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Ebselen, a multi-target compound: its effects on biological processes and diseases

Published online by Cambridge University Press:  20 September 2021

Qianqian Lu ,
Yi Cai ,
Chenyan Xiang ,
Tao Wu ,
Ying Zhao ,
Jun Wang ,
Helen Wang  and
Lili Zou Open the ORCID record for Lili Zou [Opens in a new window]
Qianqian Lu
Affiliation:
The Central laboratory, The People’s Hospital of China Three Gorges University, 443002 Yichang, Hubei Province, China The Institute of Infection and Inflammation, Medical College, China Three Gorges University, 443002 Yichang, China
Yi Cai
Affiliation:
The Central laboratory, The People’s Hospital of China Three Gorges University, 443002 Yichang, Hubei Province, China The Institute of Infection and Inflammation, Medical College, China Three Gorges University, 443002 Yichang, China
Chenyan Xiang
Affiliation:
The Central laboratory, The People’s Hospital of China Three Gorges University, 443002 Yichang, Hubei Province, China
Tao Wu
Affiliation:
Chongqing Academy of Animal Science, 408599 Chongqing, China
Ying Zhao
Affiliation:
School of Pharmaceutical Sciences, Southwest University, 400715 Chongqing, China
Jun Wang*
Affiliation:
The Central laboratory, The People’s Hospital of China Three Gorges University, 443002 Yichang, Hubei Province, China
Helen Wang*
Affiliation:
Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden
Lili Zou*
Affiliation:
The Central laboratory, The People’s Hospital of China Three Gorges University, 443002 Yichang, Hubei Province, China The Institute of Infection and Inflammation, Medical College, China Three Gorges University, 443002 Yichang, China
*
Author for correspondence: Jun Wang, E-mail: [email protected]; Helen Wang, E-mail: [email protected]; Lili Zou, E-mail: [email protected]
Author for correspondence: Jun Wang, E-mail: [email protected]; Helen Wang, E-mail: [email protected]; Lili Zou, E-mail: [email protected]
Author for correspondence: Jun Wang, E-mail: [email protected]; Helen Wang, E-mail: [email protected]; Lili Zou, E-mail: [email protected]
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Abstract

Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.

Keywords

Antioxidantbiological processebselenmultiple targets
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e12
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Parnham, MJ and Sies, H (2013) The early research and development of ebselen. Biochemical Pharmacology 86, 1248–1253.CrossRefGoogle ScholarPubMed
Sakurai, T et al. (2006) Ebselen, a seleno-organic antioxidant, as an electrophile. Chemical Research in Toxicology 19, 1196–1204.CrossRefGoogle ScholarPubMed
Noguchi, N (2016) Ebselen, a useful tool for understanding cellular redox biology and a promising drug candidate for use in human diseases. Archives of Biochemistry and Biophysics 595, 109–112.CrossRefGoogle Scholar
Yang, CF, Shen, HM and Ong, CN (2000) Ebselen induces apoptosis in HepG(2) cells through rapid depletion of intracellular thiols. Archives of Biochemistry and Biophysics 374, 142–152.CrossRefGoogle ScholarPubMed
Pereira, CV et al. (2012) The contribution of oxidative stress to drug-induced organ toxicity and its detection in vitro and in vivo. Expert Opinion on Drug Metabolism & Toxicology 8, 219–237.CrossRefGoogle ScholarPubMed
Oliveira, PVS and Laurindo, FRM (2018) Implications of plasma thiol redox in disease. Clinical Science 132, 1257–1280.CrossRefGoogle Scholar
Niemeyer, BA (2017) The STIM-Orai pathway: regulation of STIM and Orai by thiol modifications. Advances in Experimental Medicine and Biology 993, 99–116.CrossRefGoogle ScholarPubMed
Hansen, JM and Harris, C (2015) Glutathione during embryonic development. Biochimica et Biophysica Acta 1850, 1527–1542.CrossRefGoogle ScholarPubMed
Lv, H et al. (2019) Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxidative Medicine and Cellular Longevity 2019, 3150145.CrossRefGoogle ScholarPubMed
Arteel, GE and Sies, H (2001) The biochemistry of selenium and the glutathione system. Environmental Toxicology and Pharmacology 10, 153–158.CrossRefGoogle ScholarPubMed
Yang, CF, Shen, HM and Ong, CN (2000) Intracellular thiol depletion causes mitochondrial permeability transition in ebselen-induced apoptosis. Archives of Biochemistry and Biophysics 380, 319–330.CrossRefGoogle ScholarPubMed
Ghareeb, H and Metanis, N (2020) The thioredoxin system: a promising target for cancer drug development. Chemistry 26, 10175–10184.CrossRefGoogle ScholarPubMed
Nordberg, J and Arnér, ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radical Biology & Medicine 31, 1287–1312.CrossRefGoogle ScholarPubMed
Xie, W et al. (2019) Overview of thioredoxin system and targeted therapies for acute leukemia. Mitochondrion 47, 38–46.CrossRefGoogle ScholarPubMed
Li, W et al. (2012) Two thioredoxin reductases, trxr-1 and trxr-2, have differential physiological roles in Caenorhabditis elegans. Molecules and Cells 34, 209–218.CrossRefGoogle ScholarPubMed
Marshall, AC et al. (2019) Structure, mechanism, and inhibition of Aspergillus fumigatus thioredoxin reductase. Antimicrobial Agents and Chemotherapy 63, e02281–2318.CrossRefGoogle ScholarPubMed
Ren, X et al. (2018) Selenocysteine in mammalian thioredoxin reductase and application of ebselen as a therapeutic. Free Radical Biology & Medicine 127, 238–247.CrossRefGoogle ScholarPubMed
May, HC et al. (2018) Repurposing auranofin, ebselen, and PX-12 as antimicrobial agents targeting the thioredoxin system. Frontiers in Microbiology 9, 336.CrossRefGoogle ScholarPubMed
Gustafsson, TN et al. (2016) Ebselen and analogs as inhibitors of Bacillus anthracis thioredoxin reductase and bactericidal antibacterials targeting Bacillus species, Staphylococcus aureus and Mycobacterium tuberculosis. Biochimica et Biophysica Acta 1860, 1265–1271.CrossRefGoogle ScholarPubMed
Xu, L et al. (2018) Ebselen suppresses inflammation induced by Helicobacter pylori lipopolysaccharide via the p38 mitogen-activated protein kinase signaling pathway. Molecular Medicine Reports 17, 6847–6851.Google ScholarPubMed
Bi, CL et al. (2016) Selenium inhibits Staphylococcus aureus-induced inflammation by suppressing the activation of the NF-κB and MAPK signalling pathways in RAW264.7 macrophages. European Journal of Pharmacology 780, 159–165.CrossRefGoogle ScholarPubMed
Sharma, A et al. (2016) Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium. Vascular Pharmacology 79, 32–42.CrossRefGoogle ScholarPubMed
Hilchie, AL et al. (2010) Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria. Nutrition and Cancer 62, 379–389.CrossRefGoogle Scholar
Yoshizumi, M et al. (2002) Ebselen attenuates oxidative stress-induced apoptosis via the inhibition of the c-Jun N-terminal kinase and activator protein-1 signalling pathway in PC12 cells. British Journal of Pharmacology 136, 1023–1032.CrossRefGoogle ScholarPubMed
Kim, SJ et al. (2009) Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells. Hearing Research 251, 70–82.CrossRefGoogle ScholarPubMed
Li, Y et al. (2019) Ebselen rescues oxidative-stress-suppressed osteogenic differentiation of bone-marrow-derived mesenchymal stem cells via an antioxidant effect and the PI3K/Akt pathway. Journal of Trace Elements in Medicine and Biology 55, 64–70.CrossRefGoogle ScholarPubMed
Thabet, NM and Moustafa, EM (2017) Synergistic effect of ebselen and gamma radiation on breast cancer cells. International Journal of Radiation Biology 93, 784–792.CrossRefGoogle ScholarPubMed
Boireau, A et al. (2000) The anti-oxidant ebselen antagonizes the release of the apoptogenic factor cytochrome c induced by Fe2+/citrate in rat liver mitochondria. Neuroscience Letters 289, 95–98.CrossRefGoogle ScholarPubMed
Laird, MD et al. (2008) Hemin-induced necroptosis involves glutathione depletion in mouse astrocytes. Free Radical Biology & Medicine 45, 1103–1114.CrossRefGoogle ScholarPubMed
Wei, L et al. (2014) Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway. Clinical and Experimental Pharmacology and Physiology 41, 134–138.CrossRefGoogle ScholarPubMed
Park, S et al. (2014) Ebselen pretreatment attenuates ischemia/reperfusion injury and prevents hyperglycemia by improving hepatic insulin signaling and β-cell survival in gerbils. Free Radical Research 48, 864–874.CrossRefGoogle ScholarPubMed
Park, IH et al. (2012) Role of reactive oxygen species in transforming growth factor beta1-induced alpha smooth-muscle actin and collagen production in nasal polyp-derived fibroblasts. International Archives of Allergy and Immunology 159, 278–286.CrossRefGoogle ScholarPubMed
Shi, H et al. (2006) Ebselen induced C6 glioma cell death in oxygen and glucose deprivation. Chemical Research in Toxicology 19, 655–660.CrossRefGoogle ScholarPubMed
Oostwoud, LC et al. (2016) Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice. Scientific Reports 6, 20983.CrossRefGoogle ScholarPubMed
Garland, M et al. (2020) The clinical drug ebselen attenuates inflammation and promotes microbiome recovery in mice after antibiotic treatment for CDI. Cell Reports Medicine 1, 100005.CrossRefGoogle ScholarPubMed
Lynch, ED et al. (2005) Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin toxicities in rat breast and ovarian cancer models while enhancing anti-tumor activity. Anti-Cancer Drugs 16, 569–579.CrossRefGoogle ScholarPubMed
Soyman, Z et al. (2018) Can ebselen prevent cisplatin-induced ovarian damage? Archives of Gynecology and Obstetrics 297, 1549–1555.CrossRefGoogle ScholarPubMed
Beckman, JA et al. (2016) Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial. American Journal of Physiology. Heart and Circulatory Physiology 311, H1431–h1436.CrossRefGoogle Scholar
Sharpley, AL et al. (2020) A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania. Psychopharmacology (Berl) 237, 3773–3782.CrossRefGoogle ScholarPubMed
Singh, N et al. (2016) Effect of the putative lithium mimetic ebselen on brain myo-inositol, sleep, and emotional processing in humans. Neuropsychopharmacology 41, 1768–1778.CrossRefGoogle ScholarPubMed
Kil, J et al. (2017) Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 390, 969–979.CrossRefGoogle ScholarPubMed
Yoshizumi, M et al. (2004) Ebselen inhibits tumor necrosis factor-alpha-induced c-Jun N-terminal kinase activation and adhesion molecule expression in endothelial cells. Experimental Cell Research 292, 1–10.CrossRefGoogle ScholarPubMed
Vera, M et al. (2018) Antioxidant and anti-inflammatory strategies based on the potentiation of glutathione peroxidase activity prevent endothelial dysfunction in chronic kidney disease. Cellular Physiology and Biochemistry 51, 1287–1300.CrossRefGoogle ScholarPubMed
Thangamani, S, Younis, W and Seleem, MN (2015) Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections. Scientific Reports 5, 11596.CrossRefGoogle ScholarPubMed
Thangamani, S, Younis, W and Seleem, MN (2015) Repurposing clinical molecule ebselen to combat drug resistant pathogens. PLoS ONE 10, e0133877.CrossRefGoogle ScholarPubMed
Chen, C and Yang, K (2019) Ebselen bearing polar functionality: identification of potent antibacterial agents against multidrug-resistant Gram-negative bacteria. Bioorganic Chemistry 93, 103286.CrossRefGoogle ScholarPubMed
Zou, L et al. (2017) Synergistic antibacterial effect of silver and ebselen against multidrug-resistant Gram-negative bacterial infections. EMBO Molecular Medicine 9, 1165–1178.CrossRefGoogle ScholarPubMed
Thangamani, S et al. (2017) Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells. Biochimica et Biophysica Acta General Subjects 1861, 3002–3010.CrossRefGoogle ScholarPubMed
Felli Kubica, T et al. (2019) In vitro activity of diphenyl diselenide and ebselen alone and in combination with antifungal agents against Trichosporon asahii. Mycoses 62, 428–433.CrossRefGoogle ScholarPubMed
Eltahan, R et al. (2019) The action of the hexokinase inhibitor 2-deoxy-d-glucose on Cryptosporidium parvum and the discovery of activities against the parasite hexokinase from marketed drugs. Journal of Eukaryotic Microbiology 66, 460–468.CrossRefGoogle ScholarPubMed
Thenin-Houssier, S et al. (2016) Ebselen, a small-molecule capsid inhibitor of HIV-1 replication. Antimicrobial Agents and Chemotherapy 60, 2195–2208.CrossRefGoogle ScholarPubMed
Martini, F et al. (2019) A multifunctional compound ebselen reverses memory impairment, apoptosis and oxidative stress in a mouse model of sporadic Alzheimer's disease. Journal of Psychiatric Research 109, 107–117.CrossRefGoogle Scholar
Klann, IP et al. (2020) Ebselen reversed peripheral oxidative stress induced by a mouse model of sporadic Alzheimer's disease. Molecular Biology Reports 47, 2205–2215.CrossRefGoogle ScholarPubMed
Antoniadou, I et al. (2018) Ebselen has lithium-like effects on central 5-HT2A receptor function. British Journal of Pharmacology 175, 2599–2610.CrossRefGoogle ScholarPubMed
Sui, H et al. (2005) Protective effect of antioxidant ebselen (PZ51) on the cerebral cortex of stroke-prone spontaneously hypertensive rats. Hypertension Research 28, 249–254.CrossRefGoogle ScholarPubMed
Imai, H et al. (2003) Antioxidant ebselen reduces oxidative damage in focal cerebral ischemia. Free Radical Biology & Medicine 34, 56–63.CrossRefGoogle ScholarPubMed
Wang, P et al. (2020) Depletion of multidrug-resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion. Journal of Cellular and Molecular Medicine 24, 13139–13150.CrossRefGoogle ScholarPubMed
Yamaguchi, T et al. (1998) Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke 29, 12–17.CrossRefGoogle ScholarPubMed
Ogawa, A et al. (1999) Ebselen in acute middle cerebral artery occlusion: a placebo-controlled, double-blind clinical trial. Cerebrovascular Diseases 9, 112–118.CrossRefGoogle ScholarPubMed
Wang, H et al. (2018) Sequence-based prediction of cysteine reactivity using machine learning. Biochemistry 57, 451–460.CrossRefGoogle ScholarPubMed
Poole, LB (2015) The basics of thiols and cysteines in redox biology and chemistry. Free Radical Biology & Medicine 80, 148–157.CrossRefGoogle ScholarPubMed
Backus, KM (2019) Applications of reactive cysteine profiling. Current Topics in Microbiology and Immunology 420, 375–417.Google ScholarPubMed
Maurais, AJ and Weerapana, E (2019) Reactive-cysteine profiling for drug discovery. Current Opinion in Chemical Biology 50, 29–36.CrossRefGoogle ScholarPubMed
Azad, GK et al. (2014) Ebselen induces reactive oxygen species (ROS)-mediated cytotoxicity in Saccharomyces cerevisiae with inhibition of glutamate dehydrogenase being a target. FEBS Open Bio 4, 77–89.CrossRefGoogle ScholarPubMed
Terentis, AC et al. (2010) The selenazal drug ebselen potently inhibits indoleamine 2,3-dioxygenase by targeting enzyme cysteine residues. Biochemistry 49, 591–600.CrossRefGoogle ScholarPubMed
Lieberman, OJ et al. (2014) High-throughput screening using the differential radial capillary action of ligand assay identifies ebselen as an inhibitor of diguanylate cyclases. ACS Chemical Biology 9, 183–192.CrossRefGoogle ScholarPubMed
Capper, MJ et al. (2018) The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation. Nature Communications 9, 1693.CrossRefGoogle ScholarPubMed
Chantadul, V et al. (2020) Ebselen as template for stabilization of A4V mutant dimer for motor neuron disease therapy. Communications Biology 3, 97.CrossRefGoogle ScholarPubMed
Chen, C et al. (2018) A protein structure-guided covalent scaffold selectively targets the B1 and B2 subclass metallo-beta-lactamases. Chemical Communications 54, 4802–4805.CrossRefGoogle ScholarPubMed
Chiou, J et al. (2015) Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1). Chemical Communications 51, 9543–9546.CrossRefGoogle Scholar
Hanavan, PD et al. (2015) Ebselen inhibits QSOX1 enzymatic activity and suppresses invasion of pancreatic and renal cancer cell lines. Oncotarget 6, 18418–18428.CrossRefGoogle ScholarPubMed
Joice, AC et al. (2013) Exploring the mode of action of ebselen in Trypanosoma brucei hexokinase inhibition. International Journal for Parasitology. Drugs and Drug Resistance 3, 154–160.CrossRefGoogle ScholarPubMed
Leroux, F et al. (2019) Identification of ebselen as a potent inhibitor of insulin degrading enzyme by a drug repurposing screening. European Journal of Medicinal Chemistry 179, 557–566.CrossRefGoogle ScholarPubMed
Jin, Z et al. (2020) Structure of M(pro) from COVID-19 virus and discovery of its inhibitors. Nature 582, 289–293.CrossRefGoogle ScholarPubMed
Sies, H and Parnham, MJ (2020) Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections. Free Radical Biology & Medicine 156, 107–112.CrossRefGoogle ScholarPubMed
Menéndez, CA et al. (2020) Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease. Science Advances 6, eabd0345.CrossRefGoogle ScholarPubMed
Anand, K et al. (2002) Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain. EMBO Journal 21, 3213–3224.CrossRefGoogle ScholarPubMed
Yang, H et al. (2003) The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proceedings of the National Academy of Sciences of the USA 100, 13190–13195.CrossRefGoogle ScholarPubMed
Weglarz-Tomczak, E et al. (2021) Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2. Scientific Reports 11, 3640.CrossRefGoogle ScholarPubMed
Kovacs-Nolan, J et al. (2014) In vitro and ex vivo uptake of glutathione (GSH) across the intestinal epithelium and fate of oral GSH after in vivo supplementation. Journal of Agricultural and Food Chemistry 62, 9499–9506.CrossRefGoogle ScholarPubMed
Xiao, Z et al. (2019) Molecular mechanisms of glutaredoxin enzymes: versatile hubs for thiol-disulfide exchange between protein thiols and glutathione. Journal of Molecular Biology 431, 158–177.CrossRefGoogle ScholarPubMed
Ren, X, Zou, L and Holmgren, A (2020) Targeting bacterial antioxidant systems for antibiotics development. Current Medicinal Chemistry 27, 1922–1939.CrossRefGoogle ScholarPubMed
Al-Brakati, AY et al. (2019) Role of thymoquinone and ebselen in the prevention of sodium arsenite-induced nephrotoxicity in female rats. Human & Experimental Toxicology 38, 482–493.CrossRefGoogle ScholarPubMed
Mohammed, AT, Ebraheim, LLM and Metwally, MMM (2018) Ebselen can protect male reproductive organs and male fertility from manganese toxicity: structural and bioanalytical approach in a Rat model. Biomedicine & Pharmacotherapy 102, 739–748.CrossRefGoogle ScholarPubMed
Baljinnyam, E et al. (2006) Oral pretreatment with ebselen enhances heat shock protein 72 expression and reduces myocardial infarct size. Hypertension Research 29, 905–913.CrossRefGoogle ScholarPubMed
Meinerz, DF et al. (2017) Diphenyl diselenide protects against methylmercury-induced inhibition of thioredoxin reductase and glutathione peroxidase in human neuroblastoma cells: a comparison with ebselen. Journal of Applied Toxicology 37, 1073–1081.CrossRefGoogle ScholarPubMed
Yu, Y et al. (2017) Ebselen: mechanisms of glutamate dehydrogenase and glutaminase enzyme inhibition. ACS Chemical Biology 12, 3003–3011.CrossRefGoogle ScholarPubMed
Lu, J et al. (2013) Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione. FASEB Journal 27, 1394–1403.CrossRefGoogle ScholarPubMed
Sandalova, T et al. (2001) Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proceedings of the National Academy of Sciences of the USA 98, 9533–9538.CrossRefGoogle ScholarPubMed
Zhao, R and Holmgren, A (2002) A novel antioxidant mechanism of ebselen involving ebselen diselenide, a substrate of mammalian thioredoxin and thioredoxin reductase. Journal of Biological Chemistry 277, 39456–39462.CrossRefGoogle ScholarPubMed
Dong, C et al. (2019) Topical therapeutic efficacy of ebselen against multidrug-resistant Staphylococcus aureus LT-1 targeting thioredoxin reductase. Frontiers in Microbiology 10, 3016.CrossRefGoogle ScholarPubMed
Maqbool, I et al. (2019) Understanding the survival mechanisms of Deinococcus radiodurans against oxidative stress by targeting thioredoxin reductase redox system. Archives of Microbiology 202, 2355–2366.CrossRefGoogle ScholarPubMed
Kumar, V (2019) Inflammation research sails through the sea of immunology to reach immunometabolism. International Immunopharmacology 73, 128–145.CrossRefGoogle ScholarPubMed
Sun, SC (2017) The non-canonical NF-κB pathway in immunity and inflammation. Nature Reviews Immunology 17, 545–558.CrossRefGoogle ScholarPubMed
Huang, X et al. (2018) Sinapic acid inhibits the IL-1β-induced inflammation via MAPK downregulation in rat chondrocytes. Inflammation 41, 562–568.CrossRefGoogle ScholarPubMed
Belvisi, MG et al. (2000) Anti-inflammatory properties of ebselen in a model of sephadex-induced lung inflammation. European Respiratory Journal 15, 579–581.CrossRefGoogle Scholar
Sarker, KP et al. (2003) Ebselen inhibits NO-induced apoptosis of differentiated PC12 cells via inhibition of ASK1-p38 MAPK-p53 and JNK signaling and activation of p44/42 MAPK and Bcl-2. Journal of Neurochemistry 87, 1345–1353.CrossRefGoogle ScholarPubMed
Ali, N et al. (2004) Ebselen inhibits p38 mitogen-activated protein kinase-mediated endothelial cell death by hydrogen peroxide. European Journal of Pharmacology 485, 127–135.CrossRefGoogle ScholarPubMed
Azad, GK and Tomar, RS (2014) Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways. Molecular Biology Reports 41, 4865–4879.CrossRefGoogle ScholarPubMed
Jia, ZQ et al. (2018) Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury. Neuroscience Letters 678, 110–117.CrossRefGoogle ScholarPubMed
Leuti, A, Maccarrone, M and Chiurchiù, V (2019) Proresolving lipid mediators: endogenous modulators of oxidative stress. Oxidative Medicine and Cellular Longevity 2019, 8107265.Google ScholarPubMed
Lee, RL, Westendorf, J and Gold, MR (2007) Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4. Journal of Cell Communication and Signaling 1, 33–43.CrossRefGoogle Scholar
Yan, BC et al. (2012) Comparison of inflammatory cytokines changes in the hippocampal CA1 region between the young and adult gerbil after transient cerebral ischemia. Brain Research 1461, 64–75.CrossRefGoogle Scholar
Tak, JK and Park, JW (2009) The use of ebselen for radioprotection in cultured cells and mice. Free Radical Biology & Medicine 46, 1177–1185.CrossRefGoogle ScholarPubMed
Nishina, A et al. (2008) Ebselen, a redox regulator containing a selenium atom, induces neurofilament M expression in cultured rat pheochromocytoma PC12 cells via activation of mitogen-activated protein kinase. Journal of Neuroscience Research 86, 720–725.CrossRefGoogle ScholarPubMed
Baek, JM et al. (2016) Ebselen is a potential anti-osteoporosis agent by suppressing receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation in vitro and lipopolysaccharide-induced inflammatory bone destruction in vivo. International Journal of Biological Sciences 12, 478–488.CrossRefGoogle ScholarPubMed
Steinbrenner, H, Speckmann, B and Klotz, LO (2016) Selenoproteins: antioxidant selenoenzymes and beyond. Archives of Biochemistry and Biophysics 595, 113–119.CrossRefGoogle ScholarPubMed
Allingstrup, M and Afshari, A (2015) Selenium supplementation for critically ill adults. The Cochrane Database of Systematic Reviews 2015, Cd003703.Google Scholar
Marthandan, S et al. (2013) An investigation of the effects of the antioxidants, ebselen or N-acetyl cysteine on human peripheral blood mononuclear cells and T cells. Immunity & Ageing: I & A 10, 7.CrossRefGoogle ScholarPubMed
Lane, CA, Hardy, J and Schott, JM (2018) Alzheimer's disease. European Journal of Neurology 25, 59–70.CrossRefGoogle ScholarPubMed
Luo, Z et al. (2014) Synthesis and biological evaluation of a new series of ebselen derivatives as glutathione peroxidase (GPx) mimics and cholinesterase inhibitors against Alzheimer's disease. Bioorganic & Medicinal Chemistry 22, 1355–1361.CrossRefGoogle ScholarPubMed
Xie, Y et al. (2017) Ebselen ameliorates β-amyloid pathology, tau pathology, and cognitive impairment in triple-transgenic Alzheimer's disease mice. Journal of Biological Inorganic Chemistry: JBIC 22, 851–865.CrossRefGoogle ScholarPubMed
Xie, L et al. (2012) Ebselen inhibits iron-induced tau phosphorylation by attenuating DMT1 up-regulation and cellular iron uptake. Neurochemistry International 61, 334–340.CrossRefGoogle ScholarPubMed
Zesiewicz, TA (2019) Parkinson disease. Continuum 25, 896–918.Google ScholarPubMed
Tio, M et al. (2017) Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants. Human Mutation 38, 978–987.CrossRefGoogle ScholarPubMed
Angeles, DC et al. (2014) Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila. Human Molecular Genetics 23, 3157–3165.CrossRefGoogle ScholarPubMed
Oh-Hashi, K and Hirata, Y (2020) Elucidation of the molecular characteristics of wild-type and ALS-linked mutant SOD1 using the NanoLuc complementation reporter system. Applied Biochemistry and Biotechnology 190, 674–685.CrossRefGoogle ScholarPubMed
Randolph, SA (2016) Ischemic stroke. Workplace Health & Safety 64, 444.CrossRefGoogle ScholarPubMed
Martínez-Vila, ESP (2001) Current status and perspectives of neuroprotection in ischemic stroke treatment. Cerebrovascular Diseases 11, 60–70.CrossRefGoogle ScholarPubMed
Parnham, M and Sies, H (2000) Ebselen: prospective therapy for cerebral ischaemia. Expert Opinion on Investigational Drugs 9, 607–619.CrossRefGoogle ScholarPubMed
Yamagata, K et al. (2008) Protective effects of ebselen, a seleno-organic antioxidant on neurodegeneration induced by hypoxia and reperfusion in stroke-prone spontaneously hypertensive rat. Neuroscience 153, 428–435.CrossRefGoogle ScholarPubMed
Imai, HMH et al. (2001) Ebselen protects both gray and white matter in a rodent model of focal cerebral ischemia. Stroke 32, 2149–2154.CrossRefGoogle Scholar
Lapchak, PA and Zivin, JA (2003) Ebselen, a seleno-organic antioxidant, is neuroprotective after embolic strokes in rabbits: synergism with low-dose tissue plasminogen activator. Stroke 34, 2013–2018.CrossRefGoogle ScholarPubMed
Koizumi, H et al. (2011) Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide. Neurologia Medico-Chirurgica 51, 337–343.CrossRefGoogle ScholarPubMed
Seo, JY et al. (2009) Neuroprotection of ebselen against ischemia/reperfusion injury involves GABA shunt enzymes. Journal of the Neurological Sciences 285, 88–94.CrossRefGoogle ScholarPubMed
AbdelKhalek, A et al. (2018) Repurposing ebselen for decolonization of vancomycin-resistant enterococci (VRE). PLoS ONE 13, e0199710.CrossRefGoogle Scholar
Favrot, L et al. (2013) Mechanism of inhibition of Mycobacterium tuberculosis antigen 85 by ebselen. Nature Communications 4, 2748.CrossRefGoogle ScholarPubMed
Favrot, L, Lajiness, DH and Ronning, DR (2014) Inactivation of the Mycobacterium tuberculosis antigen 85 complex by covalent, allosteric inhibitors. Journal of Biological Chemistry 289, 25031–25040.CrossRefGoogle ScholarPubMed
Dong, C et al. (2020) Synergistic therapeutic efficacy of ebselen and silver ions against multidrug-resistant Acinetobacter baumannii-induced urinary tract infections. Metallomics: Integrated Biometal Science 12, 860–867.CrossRefGoogle ScholarPubMed
Harris, MT et al. (2013) Interrogating a hexokinase-selected small-molecule library for inhibitors of Plasmodium falciparum hexokinase. Antimicrobial Agents and Chemotherapy 57, 3731–3737.CrossRefGoogle ScholarPubMed
Santofimia-Castaño, P et al. (2014) The seleno-organic compound ebselen impairs mitochondrial physiology and induces cell death in AR42J cells. Toxicology Letters 229, 465–473.CrossRefGoogle ScholarPubMed
Zhang, L et al. (2014) Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production. Biomed Research International 2014, 696107.Google ScholarPubMed
Węglarz-Tomczak, EB-GM, Giurg, M and Mucha, A (2016) Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: synthesis, inhibitory activity and molecular modeling study. Bioorganic & Medicinal Chemistry Letters 26, 5254–5259.CrossRefGoogle ScholarPubMed
Sung, SY et al. (2006) Oxidative stress induces ADAM9 protein expression in human prostate cancer cells. Cancer Research 66, 9519–9526.CrossRefGoogle ScholarPubMed
Wilson, BA et al. (2011) High-throughput screen identifies novel inhibitors of cancer biomarker α-methylacyl coenzyme A racemase (AMACR/P504S). Molecular Cancer Therapeutics 10, 825–838.CrossRefGoogle Scholar
Wang, Y et al. (2017) Developing selective histone deacetylases (HDACs) inhibitors through ebselen and analogs. Drug Design, Development and Therapy 11, 1369–1382.CrossRefGoogle ScholarPubMed
Ardais, AP, Santos, FW and Nogueira, CW (2008) Ebselen attenuates cadmium-induced testicular damage in mice. Journal of Applied Toxicology 28, 322–328.CrossRefGoogle ScholarPubMed
Avila, DS et al. (2012) Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress. Free Radical Biology & Medicine 52, 1903–1910.CrossRefGoogle ScholarPubMed
Oliveira, CS et al. (2017) Chemical speciation of selenium and mercury as determinant of their neurotoxicity. Advances in Neurobiology 18, 53–83.CrossRefGoogle ScholarPubMed
Davis, MT and Bartfay, WJ (2004) Ebselen decreases oxygen free radical production and iron concentrations in the hearts of chronically iron-overloaded mice. Biological Research for Nursing 6, 37–45.CrossRefGoogle ScholarPubMed
Husain, K et al. (1998) Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant system. Molecular and Cellular Biochemistry 178, 127–133.CrossRefGoogle ScholarPubMed
Wilhelm, EABC, Jesse, CR and Luchese, C (2014) Ebselen protects against behavioral and biochemical toxicities induced by 3-nitropropionic acid in rats: correlations between motor coordination, reactive species levels, and succinate dehydrogenase activity. Biological Trace Element Research 162, 200–210.CrossRefGoogle ScholarPubMed
Lulla, APM et al. (2013) Ebselen reduces the toxicity of mechlorethamine in A-431 cells via inhibition of apoptosis. Journal of Biochemical and Molecular Toxicology 27, 313–322.CrossRefGoogle ScholarPubMed
Moretto, MB et al. (2005) Organoselenium compounds prevent hyperphosphorylation of cytoskeletal proteins induced by the neurotoxic agent diphenyl ditelluride in cerebral cortex of young rats. Toxicology 210, 213–222.CrossRefGoogle ScholarPubMed
Chen, X et al. (2019) Characterization of synergistic antibacterial effect of silver nanoparticles and ebselen. Artificial Cells, Nanomedicine, and Biotechnology 47, 3338–3349.CrossRefGoogle ScholarPubMed
Meotti, FC et al. (2003) Potential renal and hepatic toxicity of diphenyl diselenide, diphenyl ditelluride and ebselen for rats and mice. Toxicology Letters 143, 9–16.CrossRefGoogle ScholarPubMed
Farina, M et al. (2004) Additive pro-oxidative effects of methylmercury and ebselen in liver from suckling rat pups. Toxicology Letters 146, 227–235.CrossRefGoogle ScholarPubMed
Nie, Y et al. (2020) Synthesis and potential anti-cancer activity of some novel selenocyanates and diselenides. Chemistry and Biodiversity 17, e1900603.CrossRefGoogle Scholar
Kaczor-Keller, KB et al. (2020) In vitro anti-prostate cancer activity of two ebselen analogues. Pharmaceuticals (Basel) 13, 47.CrossRefGoogle ScholarPubMed