Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 11, 2023

Abstract Copper is a vital mineral, and an optimal amount of copper required to support normal physiologic processes in various systems, including the cardiovascular system. Over past few decades, copper-induced cell death, named cuproptosis, has become increasingly recognized as important process mediating pathogenesis progression disease (CVD), atherosclerosis, stroke, ischemia-reperfusion injury, heart failure. Therefore, in-depth understanding regulatory mechanisms cuproptosis CVD may be useful for improving management. Here, we review relationship between homeostasis cuproptosis-related pathways CVD, well therapeutic strategies addressing death CVD.

Language: Английский

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Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 16, 2023

Abstract Regulated cell death (RCD) is a regulable that involves well-organized signaling cascades and molecular mechanisms. RCD implicated in fundamental processes such as organ production tissue remodeling, removing superfluous structures or cells, regulating numbers. Previous studies have not been able to reveal the complete mechanisms, novel methods of are constantly being proposed. Two metal ions, iron (Fe) copper (Cu) essential factors leading RCDs only induce ferroptosis cuproptosis, respectively but also lead impairment eventually diverse death. This review summarizes direct indirect mechanisms by which Fe Cu impede growth various forms mediated these two metals. Moreover, we aimed delineate interrelationships between with distinct pathways shedding light on complex intricate govern cellular survival Finally, prospects outlined this suggest approach for investigating death, may involve integrating current therapeutic strategies offer promising solution overcome drug resistance certain diseases.

Language: Английский

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Smart composite antibacterial coatings with active corrosion protection of magnesium alloys

Journal of Magnesium and Alloys, Journal Year: 2022, Volume and Issue: 10(12), P. 3589 - 3611

Published: June 6, 2022

A new method of the formation composite coatings with function active corrosion protection magnesium alloys was developed using plasma electrolytic oxidation (PEO) method. Susceptibility PEO-layers to pitting evaluated localized electrochemical methods (SVET/SIET). The morphological features and properties were studied SEM/EDX, XRD, micro-Raman spectroscopy EIS/PDP measurements, respectively. effect surface layers impregnation inhibitor on their protective in a corrosive environment established. Additional achieved controllable coating pore sealing polymer. It found that polymer treatment PEO-layer does not reduce inhibitor's efficiency. formed inhibitor-and-polymer-containing decrease current density alloy 3 wt.% NaCl solution three orders magnitude. This predetermines prospect smart significantly expand field application electrochemically materials. mechanism degradation antibacterial activity inhibitor-containing against S. aureus methicillin-resistant strain proved vitro model. These are promising for reducing incidence implant-associated infections.

Language: Английский

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New anti-cancer explorations based on metal ions

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Oct. 23, 2022

Abstract Due to the urgent demand for more anti-cancer methods, new applications of metal ions in cancer have attracted increasing attention. Especially three kinds mode cell death, including ferroptosis, calcicoptosis, and cuproptosis, are great concern. Meanwhile, many been found induce death through different approaches, such as interfering with osmotic pressure, triggering biocatalysis, activating immune pathways, generating prooxidant effect. Therefore, varieties strategies based on above approaches studied applied applications. Moreover, contrast agents gradually become core components bioimaging technologies, MRI, CT, fluorescence imaging, which exhibit guiding significance diagnosis. Besides, nano-theranostic platforms experimentally shown efficient response endogenous exogenous stimuli, realizes simultaneous therapy diagnosis a controlled nano-system. However, most metal-based still early stages, clinical trials necessary confirm or not current expectations. This article will focus these explorations ions, hoping provide some theoretical support ideas.

Language: Английский

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Co‐based Nanozymatic Profiling: Advances Spanning Chemistry, Biomedical, and Environmental Sciences

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Sept. 19, 2023

Nanozymes, next-generation enzyme-mimicking nanomaterials, have entered an era of rational design; among them, Co-based nanozymes emerged as captivating players over times. been developed and garnered significant attention the past five years. Their extraordinary properties, including regulatable enzymatic activity, stability, multifunctionality stemming from magnetic photothermal conversion effects, cavitation relaxation efficiency, made a rising star. This review presents first comprehensive profiling in chemistry, biology, environmental sciences. The begins by scrutinizing various synthetic methods employed for nanozyme fabrication, such template sol-gel methods, highlighting their distinctive merits chemical standpoint. Furthermore, detailed exploration wide-ranging applications biosensing biomedical therapeutics, well contributions to monitoring remediation is provided. Notably, drawing inspiration state-of-the-art techniques omics, analysis undertaken, employing analogous statistical methodologies provide valuable guidance. To conclude, outlook on challenges prospects presented, spanning microscopic physicochemical mechanisms macroscopic clinical translational applications.

Language: Английский

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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(5), P. 2152 - 2175

Published: Jan. 19, 2023

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) monoamine oxidases (hMAO-A/B) for therapy neurodegenerative diseases. identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition hBChE (IC50 = 1.06 ± 0.31 nmol/L) hMAO-B 4.46 0.18 μmol/L). The crystal structures with provided structural basis binding, which was further studied by enzyme kinetics. Compound acted free radical scavenger biometal chelator, crossed blood-brain barrier, not cytotoxic, neuroprotective properties in 6-hydroxydopamine cell model Parkinson's disease. In addition, vivo studies anti-amnesic effect scopolamine-induced mouse AD without adverse effects on motoric function coordination. Importantly, chronic treatment double transgenic APPswe-PS1δE9 mice reduced amyloid plaque load hippocampus cortex female mice, underscoring disease-modifying 19.

Language: Английский

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Antioxidants in Anti-Alzheimer's Disease Drug Discovery

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 107, P. 102707 - 102707

Published: Feb. 27, 2025

Language: Английский

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Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure–Activity Relationships, and Perspectives

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 64(22), P. 16349 - 16379

Published: Nov. 15, 2021

The search for new antimicrobials is imperative due to the emergent resistance of microorganism strains. In this context, revisiting known classes like 8-hydroxyquinolines could be an interesting strategy discover agents. 8-hydroxyquinoline derivatives nitroxoline and clioquinol are used treat microbial infections; however, these drugs underused, being available in few countries or limited topical use. After years advances, last two decades, potent activity against several targets privileged structure nucleus have prompted increased interest design novel antimicrobial, anticancer, anti-Alzheimer agents based on class. Herein, we discuss current development antimicrobial structure-activity relationships class perspective using Furthermore, most investigated molecular concerning explored final section.

Language: Английский

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Structure–Activity Relationships of 8-Hydroxyquinoline-Derived Mannich Bases with Tertiary Amines Targeting Multidrug-Resistant Cancer

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(11), P. 7729 - 7745

Published: May 25, 2022

A recently proposed strategy to overcome multidrug resistance (MDR) in cancer is target the collateral sensitivity of otherwise resistant cells. We designed a library 120 compounds explore chemical space around previously identified 8-hydroxyquinoline-derived Mannich bases with robust MDR-selective toxicity. included study effect halogen and alkoxymethyl substitutions R5 combination different R7, shift base from R7 R5, as well introduction an aromatic moiety. Cytotoxicity tests performed on panel parental MDR cells highlight strong influence experimentally determined pKa values donor atom moieties, indicating that protonation metal chelation are important factors modulating anticancer activity studied compounds. Our results identify structural requirements increasing activity, providing guidelines for development more effective chelators targeting cancer.

Language: Английский

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Synthesis and anticancer mechanisms of zinc(ii)-8-hydroxyquinoline complexes with 1,10-phenanthroline ancillary ligands

Dalton Transactions, Journal Year: 2023, Volume and Issue: 52(15), P. 4737 - 4751

Published: Jan. 1, 2023

Twenty new zinc(II) complexes with 8-hydroxyquinoline (H-Q1-H-Q6) in the presence of 1,10-phenanthroline derivatives (D1-D10) were synthesized and formulated as [Zn(Q1)2(D1)] (DQ1), [Zn(Q2)2(D2)]·CH3OH (DQ2), [Zn(Q1)2(D3)] (DQ3), [Zn(Q1)2(D4)] (DQ4), [Zn(Q3)2(D5)] (DQ5), [Zn(Q3)2(D4)] (DQ6), [Zn(Q4)2(D5)]·CH3OH (DQ7), [Zn(Q4)2(D6)] (DQ8), [Zn(Q4)2(D3)]·CH3OH (DQ9), [Zn(Q4)2(D1)]·H2O (DQ10), [Zn(Q5)2(D4)] (DQ11), [Zn(Q6)2(D6)]·CH3OH (DQ12), [Zn(Q5)2(D2)]·5CH3OH·H2O (DQ13), [Zn(Q5)2(D7)]·CH3OH (DQ14), [Zn(Q5)2(D8)]·CH2Cl2 (DQ15), [Zn(Q5)2(D9)] (DQ16), [Zn(Q5)2(D1)] (DQ17), [Zn(Q5)2(D5)] (DQ18), [Zn(Q5)2(D10)]·CH2Cl2 (DQ19) [Zn(Q5)2(D3)] (DQ20). They characterized using multiple techniques. The cytotoxicity DQ1-DQ20 was screened human cisplatin-resistant SK-OV-3/DDP ovarian cancer (SK-OV-3CR) cells normal hepatocyte (HL-7702) cells. Complex DQ6 showed low IC50 values (2.25 ± 0.13 μM) on SK-OV-3CR cells, more than 3.0-8.0 times cytotoxic DQ1-DQ5 DQ7-DQ20 (≥6.78 μM), even 22.2 standard cisplatin, corresponding free H-Q1-H-Q6 D1-D10 alone (>50 μM). As a comparison, displayed nontoxic rates against healthy HL-7702 Furthermore, DQ11 induced significant apoptosis via mitophagy pathways. also significantly inhibited tumor growth an vivo SK-OV-3-xenograft model (ca. 49.7%). Thus, may serve lead complex for discovery antitumor agents.

Language: Английский

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