BIOORGANIC CHEMISTRY
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2021
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IF 5.275
Le-Yun Sun,Cheng Chen,Jianpeng Su,Jia-Qi Li,Zhihui Jiang,Han Gao,Jia-Zhu Chigan,Huan-Huan Ding,Le Zhai,Ke-Wu Yang
The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised a global catastrophe. To date, there is no specific antiviral drug available to combat this virus, except the vaccine. In this study, the main protease (M pro ) required for SARS-CoV-2 viral replication was expressed and purified. Thirty-six compounds were tested as inhibitors of SARS-CoV-2 M pro by fluorescence resonance energy transfer (FRET) technique. The half-maximal inhibitory concentration (IC 50 ) values of Ebselen and Ebsulfur analogs were obtained to be in the range of 0.074–0.91 μM. Notably, the molecules containing furane substituent displayed higher inhibition against M pro , followed by Ebselen 1i (IC 50 = 0.074 μM) and Ebsulfur 2k (IC 50 = 0.11 μM). The action mechanism of 1i and 2k were characterized by enzyme kinetics, pre-incubation and jump dilution assays, as well as fluorescent labeling experiments, which suggested that both compounds covalently and irreversibly bind to M pro , while molecular docking suggested that 2k formed an S S bond with the Cys145 at the enzymatic active site. This study provides two very potent scaffolds Ebsulfur and Ebselen for the development of covalent inhibitors of M pro to combat COVID-19.
研究领域:
生物化学
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药理学
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病毒学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Xinyi Chen,Rui Wang,Yuhua Du,Yonghong Mou,Yan Gong,Xueyu Zhao,Wenzhong Li,Xin Li,Jin Wang,Yuancong Zhao
Atherosclerosis is often accompanied by inflammation and oxidative stress. Excessive reactive oxygen species (ROS) can damage the vascular endothelium, leading to endothelial dysfunction and reduced nitric oxide (NO) bioavailability. Further accumulation of ROS contributes to vascular cell damage, lipid peroxidation, and extracellular matrix deposition. Thus, clearing excess ROS and reshaping the oxidative microenvironment is essential for treating atherosclerosis (AS). In this study, Ebselen, which mimics glutathione peroxidase and possesses redox capabilities, was successfully synthesized. Subsequently, a multifunctional coating was designed using a combination of Ebselen and poly (trimethylene carbonate) (PTMC), capable of protecting cells from ROS-induced damage, promoting vascular endothelialization, and exhibiting anti-proliferative properties. The Ebselen-loaded coating effectively scavenges free radicals (with an elimination rate of 89 %), catalytically releases NO (0.96 × 10⁻¹⁰ to 1.26 × 10⁻¹⁰ mol/cm²/min), and sustainably delivers Ebselen to the lesion site through a redox cycle. Notably, this coating shows excellent hemocompatibility and cytocompatibility. Subcutaneous implantation results indicated that the fibrous capsule thickness of PTMC10 was the lowest, at just 47.7 % of that of PTMC. Therefore, the Ebselen-loaded coating presents promising applications in cardiovascular stents.
研究领域:
心血管医学
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材料科学
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生物医学工程
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PubMed
高影响因子
International Journal of Electrochemical Science
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2023
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IF 1.5
Qiongyu Zhang,Gang Liu,Lingbin Ou
This work reported an electrochemical method for the detection of SARS-CoV-2 major protease (Mpro). Specifically, ferrocene (Fc)-labeled peptide substrates were immobilized on the gold nanoparticles (AuNPs)-modified electrode. Cleavage of the peptides by Mpro led to the release of Fc tags and the decrease of the electrochemical signals. The analytical performance of the biosensor for analysis of Mpro was investigated. Inhibiting the activity of Mpro prevented the cleavage of the peptide substrates. The method was successfully used to evaluate the inhibition efficiency of a well-known inhibitor.
研究领域:
生物化学
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分析化学
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病毒学
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PubMed
高影响因子
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
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2018
·Vol. 16
·期 2
·115-122
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IF 1.593
Yanhong Jin,Di Li,Shiying Lu,Han Zhao,Zhao Chen,Wei Hou,Benfang Helen Ruan
Human glutamate dehydrogenase (GDH) plays an important role in neurological diseases, tumor metabolism, and hyperinsulinism–hyperammonemia syndrome (HHS). However, there are very few inhibitors known for human GDH. Recently, Ebselen was reported to crosslink with Escherichia coli GDH at the active site cysteine residue (Cys321), but the sequence alignment showed that the corresponding residue is Ala329 in human GDH. To investigate whether Ebselen could be an inhibitor for human GDH, we cloned and expressed an N-terminal His-tagged human GDH in E. coli. The recombinant human GDH enzyme showed expected properties such as adenosine diphosphate activation and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate dual recognition. Further, we developed a 2-(3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-tetrazol-3-ium-5-yl) benzenesulfonate sodium salt (EZMTT)-based assay for human GDH, which was highly sensitive and is suitable for high-throughput screening for potent GDH inhibitors. In addition, ForteBio binding assays demonstrated that Ebselen is a reversible active site inhibitor for human GDH. Since Ebselen is a multifunctional organoselenium compound in Phase III clinical trials for inflammation, an Ebselen-based GDH inhibitor might be valuable for future drug discovery for HHS patients.
研究领域:
生物化学
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药理学
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分子生物学
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医学
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PubMed
高影响因子
Biomaterials Science
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2024
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IF 5.8
Chang Liu,Linhua Li,Li Li,Qingyin Li,Jing Liu,Chunle Zhang,Zhengjiang Cao,Liang Ma,Xiaoxi Zeng,Ping Fu
Renal ischemia/reperfusion injury (RIRI) is an inevitable complication following kidney transplantation surgery, accompanied by the generation of massive of free radicals. The cascade of events including oxidative stress, extreme inflammation, cellular apoptosis, thrombosis disrupts the microenvironment of renal cells and the hematological system, ultimately leading to the development of acute kidney injury/ failure. Current research primarily focuses on reducing inflammation and mitigating damage to renal cells through antioxidative approaches. However, studies on simultaneously modulating the renal hematologic system remain unreported. Herein, a potent and novel drug-loaded nanomicelles can be efficiently self-assembled with magnolol (MG) and ebselen (EBS) by the π-π conjugation, hydrophobic action and the surfactant properties of Tween-80. The ultrasmall MG/EBS nanomicelles (Average particle size: 10–25 nm) not only fully preserve the activity of both drugs but also greatly enhance drug utilization (encapsulation rates: MG-90.1%, EBS-49.3%) and reduce drug toxicity. Furthermore, EBS, as a glutathione peroxidase mimic and NO catalyst, synergistically collaborates with the multifunctional MG to scavenge free radicals, significantly inhibiting inflammation and thrombosis while effectively preventing apoptosis of vascular endothelial cells and renal tubular epithelial cells. This study provides a new strategy and theoretical foundation for the simultaneous regulation of kidney cells and blood microenvironment stability.
研究领域:
药理学
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肾脏病学
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纳米医学
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DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
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2026
·
IF 3.5
Shuxiao Feng,Zongluo Zhang,Xuan Zhong,Jiahao Chen,Kejia Ren,Yishuai Wu,Tianxin Ji,Tong Wu,Shouren Zhang,Shiyong Xin
Ring-opened scaffolds from the benzisoselenazolone (BISZ) core offers a promising strategy for developing novel selenium-containing anticancer agents. • Novel 11 symmetric bis-open-ring ebselen analogues were synthesized, and 3d exhibited antiproliferative activity against seven human cancer cell lines, with IC₅₀ values ranging from 1.55 to 14.33 μM. Compound 3d also inhibited angiogenesis in transgenic zebrafish, reducing subintestinal vessel area by 25.6% and intersegmental vessel number by 15.8%. • Virtual screening and 100 ns molecular dynamics simulations revealed stable binding of 3d to human methionine aminopeptidase 2 (MetAP2), with a MM-GBSA binding free energy of −22.14 kcal/mol. • The dual inhibitory effects on cancer cell proliferation and angiogenesis suggest a promising mechanism for new ebselen open-ring analogue 3d as an anticancer agent. Optimizing ring-opened scaffolds from the benzisoselenazolone (BISZ) core offers a promising strategy for developing novel anticancer agents. Herein, eleven new ebselen analogues ( 3a–k ) featuring a symmetric bis-open-ring scaffold were synthesized and evaluated for in vitro antiproliferative activity against seven human cancer cell lines. Results shown compound 3d was the most potent across all seven tested panels, including lung carcinoma A549 (IC 50 = 3.75 μM), esophageal KYSE-30 (1.55 μM), hepatocellular HCCLM3 (5.57 μM), prostate PC3 (2.77 μM), colorectal HCT116 (14.12 μM), hepatocellular HepG2 (14.33 μM), and breast MDA-MB-231 (8.28 μM). At 6.25 μM, 3d significantly inhibited angiogenesis in transgenic zebrafish, reducing subintestinal vessel area by 25.6% ( p < 0.001) and intersegmental vessel number by 15.8% ( p < 0.01), suggesting a potential anti-angiogenic activity against cancer. Docking and MD simulations suggested a possible interaction of 3d to MetAP2. A novel ring-opened ebselen scaffold with potent anti-angiogenic activity against cancer: synthesis, biological evaluation, and molecular docking. Download: Download high-res image (118KB) Download: Download full-size image
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JOURNAL OF MOLECULAR STRUCTURE
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2021
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IF 3.196
Chenglu Zhang,Lu Zhang,Yuqing Li,Zhixuan Ren,Lu Li,Yanpeng Zhang,Yizheng Li,Cui Liu
A novel 1,8 - naphthalimide - ebselen fluorescent probe BPHN was synthesized. BPHN has great fluorescence properties: high quantum yield (0.5932), large Stokes shift (125 nm) and remarkable stability at wide pH range (5–11). The results of fluorescence spectroscopy experiments show that BPHN can recognize H 2 S selectively and sensitively. BPHN exhibits low LOD (0.129 μM) and fast response (90 s). The potential of BPHN as a biosensor for H 2 S was demonstrated by imaging of exogenous H 2 S in living cells. BPHN can also detect H 2 S qualitatively and quantitatively in actual water samples.
研究领域:
生物化学
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医学检测
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分析化学
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DOI
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2019
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IF 2.895
Yiming Li,Guanhui Chen,Yi He,Xiliu Zhang,Binghui Zeng,Chao Wang,Chen Yi,Dongsheng Yu
Background Patients with metabolic bone diseases often have high risk of titanium implant failure due to compromised bone regeneration ability. Clinical evidence indicates that the poor osteogenic ability is partly because of excessive oxidative stress. To date, specific treatments for these patients are urgently needed. Ebselen, a non-toxic organoselenium compound, is reported to be a potent antioxidant agent. In this study, we hypothesized that ebselen exerted protective effects on osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. Methods BMSCs were isolated from SD rats, and their morphology and multiple differentiation abilities were characterized. Proliferation rates of BMSCs treated with different concentrations of ebselen were analyzed. Then BMSCs were pretreated by hydrogen peroxide (H 2 O 2 ), after which ebselen at different concentrations (0, 1, 5, 10 μM) was added, alkaline phosphatase (ALP) activity, mineralization and osteogenic-related protein levels were evaluated and an optimum concentration of ebselen was selected. Subsequently, intracellular reactive oxygen species (ROS) generation and the role of the PI3K/AKT pathway were also investigated. Results Ebselen within a proper range could promote the proliferation of BMSCs. H 2 O 2 -induced oxidative stress suppressed osteogenic differentiation of BMSCs, which was verified by the decrease in ALP activity, calcium deposition, Runx2 and β-catenin expression. However, ebselen could alleviate osteogenic dysfunction of BMSCs. We also observed that ebselen reduced ROS accumulation in H 2 O 2 -pretreated BMSCs. Moreover, the pro-osteogenic effects afforded by ebselen were almost abolished by the Akt inhibitor. Conclusion We concluded that ebselen could attenuate osteogenic dysfunction of BMSCs induced by H 2 O 2 through an antioxidant effect and the activation of the PI3K/Akt pathway, suggesting that ebselen has a potential therapeutic effect for patients with metabolic bone diseases.
研究领域:
干细胞生物学
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骨科
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）