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Abstract: Neurodegenerative and mental disorders are a public health burden with pharma-cological treatments of limited efficacy. Organoselenium compounds are receiving great at-tention in medicinal chemistry mainly because of their antioxidant and immunomodulatory activities, with a multi-target profile that can favor the treatment of multifactorial diseases. Therefore, the purpose of this review is to discuss recent preclinical studies about orga-noselenium compounds as therapeutic agents for the management of mental (e.g., depres-sion, anxiety, bipolar disorder, and schizophrenia) and neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclero-sis). We have summarized around 70 peer-reviewed articles from 2016 to the present that used in silico, in vitro, and/or in vivo approaches to assess the neuropharmacology of seleni-um-containing compounds. Among the diversity of organoselenium molecules investigated in the last five years, diaryl diselenides, Ebselen-derivatives, and Se-containing heterocycles are the most representative. Ultimately, this review is expected to provide disease-oriented information regarding the neuropharmacology of organoselenium compounds that can be useful for the design, synthesis, and pharmacological characterization of novel bioactive molecules that can potentially be clinically viable candidates.

Background: We report the synthesis and antioxidant evaluation of 1-organoselanyl-naphthalen-2-ols. The title compounds were selectively prepared through the selenofunctionalization of 2-naphthol derivatives using benzeneseleninic acids as a selenium source. Objective: We aimed at synthesizing 1-organoselanyl-naphthalen-2-ol by functionalizing 2-naphthol with arylseleninic acids using glycerol as the solvent and further evaluating the pharmacological activity. Methods: The products were synthesized at 70 °C using glycerol as a solvent in an oil bath. Reactive species (RS) tests, DPPH radical scavenging activity assay, and ABTS+ radical scavenging activity assay were performed. A statistical analysis of the data was performed. Results and Discussion: A total of fifteen 1-organoselanyl-naphthalen-2-ols were selectively obtained in yields of 58-95% in 0.25-48 h of reaction. Additionally, all the synthesized seleno-derivatives exhibited antioxidant activity, as revealed by their ability to scavenge DPPH and ABTS+ radicals and reduce the reactive species (RS) levels. Conclusion: The synthesis of 1-arylselanyl-naphthalen-2-ols was developed under mild reaction conditions using benzeneseleninic acid derivatives in reactions with 2-naphthol. All synthesized 2-naphthol derivatives exhibited antioxidant activity, as revealed by their DPPH and ABTS+ radical scavenging activity and reduced RS levels.

A total of thirty-four 3-selanylimidazopyridines were easily prepared in 50–94% yields using bench stable arylseleninic acids as a selenium source.

For many years since its discovery, Selenium has played the role of a bad boy who became a hero in organic transformations. Selenium dioxide, for instance, is one of the most remembered reagents in allylic oxida-tions, having been applied in the synthesis of several naturally occurring products. The main goal of this review is to show the recent advances in the use of classical and new selenium reagents in organic synthesis. As demon-strated through the around 60 references discussed here, selenium can go even forward as a versatile reagent. We bring a collection of selenium reagents and their transformations that still asleep in the eyes of most synthetic or-ganic chemists.

Herein we present an alternative and transition-metal-free procedure to access 3-organoselanylthiochromones and 3-organoselanylchromones from the cyclization reaction between alkynyl aryl ketones and diorganyl diselenides promoted by Oxone®.

The H-shaped [I10Cl4]4− polyhalide is the result of the interplay of directional HBs, XBs and π–π interactions driven by the structural features of the 2-(p-tolyl)selenopheno[2,3-b]pyridinium cation template.

In this paper, a simple and clean process for the alkylation and arylation of nitrogen-containing heterocycles is reported. The reactions were conducted using the Q-tube® as a non-conventional technology, in water as a green solvent, at overboiling temperature. The developed strategy was used to improve two steps in the total synthesis of caffeine, as reported by Narayan, and then extended to the preparation of N-decorated xanthines. Finally, piperidine, methyl piperazine, and isatine were proven to be suitable substrates for the protocol proposed herein.

A new method was developed for the synthesis of 4-chalcogenyl-1H-isochromen-1-ones through the 6-endo-dig electrophilic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides under ultrasound irradiation. The reactions were performed under mild conditions, using Oxone as a green oxidant to promote the cleavage of the chalcogen-chalcogen bond in diorganyl diselenides and ditellurides to generate electrophilic species in situ. A total of 25 compounds were selectively obtained after 30-70 min, in good to excellent yields (74-95%). This procedure was extended to prepare 5H-selenopheno[3,2-c]isochromen-5-ones. Additionally, for the first time, the 4-chalcogenyl-1H-isochromen-1-ones were used as substrates in the thionation reaction, using Lawesson's reagent and microwave irradiation under solvent-free conditions, obtaining the thio derivatives in yields of up to 99% in only 15 min.

We describe herein an alternative and transition-metal-free procedure for the access of benzo[b]chalcogenophenes fused to selenophenes via intramolecular cyclization of 1,3-diynes. This efficient protocol involves a double cyclization of 1,3-diynyl chalcogen derivatives promoted by the electrophilic species of organoselenium generated in situ by the oxidative cleavage of the Se-Se bond of dibutyl diselenide using Oxone® in acetonitrile as solvent in an open-flask at 80 °C. In this study, 15 selenophenes with broad substrate scope were prepared in moderate to excellent yields (55-98%) with short reaction times (0.5-3.0 h).

We report a protocol for the synthesis of 3-organyl-4-(organylchalcogenyl)isoquinoline-2-oxides via electrophilic cyclization between alkynylbenzaldoximes and diorganyl dichalcogenides promoted by ...

Major depressive disorder (MDD) is a chronic mental illness affecting a wide range of people worldwide. The pathophysiology of MDD is not completely elucidated, but it is believed that oxidative stress and neuroinflammation are involved. In light with this, the aim of the present study was to investigate whether a single administration of the antioxidant 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI) was able to reverse the streptozotocin-induced depression-like behavior, oxidative stress, and neuroinflammation in mice. MFSeI (10 mg/kg) was administered intragastrically (i.g.) 24 h after the intracerebroventricular injection of STZ (0.2 mg/4 μL/per mouse). Thirty minutes after MFSeI administration, behavioral tests and neurochemical analyses were performed. Fluoxetine (10 mg/kg, i.g.) was used as a positive control. MFSeI and fluoxetine were able to reverse the STZ-induced depression-like behavior, as evidenced by decreased immobility time in the forced swimming test and increased grooming time in the splash test. Mechanistically, MFSeI reversed the increased levels of reactive species and lipid peroxidation in the prefrontal cortices and hippocampi of STZ-treated mice. Additionally, neuroinflammation (i.e. expression of NF-κB, IL-1β, and TNF-α) and the reduced mRNA levels of BDNF in the and hippocampi of depressed mice were reversed by treatment with MFSeI. Fluoxetine did not improve the STZ-induced alterations at the levels of reactive species, NF-κB and BDNF in the prefrontal cortices neither the levels of TNF-α in both brain regions. Together, these data suggest that the MFSeI may be a promising compound with antidepressant-like action, reducing oxidative stress and modulating inflammatory pathways in the brain of depressed mice.

We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.

This review describes the recent advances in photocatalyzed reactions to form new carbon–sulfur and carbon–selenium bonds. With a total of 136 references, of which 81 articles are presented, the authors introduce in five sections an updated picture of the state of the art in the light-promoted synthesis of organochalcogen compounds (from 2019 to present). The light-promoted synthesis of sulfides by direct sulfenylation of C–C π-bonds; synthesis of sulfones; the activation of Csp2–N bond in the formation of Csp2–S bonds; synthesis of thiol ester, thioether and thioacetal; and the synthesis of organoselenium compounds are discussed, with detailed reaction conditions and selected examples for each protocol.

A metal- and catalyst-free photo-promoted cyclization of properly substituted vinyl selenides was developed using UVA irradiation. A total of eighteen new C3-unsubstituted 2-selanyl benzochalcogenophenes (benzofurans, benzothiophenes and benzoselenophenes) were prepared in 30-86% yield after irradiation with UVA at room temperature. The usefulness of the title compounds was demonstrated in the easy functionalization of the remaining free C-H bond of the benzochalcogenophenes to form new C-Se and C-Br bonds by simple procedures. Furthermore, the reaction can be performed under natural sunlight irradiation and the solvent is easily reused further in several subsequent runs.

Background: This study presents the synthesis and multi-target behavior of the new 5'-hydroxy-3-(chalcogenyl-triazoyl)-thymidine and the biological evaluation of these compounds as antioxidant and anti-HIV agents. Objective: Antiretroviral therapy induces oxidative stress. Based on this, the main objective of this manuscript is the preparation of compounds that combine anti-HIV and antioxidant activities. Methods: The compounds were prepared from commercially available AZT, through a copper-catalyzed Huisgen 1,3-dipolar cycloadditions exploiting the AZT azide group and chalcogenyl alkynes. Results: The chalcogenium-AZT derivatives were obtained in good yields via click chemistry. The compounds evaluated showed antioxidant and anti-HIV activity. Additionally, in vivo toxicity of this class of compounds was also evaluated and the representative nucleoside did not change the survival, behavior, biochemical hepatic, and renal markers compared to the control mice. Conclusion: Data suggest the feasibility of modifying the AZT nucleus with simple organochalcogen fragments, exploring the reactivity of the azide group via 1,3-dipolar Huisgen cycloaddition reaction. The design of these new compounds showed the initially desired biological activities.

We describe here our results from the copper-catalyzed three component reaction of 2-azidobenzaldehyde, anthranilamide and terminal alkynes, using Et3N as base, and DMSO as solvent. Depending on the temperature and amount of Et3N used in the reactions, 1,2,3-triazolyl-quinazolinones or 1,2,3-triazolyl-dihydroquinazolinone could be obtained. When the reactions were performed at 100 °C using 2 equivalents of Et3N, 1,2,3-triazolyl-dihydroquinazolinone was formed in 82% yield, whereas reactions carried out at 120 °C using 1 equivalent of Et3N provided 1,2,3-triazolyl-quinazolinones in moderate-to-good yields.

Oxidative stress and neuroinflammation are found both in diabetes mellitus and major depressive disorder (MDD). In addition to damage in peripheral organs, such as liver and kidney, diabetic patients have a higher risk of developing depression. In this sense, the objective of the present study was to characterize the antidepressant-like effect of a selenium-containing compound, the 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI), in streptozotocin (STZ)-induced diabetic mice. STZ (200 mg/kg, i.p.) was used to induce diabetes mellitus type I, and after seven days, the administration of MFSeI (10 mg/kg, i.g.) was initiated and followed for the next 14 days. Twenty-four hours after the last administration of MFSeI, the behavioral tests were performed, followed by euthanasia. The treatment with MFSeI was able to reverse the hyperglycemia induced by STZ. MFSeI also decreased the plasma levels of biomarkers of liver and kidney damage. Importantly, MFSeI reversed the depression-like behavior induced by STZ in the tail suspension test and forced swimming test without promoting locomotor alterations. Furthermore, MFSeI reversed the increased levels of reactive species and lipid peroxidation in the prefrontal cortex (PFC), hippocampus (HC), liver, and kidney of STZ-treated mice. Treatment with MFSeI also decreased the expression of tumor necrosis factor-alpha, inducible nitric oxide synthase and indoleamine 2,3-dioxygenase, while increasing the expression of interleukin-10, insulin receptor substrate-1 and glucose transport-4 in the PFC and HC of mice. Taken together, the results indicate the effectiveness of MFSeI against depression-like behavior and central and peripheral complications caused by diabetes in mice.