50 Years of Organoselenium Chemistry, Biochemistry and Reactivity: Mechanistic Understanding, Successful and Controversial Stories.

In 1973, two major discoveries changed the face of selenium chemistry: the identification of the first mammal selenoenzyme, glutathione peroxidase 1, and the discovery of the synthetic utility of the so-called selenoxide elimination. While the chemical mechanism behind the catalytic activity of glutathione peroxidases appears to be mostly unveiled, little is known about the mechanisms of other selenoproteins and, for some of them, even the function lies in the dark. In chemistry, the capacity of organoselenides of catalyzing hydrogen peroxide activation for the practical manipulation of organic functional groups has been largely explored, and some mechanistic details have been clearly elucidated.

Comparative study of the antiproliferative activity of heterometallic carbene gold(i)-platinum(ii) and gold(i)-palladium(ii) complexes in cancer cell lines.

The stepwise, one-pot synthesis of heterobimetallic carbene gold(i) platinum(ii) complexes from readily available starting materials is presented. The protecting group free methodology is based on the graduated nucleophilicities of aliphatic and aromatic amines as linkers between both metal centers. This enables the selective, sequential installation of the metal fragments.

Reactivity of Zinc Fingers in Oxidizing Environments: Insight from Molecular Models Through Activation Strain Analysis.

The reactivity of Zn tetrahedral complexes with HO was investigated in silico, as a first step in their disruption process. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i. e.

Unveiling the promising anticancer activity of palladium(II)-aryl complexes bearing diphosphine ligands: a structure-activity relationship analysis.

In continuation of our previous works on the cytotoxic properties of organopalladium compounds, in this contribution we describe the first systematic study of the anticancer activity of Pd(II)-aryl complexes. To this end, we have prepared and thoroughly characterized a wide range of palladium derivatives bearing different diphosphine, aryl and halide ligands, developing, when necessary, specific synthetic protocols. Most of the synthesized compounds showed remarkable cytotoxicity towards ovarian and breast cancer cell lines, with IC values often comparable to or lower than that of cisplatin.

Interplay between diphenyl diselenide and copper: Impact on D. melanogaster survival, behavior, and biochemical parameters.

Copper (Cu) is a biologically essential element that participates in numerous physiological processes. However, elevated concentrations of copper have been associated with cellular oxidative stress and neurodegenerative diseases. Organo‑selenium compounds such as diphenyl diselenide (DPDS) have in vitro and in vivo antioxidant properties.

Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2.

The main protease (M) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and activity.

In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans.

Background: The new coronavirus (SARS-CoV-2) pandemic emerged in 2019 causing millions of deaths. Vaccines were quickly developed and made available in 2021. Despite the availability of vaccines, some subjects refuse to take the immunizing or present comorbities, therefore developing serious cases of COVID-19, which makes necessary the development of antiviral drugs.

1,2,3-Triazolo[4,5-b]aminoquinolines: Design, synthesis, structure, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, and molecular docking of novel modified tacrines.

An efficient [4 + 2] cyclization protocol to synthesize a series of twelve examples of 1,2,3-triazolo[4,5-b]aminoquinolines (5) as novel structurally modified tacrines was obtained by reacting readily accessible precursors (i.e., 3-alky(aryl)-5-amino-1,2,3-triazole-4-carbonitriles (3)) and selected cycloalkanones (4) of five-, six-, and seven-membered rings.

Diphenyl Diselenide and SARS-CoV-2: Exploration of the Mechanisms of Inhibition of Main Protease (M) and Papain-like Protease (PL).

The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (M) and the papain-like protease (PL) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe) which is an archetypal model of diselenides and a renowned potential therapeutic agent.

analysis of the antidepressant fluoxetine and similar drugs as inhibitors of the human protein acid sphingomyelinase: a related SARS-CoV-2 inhibition pathway.

Acid Sphingomyelinase (ASM) is a human phosphodiesterase that catalyzes the metabolism of sphingomyelin (SM) to ceramide and phosphocholine. ASM is involved in the plasma membrane cell repair and is associated with the lysosomal inner lipid membrane by nonbonding interactions. The disruption of those interaction would result in ASM release into the lysosomal lumen and consequent degradation of its structure.

Reactivity and binding mode of disulfiram, its metabolites, and derivatives in SARS-CoV-2 PL: insights from computational chemistry studies.

The papain-like protease (PL) from SARS-CoV-2 is an important target for the development of antivirals against COVID-19. The safe drug disulfiram (DSF) presents antiviral activity inhibiting PL in vitro, and it is under clinical trial studies, indicating to be a promising anti-COVID-19 drug. In this work, we aimed to understand the mechanism of PL inhibition by DSF and verify if DSF metabolites and derivatives could be potential inhibitors too.

Analysis of the Antidepressant Fluoxetine and Related Drugs at SARS-CoV-2 Main Protease (M) and Papain-like Protease (PL).

Background: SARS-CoV-2 main protease (M or 3CL) and papain-like protease (PL) are common viral targets for repurposed drugs to combat COVID-19 disease. Recently, several antidepressants (such as fluoxetine, venlafaxine and citalopram) belonging to the Selective Serotonin Reuptake Inhibitors (SSRIs) and the Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) classes have been shown to in vitro inhibit viral replication.

Aim: Investigate a possible action of fluoxetine and derivatives on SARS-CoV-2 protease sites.

In the Chalcogenoxide Elimination Panorama: Systematic Insight into a Key Reaction.

The selenoxide elimination is a well-known reaction in organochalcogen chemistry, with wide synthetic, biological, and toxicological implications. In this work, we apply benchmarked density functional theory (DFT) calculations to investigate different aspects of the title reaction in three (bio)chemically relevant models, spanning minimal systems of theoretical interests as well as biological or synthetic organochalcogenides. The activation strain analysis (ASA) methodology is employed along a suitable reaction coordinate to obtain insight into the role of the chalcogen and of the oxidation state, to pinpoint the factors that tune the elimination reactivity of the investigated systems.

Bromo-Substituted Diazenyl-pyrazolo[1,5-a]pyrimidin-2-amines: Sonogashira Cross-Coupling Reaction, Photophysical Properties, Bio-interaction and HSA Light-Up Sensor.

A convenient synthesis of a broad series of thirteen examples of alkyne-spacer derivatives 2 from the well-known Sonogashira cross-coupling reaction on diazenyl-pyrazolo[1,5-a]pyrimidin-2-amine compounds 1 is reported. The reactivity of heterocycles 1 due the presence of selected electron-donor (EDG) and electron-withdrawing (EWG) groups attached to different alkynes was evaluated. Also, the reactional versatility due the position variation of the bromo atom at the scaffolds 1 was also investigated.

Toxic metals that interact with thiol groups and alteration in insect behavior.

Toxic metals, such as mercury (Hg), lead (Pb), cadmium (Cd), and copper (Cu), are widespread in the biosphere, and human activities have contributed to their continuous release into the ecosystems. Metal-induced toxicity has been extensively studied in mammals; however, the effects of these metals on insects' behavior have been explored to far lesser degree. As the main mechanism of toxicity, the cationic metals, explored in this review, have high affinity for thiol-containing molecules, disrupting the function of several proteins and low-molecular-weight thiol-containing molecules.

One-Pot Synthesis and in Silico Molecular Docking Studies of Arylselanyl Hydrazides as Potential Antituberculosis Agents.

The present study reports a simple two-step method for the synthesis of arylselanyl hydrazide derivatives using hypophosphorous acid and polyethylene glycol (H PO /PEG-400) as an alternative reducing system and hydrazine hydrate (NH NH ⋅xH O/50-60 %). This single-vessel procedure was employed with methyl acrylate 2a and methyl bromoacetate 2b using diaryl diselenides to generate the nucleophile species to produce, respectively, 3-(arylselanyl)propane-hydrazides 4a-e and 2-(arylselanyl)acetohydrazides 5a-e with good yields by accelerating the reduction of -Se-Se- bond, when compared to available methods. The synthesized molecules are structurally similar to the isoniazid (INH).

Interaction Study between ESIPT Fluorescent Lipophile-Based Benzazoles and BSA.

In this study, the interactions of ESIPT fluorescent lipophile-based benzazoles with bovine serum albumin (BSA) were studied and their binding affinity was evaluated. In phosphate-buffered saline (PBS) solution these compounds produce absorption maxima in the UV region and a main fluorescence emission with a large Stokes shift in the blue-green regions due to a proton transfer process in the excited state. The interactions of the benzazoles with BSA were studied using UV-Vis absorption and steady-state fluorescence spectroscopy.

Methylmercury Can Facilitate the Formation of Dehydroalanine in Selenoenzymes: Insight from DFT Molecular Modeling.

Experimental studies have indicated that electrophilic mercury forms (e.g., methylmercury, MeHg) can accelerate the breakage of selenocysteine .

In silico Studies on the Interaction between Mpro and PLpro From SARS-CoV-2 and Ebselen, its Metabolites and Derivatives.

The COVID-19 pandemic caused by the SARS-CoV-2 has mobilized scientific attention in search of a treatment. The cysteine-proteases, main protease (Mpro) and papain-like protease (PLpro) are important targets for antiviral drugs. In this work, we simulate the interactions between the Mpro and PLpro with Ebselen, its metabolites and derivatives with the aim of finding molecules that can potentially inhibit these enzymes.

Effect of Methylmercury Binding on the Peroxide-Reducing Potential of Cysteine and Selenocysteine.

Methylmercury (CHHg) binding to catalytically fundamental cysteine and selenocysteine of peroxide-reducing enzymes has long been postulated as the origin of its toxicological activity. Only very recently, CHHg binding to the selenocysteine of thioredoxin reductase has been directly observed [Pickering, I. J.

7-Amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes]: Synthesis and cholinesterase inhibitory activity of structurally modified tacrines.

Five new examples of 9,10-chloro(bromo)-7-amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes] - in which cycloalkanes = cyclopentane, cyclohexane, and cycloheptane - were synthesized at yields of 42-56%, using a sequential one-pot two-step cyclocondensation reaction of three different scaffolds of 2-aminobenzonitriles and the respective spiro[chroman-2,1'-cycloalkan]-4-ones, and using AlCl as the catalyst in a solvent-free method. Subsequently, the five new spirochromeno-quinolines and nine quinolines previously published by us (14 modified tacrine scaffolds) were subjected to AChE and BChE inhibitory activity evaluation. The molecule containing a spirocyclopentane derivative had the highest AChE and BChE inhibitory activity (IC = 3.

Effects of CATECHIN on reserpine-induced vacuous chewing movements: behavioral and biochemical analysis.

This study evaluated the effect of (+)-catechin, a polyphenolic compound, on orofacial dyskinesia (OD) induced by reserpine in mice. The potential modulation of monoaminoxidase (MAO) activity, tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD) immunoreactivity by catechin were used as biochemical endpoints. The interaction of catechin with MAO-A and MAO-B was determined in vitro and in silico.