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

Lu, Qianqian; Cai, Yi; Xiang, Chenyan; Wu, Tao; Zhao, Ying; Wang, Jun; Wang, Helen; Zou, Lili

doi:10.1017/erm.2021.14

Cited by 12 publications

(20 citation statements)

References 150 publications

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“…57 Bright yellow flakes, yield 54%, mp 241−242 °C (AcOEt). 1 H NMR (600.6 MHz, DMSO-d 6 ) δ 7.50 (ddd, J = 7.7, 7.5, 0.9 Hz, 1H), 7.71 (ddd, J = 8.0, 7.5, 1.4 Hz, 1H), 7.80 (d, J = 8.5 Hz, 2H), 7.94 (dd, J = 7.7, 1.4 Hz, 1H), 7.94 (d, J = 8.5 Hz, 2H), 8.10 (dd, J = 8.0, 0.9 Hz, 1H). 13 C NMR (100.5 MHz, DMSO-d 6 ) δ 124.08 (q, J = 271.8 Hz), 124.15, 125.24 (q, J = 32.3 Hz), 125.84, 126.25 (q, J = 3.7 Hz), 126.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Ebselen (2-phenyl-1,2-benzisoselenazol-3(2 H )-one, 1 ; Table 1 ) is an extensively studied antioxidant, anti-inflammatory, antiatherosclerotic, and cytoprotective organoselenium compound. 1 While these properties were originally attributed to a glutathione peroxidase-like activity of Ebselen, 2 − 4 the biomedical impact of this drug in living organisms has been shown to be much more complex. Accordingly, Ebselen and its metabolites react with hydroperoxides to protect cells from free-radical damage; 5 , 6 furthermore, Ebselen works as a substrate for thioredoxin reductase, 7 while the inhibition at low concentrations of a number of enzymes involved in inflammation, such as lipoxygenases, NO synthases, NADPH oxidase, and others, has also been well documented and reviewed.…”

Section: Introductionmentioning

confidence: 99%

“…Pale powder, yield 72%, mp 163−164 °C (H 2 O) 1. H NMR (300.1 MHz, DMSO-d 6 ) δ 2.32 (s, 3H), 7.24 (d, J = 8.1 Hz, 2H), 7.47−7.53 (m, 3H), 7.67 (ddd, J = 8.0, 7.5, 1.3 Hz, 1H), 7.90 (d, J = 7.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H) 13.…”

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confidence: 99%

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Optimized Ebselen-Based Inhibitors of Bacterial Ureases with Nontypical Mode of Action

et al. 2023

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Screening of 25 analogs of Ebselen, diversified at the N-aromatic residue, led to the identification of the most potent inhibitors of Sporosarcina pasteurii urease reported to date. The presence of a dihalogenated phenyl ring caused exceptional activity of these 1,2-benzisoselenazol-3(2H)-ones, with Ki value in a low picomolar range (<20 pM). The affinity was attributed to the increased π–π and π–cation interactions of the dihalogenated phenyl ring with αHis323 and αArg339 during the initial step of binding. Complementary biological studies with selected compounds on the inhibition of ureolysis in whole Proteus mirabilis cells showed a very good potency (IC50 < 25 nM in phosphate-buffered saline (PBS) buffer and IC90 < 50 nM in a urine model) for monosubstituted N-phenyl derivatives. The crystal structure of S. pasteurii urease inhibited by one of the most active analogs revealed the recurrent selenation of the Cys322 thiolate, yielding an unprecedented Cys322-S–Se–Se chemical moiety.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimized Ebselen-Based Inhibitors of Bacterial Ureases with Nontypical Mode of Action

et al. 2023

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“…180–181 °C, white or yellowish crystalline solid, soluble in DMSO, poorly soluble in water, Figure 1 ), an antioxidant, anti-inflammatory, antiatherosclerotic, and cytoprotective organoselenium compound [ 4 , 5 , 6 , 7 ] has recently become one of the leading compounds with repurposing potential. It shows antibiotic (but also antiviral, antifungal, and antiprotozoal) properties alone and in combination with existing drugs [ 4 , 5 , 6 , 7 , 8 , 9 ]. These properties are attributed to the multifaceted reactivity of ebselen with protein thiols.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of Ebselen

Maślanka

Mucha

2023

IJMS

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Ebselen is a low-molecular-weight organoselenium compound that has been broadly studied for its antioxidant, anti-inflammatory, and cytoprotective properties. These advantageous properties were initially associated with mimicking the activity of selenoprotein glutathione peroxidase, but the biomedical impact of this compound appear to be far more complex. Ebselen serves as a substrate or inhibitor with multiple protein/enzyme targets, whereas inhibition typically originates from the covalent modification of cysteine residues by opening the benzisoselenazolone ring and S–Se bond formation. The inhibition of enzymes of various classes and origins has been associated with substantial antimicrobial potential among other activities. In this contribution, we summarize the current state of the art regarding the antibacterial activity of ebselen. This activity, alone and in combination with commercial pharmaceuticals, against pathogens, including those resistant to drugs, is presented, together with the molecular mechanism behind the reactivity. The specific inactivation of thioredoxin reductase, bacterial toxins, and other resistance factors is considered to have certain therapeutic implications. Synergistic action and sensitization to common antibiotics assisted with the use of ebselen appear to be promising directions in the treatment of persistent infections.

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“…Ebselen (2-phenyl-1,2benzisoselenazol-3 [2H]-one) is a selenium-containing heterocytic cycle recognized to bound covalently to thiols to make seleno-disulfides responsible for its pharmacological impacts. Ebselen exhibits multipharmacological activities including impacts on apoptosis illness, cell differentiation, immune regulation, and neurodegenerative disease, with anti-bacterial, anti-fungal activity, detoxifying and anti-cancer activities [16]. Ebselen is a multifunctional component, so it is under clinical examinations and experimental investigations to elucidate its chemotherapeutic effect on several diseases as carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Modulatory impact of Ebselen against Diethylnitrosamine initiated Hepatocarcinogenesis in rats.

Arafa¹,

Kandil

Ibrahim

et al. 2023

Arab Journal of Nuclear Sciences and Applications

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Seleno-compounds have gained a significant consideration due to their efficiency as chemotherapeutic agents. The aim of the current work was to elucidate the impact of "Ebselen" on Diethylnitrosamine-initiated hepatocarcinogenesis in male albino rats. Hepatocellular carcinoma was initiated with oral supplementation of diethylnitrosamine (DEN] (15mg⁄ kg body-weight) for 2 months. Ebselen (5mg⁄ kg body-weight) was orally given to rats for 2 months after DEN-administration. Biochemical analysis includes assessment of liver functions (ALT&AST activities), kidney functions (urea and creatinine), determination of reduced glutathione (GSH) and malondialdehyde (MDA) contents in liver tissues [oxidative stress markers], alfa-fetoprotein (AFP) (tumor marker), besides Bcl2 expression and caspase-3 activities (apoptotic markers). The level of some essential trace elements (iron, zinc, copper, calcium and manganese) was also measured. The results revealed the powerful capacity of ebselen in minimizing the changes induced by DEN verified by significant increment in the level of hepatic antioxidant GSH accompanied by a marked decline in MDA concentration (marker of lipid peroxidation). Also, ebselen-treatment decreases ALT & AST activities, urea and creatinine concentrations. The increase of AFP, Bcl2 and the decrease of caspase-3 were less marked. The increase of Fe, Ca and Cu, the decrease of Zn and Mn were improved, compared to DEN-group. Histopathological examinations of hepatocyte cells were in accordance with the biochemical results confirming the potential role of ebselen in minimizing DNE-induced damage. Ebselen-treatment improved the harmful impacts initiated by DEN as it is an effective antioxidant and scavenger of free toxic radicals.

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

Cited by 12 publications

References 150 publications

Optimized Ebselen-Based Inhibitors of Bacterial Ureases with Nontypical Mode of Action

Optimized Ebselen-Based Inhibitors of Bacterial Ureases with Nontypical Mode of Action

Antibacterial Activity of Ebselen

Modulatory impact of Ebselen against Diethylnitrosamine initiated Hepatocarcinogenesis in rats.

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