Organoselenotriazoles attenuate oxidative damage induced by mitochondrial dysfunction in mev-1 Caenorhabditis elegans mutants

Soares, Ana Thalita Gonçalves; Rodrigues, Luiz Brasil Lopes; Salgueiro, Willian G.; Forno, Ana Helena de Castro Dal; Rodrigues, Cristiane Freitas; Sacramento, Manoela; Franco, Jeferson Luís; Alves, Diego; Oliveira, Riva de Paula; Pinton, Simone; Ávila, Daiana Silva

doi:10.1016/j.jtemb.2019.01.017

Cited by 15 publications

(13 citation statements)

References 50 publications

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“…SODs perform their bio-protective role by converting superoxide into molecular oxygen and hydrogen peroxide by cyclic redox reactions containing a metal (Mn, Zn, Cu or Fe) at the active site, and for this reason it is considered a molecular drug target (Azadmanesh & Borgstahl 2018, Bonetta 2017. The expression of these enzymes can be modulated by xenobiotics, and our group has been focused on investigating the molecular targets of molecules named organochalcogens (Wollenhaupt et al 2014, Avila et al 2012, Salgueiro et al 2017, Soares et al 2019.…”

Section: Introductionmentioning

confidence: 99%

Activation of SOD-3 is involved in the antioxidant effect of a new class of β-aryl-chalcogenium azide compounds in Caenorhabditis elegans

Motta

Roos

Tabarelli

et al. 2020

An. Acad. Bras. Ciênc.

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Organic selenium, tellurium and sulfur compounds have been studied due to their pharmacological properties. For instance, the β-aryl-chalcogenium azide compounds have demonstrated antitumoral action in vitro. However, yet no pharmacological actions of this class of compounds were determined in vivo.Caenorhabditis elegans is a nematode that presents innumerable advantages in relation to mammalian models, such as having a small and transparent body, which allows the visualization of its internal anatomy, besides short life and low cost. Based on that, the aim of this work was to investigate the pharmacological and toxicological properties of β-aryl-chalcogenium azide compounds in C. elegans. As well, to evaluate the capacity of organochalcogenium compounds to repair oxidative damage induced by hydrogen peroxide and the possible mechanism of action of these compounds using CF1553 transgenic strain with superoxide dismutase (SOD-3) tagged with GFP. Our results showed that β-aryl-chalcogenium azide have low toxicity in wild-type worms and the pre-treatment protected against the damage induced by hydrogen peroxide at higher tested concentration. Associated with this, we observed that this protection is due in part to the increased expression of the antioxidant enzyme SOD-3. In conclusion, β-arylchalcogenium azide compounds caused low toxicity and induced stress-resistance by modulating SOD-3 expression in C. elegans.

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Section: Introductionmentioning

confidence: 99%

Activation of SOD-3 is involved in the antioxidant effect of a new class of β-aryl-chalcogenium azide compounds in Caenorhabditis elegans

Motta

Roos

Tabarelli

et al. 2020

An. Acad. Bras. Ciênc.

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“…An in vivo study was conducted on a Caenorhabditis elegans worm model. Compared to the RSH "isoforms," the present molecules have great reducing potential [33]. found to be selective towards HDAC6.…”

Section: Selenium In Therapeutics Medicinal Chemistry and Skeleton Coresmentioning

confidence: 95%

“…An in vivo study was conducted on a Caenorhabditis elegans worm model. Compared to the RSH "isoforms," the present molecules have great reducing potential [33]. In relationship to H2S signaling, persulfides and selenosulfides and the R-SeSH motif containing compounds were importantly produced, studied and discussed by Kang et al The article by Soares et al is based on a series of organoselenotriazole compounds and the notion of mitochondrial dysfunction; the selenium-containing enzymes have selenium in the form of R-SeH groups (Figure 9).…”

Section: Selenium In Therapeutics Medicinal Chemistry and Skeleton Coresmentioning

confidence: 99%

“…An in vivo study was conducted on a Caenorhabditis elegans worm model. Compared to the RSH "isoforms," the present molecules have great reducing potential [33]. In relationship to H2S signaling, persulfides and selenosulfides and the R-SeSH motif containing compounds were importantly produced, studied and discussed by Kang et al In relationship to H 2 S signaling, persulfides and selenosulfides and the R-SeSH motif containing compounds were importantly produced, studied and discussed by Kang et al Mechanistic and reactivity work with Hantzsh's ester involves a model for NADH as well.…”

Section: Selenium In Therapeutics Medicinal Chemistry and Skeleton Coresmentioning

confidence: 99%

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Discussions of Fluorescence in Selenium Chemistry: Recently Reported Probes, Particles, and a Clearer Biological Knowledge

et al. 2021

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In this review from literature appearing over about the past 5 years, we focus on selected selenide reports and related chemistry; we aimed for a digestible, relevant, review intended to be usefully interconnected within the realm of fluorescence and selenium chemistry. Tellurium is mentioned where relevant. Topics include selenium in physics and surfaces, nanoscience, sensing and fluorescence, quantum dots and nanoparticles, Au and oxide nanoparticles quantum dot based, coatings and catalyst poisons, thin film, and aspects of solar energy conversion. Chemosensing is covered, whether small molecule or nanoparticle based, relating to metal ion analytes, H2S, as well as analyte sulfane (biothiols—including glutathione). We cover recent reports of probing and fluorescence when they deal with redox biology aspects. Selenium in therapeutics, medicinal chemistry and skeleton cores is covered. Selenium serves as a constituent for some small molecule sensors and probes. Typically, the selenium is part of the reactive, or active site of the probe; in other cases, it is featured as the analyte, either as a reduced or oxidized form of selenium. Free radicals and ROS are also mentioned; aggregation strategies are treated in some places. Also, the relationship between reduced selenium and oxidized selenium is developed.

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“…focused on developing prospective drug candidates [11][12][13][14][15][16][17][18][19][20] ; however, the most famous selenium drug candidate so far is ebselen, which contains Se-N bonds. It is a multifunctional compound that catalyzes several essential reactions (e.g., reduces reactive oxygen species (ROS) in a manner similar to glutathione peroxidase (GPx), and highly efficiently oxidizes reduced thioredoxin and catalyzes hydrogen peroxide reduction by thioredoxin reductase (TrxR), which acts as a dehydroascorbic acid (DHA) reductase mimetic) for the protection of cellular components from oxidative and free radical damage 21 .…”

mentioning

confidence: 99%

Fused isoselenazolium salts suppress breast cancer cell growth by dramatic increase in pyruvate-dependent mitochondrial ROS production

Makrecka-Kūka

Dimitrijevs

Домрачева

et al. 2020

Sci Rep

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The development of targeted drugs for the treatment of cancer remains an unmet medical need. This study was designed to investigate the mechanism underlying breast cancer cell growth suppression caused by fused isoselenazolium salts. The ability to suppress the proliferation of malignant and normal cells in vitro as well as the effect on NAD homeostasis (NAD+, NADH, and NMN levels), NAMPT inhibition and mitochondrial functionality were studied. The interactions of positively charged isoselenazolium salts with the negatively charged mitochondrial membrane model were assessed. Depending on the molecular structure, fused isoselenazolium salts display nanomolar to high micromolar cytotoxicities against MCF-7 and 4T1 breast tumor cell lines. The studied compounds altered NMN, NAD+, and NADH levels and the NAD+/NADH ratio. Mitochondrial functionality experiments showed that fused isoselenazolium salts inhibit pyruvate-dependent respiration but do not directly affect complex I of the electron transfer system. Moreover, the tested compounds induce an immediate dramatic increase in the production of reactive oxygen species. In addition, the isoselenazolothiazolium derivative selectively binds to cardiolipin in a liposomal model. Isoselenazolium salts may be a promising platform for the development of potent drug candidates for anticancer therapy that impact mitochondrial pyruvate-dependent metabolism in breast cancer cells.

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Organoselenotriazoles attenuate oxidative damage induced by mitochondrial dysfunction in mev-1 Caenorhabditis elegans mutants

Cited by 15 publications

References 50 publications

Activation of SOD-3 is involved in the antioxidant effect of a new class of β-aryl-chalcogenium azide compounds in Caenorhabditis elegans

Activation of SOD-3 is involved in the antioxidant effect of a new class of β-aryl-chalcogenium azide compounds in Caenorhabditis elegans

Discussions of Fluorescence in Selenium Chemistry: Recently Reported Probes, Particles, and a Clearer Biological Knowledge

Fused isoselenazolium salts suppress breast cancer cell growth by dramatic increase in pyruvate-dependent mitochondrial ROS production

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