological activity opens a wide range of biological applications where the reduction of oxidative stress is essential.

ABTS

10.1002/ajoc.201700339

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Citations (75)

Selanylimidazopyridine abolishes inflammation- and stress-induced depressive-like behaviors by modulating the oxido-nitrosative system

European Journal of Pharmacology (2021)

Micaela Domingues Angela Maria Casaril Thiago Ângelo Smaniotto Paloma T. Birmann Darling de Andrade Lourenço

Tail suspension test

Depression

10.1016/j.ejphar.2021.174570

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Citations (7)

Organocatalysis in the Synthesis of 1,2,3‐Triazoyl‐zidovudine Derivatives: Synthesis and Preliminary Antioxidant Activity

ChemistrySelect (2020)

Carolina B. Gomes Renata A. Balaguez Allya Larroza Thiago Ângelo Smaniotto Micaela Domingues

Abstract We describe herein the organocatalyzed synthesis and preliminary results of antioxidant activities of a range of 1,2,3‐triazoyl‐zidovudine derivatives. These hybrid compounds were synthesized in moderate to excellent yields by reacting zidovudine 1 with a variety of functionalized keto compounds 2 , such as β‐keto‐esters, β‐diketones, β‐keto‐amides, α‐keto‐nitriles, and β‐keto‐sulfones, in the presence of a catalytic amount of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) (10 mol %). Furthermore, the synthesized compounds were screened for their in vitro antioxidant activity. Compounds 3 a , 3 d , 3 g , and 3 l inhibited the formation of reactive oxygen species (ROS) and lipid peroxidation in the prefrontal cortex and hippocampus of mice with similar potency and efficacy.

10.1002/slct.202003355

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The antioxidant and immunomodulatory compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole attenuates depression-like behavior and cognitive impairment developed in a mouse model of breast tumor

Brain Behavior and Immunity (2019)

Angela Maria Casaril Micaela Domingues Suely Ribeiro Bampi Darling de Andrade Lourenço Thiago Ângelo Smaniotto

Neurochemical

10.1016/j.bbi.2019.12.005

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Citations (32)

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

European Journal of Pharmacology (2018)

Paloma T. Birmann Fernanda Severo Sabedra Sousa Daniela Hartwig Micaela Domingues Beatriz Vieira

Ketanserin

Opioidergic

10.1016/j.ejphar.2018.03.005

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Citations (31)

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

Journal of Trace Elements in Medicine and Biology (2019)

Paloma T. Birmann Fernanda Severo Sabedra Sousa Micaela Domingues César Augusto Brüning Beatriz Vieira

Hot plate test

10.1016/j.jtemb.2019.04.014

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Citations (29)

Selanylimidazopyridine Prevents Lipopolysaccharide-Induced Depressive-Like Behavior in Mice by Targeting Neurotrophins and Inflammatory/Oxidative Mediators

Frontiers in Neuroscience (2018)

Micaela Domingues Angela Maria Casaril Paloma T. Birmann Darling de Andrade Lourenço Beatriz Vieira

Inasmuch, as the major depressive disorder (MDD), has been characterized as a heterogeneous disease as the inflammatory processes, neurotrophic factors dysfunction and oxidative/nitrosative stress are believed to a play vital role in its establishment. Organoselenium compounds stand out due to their antioxidant, anti-inflammatory, neuroprotective and antidepressant effects. In this sense, the present study investigated the effect of 3-((4-methoxyphenyl)selanyl)-2-phenylimidazo[1,2-a)pyridine (MPI; 20 and 50 mg/kg, i.g.) pretreatment (30 min prior lipopolysaccharide (LPS) challenge (0.83 mg/kg)) on acute LPS induced depressive-like behavior, neuroinflammation and oxidative stress. MPI was able to prevent the increased immobility time induced by LPS on the forced swimming test (FST), prevented the increase in proinflammatory cytokines expression in the hippocampus of mice after LPS challenge via NFkB down-regulation, and prevented the increase of the reactive oxygen species generation and lipid peroxidation in the prefrontal cortex and hippocampus of mice. It was observed that at the doses tested, MPI protected against reducing levels of BDNF in the cortex and hippocampus of mice challenged with LPS. These observations suggest that the antidepressant-like effect of MPI depends on its capacity to modulate the inflammatory, antioxidant and neurotrophic systems.

Sickness behavior

10.3389/fnins.2018.00486

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Citations (34)

Depression- and anxiogenic-like behaviors induced by lipopolysaccharide in mice are reversed by a selenium-containing indolyl compound: Behavioral, neurochemical and computational insights involving the serotonergic system

Journal of Psychiatric Research (2019)

Angela Maria Casaril Micaela Domingues Darling de Andrade Lourenço Paloma T. Birmann Nathalia B. Padilha

Tail suspension test

Anxiogenic

Neurochemical

10.1016/j.jpsychires.2019.05.006

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Citations (37)