The Role of Selenium in Pathologies: An Updated Review

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 251 - 251

Published: Jan. 27, 2022

Selenium is an essential microelement required for a number of biological functions. Selenium-and more specifically the amino acid selenocysteine-is present in at least 25 human selenoproteins involved wide variety functions, ranging from regulation reactive oxygen species (ROS) concentration to biosynthesis hormones. These processes also play central role preventing and modulating clinical outcome several diseases, including cancer, diabetes, Alzheimer's disease, mental disorders, cardiovascular fertility impairments, inflammation, infections (including SARS-CoV-2). Over past years, studies focusing on relationship between selenium such pathologies have been reported. Generally, adequate nutritional state-and some cases supplementation-have related improved prognostic reduced risk developing diseases. On other hand, supra-nutritional levels might adverse effects. The results recent these topics are summarized discussed this review, with particular emphasis advances achieved last decade.

Language: Английский

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Synthesis and in Silico Investigation of Organoselenium-Clubbed Schiff Bases as Potential Mpro Inhibitors for the SARS-CoV-2 Replication

Life, Journal Year: 2023, Volume and Issue: 13(4), P. 912 - 912

Published: March 30, 2023

Since the first report of organoselenium compound, ebselen, as a potent inhibitor SARS-CoV-2 Mpro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) characterized using spectroscopic techniques. Their geometries studied DFT B3LYP/6-311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 used model pharmacophores interpret binding requirements inhibitors. The antiviral efficiency novel compounds was assessed molecular docking against 6LU7 protein investigate possible interactions. Our results showed that primary bound ligands with high energy scores ranging from -8.19 -7.33 Kcal/mol 4c 4a -6.10 -6.20 6b 6a. Furthermore, data are Moreover, drug-likeness studies, including Lipinski's rule ADMET properties, also assessed. Interestingly, candidates manifested solid pharmacokinetic qualities studies. Overall, demonstrated organoselenium-based might serve epidemic.

Language: Английский

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Selenization of Small Molecule Drugs: A New Player on the Board

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(10), P. 7759 - 7787

Published: May 8, 2024

There is an urgent need to develop safer and more effective modalities for the treatment of a wide range pathologies due increasing rates drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout years, selenium (Se) has attracted great deal attention its important role in human health. Besides, growing body work unveiled that inclusion Se motifs into number molecules promising strategy obtaining novel therapeutic agents. In current Perspective, we have gathered most recent literature related incorporation different moieties scaffolds known drugs their feasible pharmaceutical applications. addition, highlight representative examples as well provide our perspective on possible future directions, promises, opportunities, challenges this ground-breaking area research.

Language: Английский

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Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation

Molecules, Journal Year: 2021, Volume and Issue: 26(14), P. 4230 - 4230

Published: July 12, 2021

Ebselen is the leader of selenorganic compounds, and starting from its identification as mimetic key antioxidant enzyme glutathione peroxidase, several papers have appeared in literature claiming biological activities. It was subject clinical trials it currently evaluation for treatment COVID-19 patients. Given our interest synthesis pharmacological derivatives with this review, we aimed to collect all focused on ebselen close analogues, covering timeline between 2016 most 2021. Our analysis evidences that, even if lacks specificity when tested vitro, being able bind every reactive cysteine, proved be always well tolerated vivo, exerting no sign toxicity whatever administered doses. Besides, looking at literature, realized that review article dealing synthetic approaches construction benzo[

Language: Английский

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Electrochemical regioselective synthesis of N-substituted/unsubstituted 4-selanylisoquinolin-1(2H)-ones

Chinese Chemical Letters, Journal Year: 2021, Volume and Issue: 33(3), P. 1501 - 1504

Published: Aug. 19, 2021

Language: Английский

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Immunomodulatory and Anti-Inflammatory Properties of Selenium-Containing Agents: Their Role in the Regulation of Defense Mechanisms against COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(4), P. 2360 - 2360

Published: Feb. 21, 2022

The review presents the latest data on role of selenium-containing agents in regulation diseases immune system. We mainly considered contributions compounds such as sodium selenite, methylseleninic acid, selenomethionine, and methylselenocysteine, well selenoproteins selenium nanoparticles defense mechanisms against various viral infections, including coronavirus infection (COVID-19). A complete description available for each above underlying processes with active participation these agents, their therapeutic pharmacological potential, is presented. main purpose this to systematize information, supplemented by obtained our laboratory, important all processes. In addition, presented information makes it possible understand key differences action compounds, depending chemical physical properties, which obtaining a holistic picture prospects creating drugs based them.

Language: Английский

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Small-Molecule Ebselen Binds to YTHDF Proteins Interfering with the Recognition of N⁶-Methyladenosine-Modified RNAs

ACS Pharmacology & Translational Science, Journal Year: 2022, Volume and Issue: 5(10), P. 872 - 891

Published: Sept. 14, 2022

YTHDF proteins bind the N6-methyladenosine (m6A)-modified mRNAs, influencing their processing, stability, and translation. Therefore, members of this protein family play crucial roles in gene regulation several physiological pathophysiological conditions. contain a hydrophobic pocket that accommodates m6A embedded RRACH consensus sequence on mRNAs. We exploited presence cage to set up an m6A-competitive assay performed high-throughput screen aimed at identifying ligands binding pocket. report organoselenium compound ebselen as first-in-class inhibitor m6A-binding domain. Ebselen, whose interaction with was validated via orthogonal assays, cannot discriminate between domains three paralogs but can disrupt domain m6A-decorated mRNA targets. X-ray, mass spectrometry, NMR studies indicate YTHDF1 binds close cage, covalently Cys412 cysteine, or interacts reversibly depending reducing environment. also showed engages within cells, interfering binding. Finally, we produced series structural analogs interact domain, proving expansion is amenable for developing new inhibitors. Our work demonstrates feasibility drugging YTH opens avenues development disruptors recognition.

Language: Английский

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A Triterpenoid Lupeol as an Antioxidant and Anti-Neuroinflammatory Agent: Impacts on Oxidative Stress in Alzheimer’s Disease

Nutrients, Journal Year: 2023, Volume and Issue: 15(13), P. 3059 - 3059

Published: July 7, 2023

Alzheimer’s disease (AD) is the most common neurodegenerative illustrated by neuronal dysfunctions, leading to memory weaknesses and personality changes mostly in aged population worldwide. The exact cause of AD unclear, but numerous studies have addressed involvement oxidative stress (OS), induced reactive oxygen species (ROS), be one causes developing AD. OS dysregulates cellular homeostasis, causing abnormal protein lipid metabolism. Nutrition plays a pivotal role modulating antioxidant system decreases ROS level, thus playing an important therapeutic diseases, especially Hence, medicinal herbs their extracts received global attention as commercial source antioxidants Lupeol. Lupeol pentacyclic triterpenoid has many biological functions. It available fruits, vegetables, plants. shown effective anti-inflammatory properties, higher blood–brain barrier permeability. Also, binding inhibitory potentials been investigated proved against certain receptor proteins enzymes computational molecular docking approaches. Therefore, AD-related research gained interest investigating effects However, despite its beneficial AD, there still lack we compiled this analysis all preclinical that looked at agent for

Language: Английский

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Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PLpro and Mpro proteases, and nsp14 guanine N7-methyltransferase

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 6, 2023

Abstract Proteases encoded by SARS-CoV-2 constitute a promising target for new therapies against COVID-19. main protease (M pro , 3CL ) and papain-like (PL are responsible viral polyprotein cleavage—a process crucial survival replication. Recently it was shown that 2-phenylbenzisoselenazol-3(2 H )-one (ebselen), an organoselenium anti-inflammatory small-molecule drug, is potent, covalent inhibitor of both the proteases its potency evaluated in enzymatic antiviral assays. In this study, we screened collection 34 ebselen diselenide derivatives PL M inhibitors. Our studies revealed potent inhibitors proteases. We identified three four superior to ebselen. Independently, inhibit N7-methyltransferase activity nsp14 protein involved RNA cap modification. Hence, selected compounds were also as second part our work, employed 11 analogues—bis(2-carbamoylaryl)phenyl diselenides—in biological assays evaluate their anti-SARS-CoV-2 Vero E6 cells. present cytoprotective low cytotoxicity. work shows ebselen, derivatives, analogues platform development antivirals targeting virus.

Language: Английский

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Enlightening the Path to Protein Engineering: Chemoselective Turn-On Probes for High-Throughput Screening of Enzymatic Activity

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(6), P. 2832 - 2901

Published: Feb. 28, 2023

Many successful stories in enzyme engineering are based on the creation of randomized diversity large mutant libraries, containing millions to billions variants. Methods that enabled their evaluation with high throughput dominated by spectroscopic techniques due speed and sensitivity. A proportion studies relies fluorogenic substrates mimic chemical properties target or coupled enzymatic assays an optical read-out assesses desired catalytic efficiency indirectly. The most reliable hits, however, achieved screening for conversions starting material product. For this purpose, functional group offer a general approach achieve fast, read-out. They use chemoselectivity, differences electronic steric various groups, reduce number false-positive results analytical noise stemming from background activities. This review summarizes developments probes chemoselective derivatizations, clear focus activity protein engineering.

Language: Английский

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