Copper Chelates Research Articles

BIOM-29. UNMASKING COPPER DEPENDENCE IN GLIOMA: 19-GENE SIGNATURE FOR PATIENT STRATIFICATION AND TARGETED THERAPY

Abstract Adult-type diffuse gliomas exhibit poor prognosis with limited treatment options. Although copper-targeted therapies have been previously explored in these tumors, they have yet to show significant benefits. To understand the role of copper in glioma biology we performed an in silico data analysis on the TCGA glioma cohorts to identify copper-homeostasis related genes (CHRG) with prognostic significance. This was done to enable patient stratification into appropriate treatment arms for future clinical trials involving copper targeted therapies. Furthermore, in vitro experimentation was performed to validate the functional outcomes observed from the in silico results. 19 CHRGs were identified to have prognostic association from the TCGA glioma cohorts. This gene signature regulates a broad range of cellular processes, including metal homeostasis, metabolism, extracellular matrix organization, and immune cell function. The CHRG signature enabled the development of a predictive model that allowed stratification of patients between high and low risk groups. In vitro spheroid growth assays in both U87 cell lines with or without IDH mutation elicited sustained growth inhibition after 6 days post treatment. Furthermore, copper chelation therapy modified the energy potential of these glioma cells in vitro leading to growth inhibition. This study established a predictive model using 19 CHRGs that enable patient stratification between high and low risk glioma patients. Furthermore, our in vitro experiments show the suitability of targeting intracellular copper to inhibit tumor growth. Further research is needed to understand the underlying mechanisms and explore optimal treatment combinations for improved outcomes. We aim to extend this approach to pediatric gliomas for improved risk assessment and personalized medicine.

Antioxidant activity, enzyme inhibition, photoprotection, cytotoxicity, and phytochemical profiling of sea lavender (Limonium algarvense Erben) seed extracts for dermo-cosmetic use

BackgroundDespite sea lavender being a medicinal species, research on its seeds’ biological properties and chemical composition is unexplored. Thus, this study evaluated the effect of different extraction solvents on the biological activities and chemical profile of greenhouse-cultivated sea lavender seeds, aiming at their potential use as a dermo-cosmetic ingredient. Therefore, ethyl acetate, acetone, ethanol, and water extracts were examined for their antioxidant activity, enzyme inhibition, photoprotection, and cytotoxicity, followed by phytochemical analysis through spectrophotometric methods, further detailed by Ultrahigh-Performance Liquid Chromatography Coupled with Electrospray Ionization Mass/Mass Spectrometry (UHPLC-Esi-MS/MS).ResultsThe water extract demonstrated significant antioxidant activity, evidenced by low half maximal effective concentration (EC50) values in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, reducing iron and chelating copper (296, 478, 230 and 678 µg/mL, respectively). The ethanol extract was more effective in inhibiting cosmetic-related enzymes, particularly elastase and hyaluronidase (2.18 and 3.21 µg/mL, respectively). The water and acetone extracts had the highest sun protection factors (23.2 and 18.9, respectively). All the extracts had nil to weak cytotoxicity (70–120% cell viability) towards mammalian cell lines. The water extract had the highest phenolics and condensed tannins (115 and 78.30 mg/g extract, respectively), while the ethanol contained the most flavonoids (62.73 mg/g extract). UHPLC-ESI–MS/MS analysis identified ethyl gallate, myricetin, rutin, and quercetin as major components of the ethanol extract, whereas myricetin-O-rutinoside isomers are predominant in the water extract.ConclusionsThese findings highlight the potential of greenhouse-cultivated sea lavender seeds as potential dermo-cosmetic ingredients, with ethanol and water extracts demonstrating superior biological activities and chemical profiles, significantly contributing to general skin health and protection.

L-Theanine Effectively Protects Against Copper-Facilitated Dopamine Oxidation: Implication for Relieving Dopamine Overflow-Associated Neurotoxicities.

Non-physiological disorders release dopamine into extracellular brain fluid to induce neurodegenerative brain diseases. The harmful mechanism of dopamine overflow is attributed to the dopamine-mediated production of hydroxyl radicals, suggesting that transition metal copper which is high in the brain is involved in promoting dopamine oxidation. MPP+ , an intermediate formed from the conversion of MPTP, is one of the most potent dopamine-releasing agents. It has been reported that L-theanine could improve motor dysfunction in MPTP-treated mice, suggesting that L-theanine may restrain copper-mediated oxidation of released dopamine. The present study examined the influences of L-theanine on extracellular dopamine-mediated cytotoxicity in the absence and presence of copper in SH-SY5Y cells. L-theanine significantly but only moderately suppressed cytotoxicity caused by dopamine alone. Surprisingly, dopamine together with copper rapidly and dramatically caused apoptotic responses by massively disrupting redox homeostasis. Nonetheless, L-theanine exhibited an extraordinary protective effect against these devastating events by chelating copper. The above great contrast in terms of copper could be recapitulated in a cell-free system. Though L-theanine reduced dopamine autoxidation as detected by HPLC, the capacity was not impressive, since a molar ratio of 10,000 (L-theanine to dopamine) was required for fully suppressing dopamine decrease. However, HPLC measurement showed that L-theanine was highly efficient in suppressing copper-mediated dopamine oxidation because only a molar ratio of 10 was required for fully suppressing dopamine decrease. Since copper plays a crucial role in promoting extracellular dopamine oxidation, our results suggest that L-theanine by chelating copper is an attractive food-based protective agent against dopamine overflow.

Additive Effects of Cu-ATSM and Radiation on Survival of Diffuse Intrinsic Pontine Glioma Cells.

Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive and treatment-resistant childhood primary brainstem tumors with a median survival of less than one year after diagnosis. The prevailing standard of care for DIPG, radiation therapy, does not prevent fatal disease progression, with most patients succumbing to this disease 3-8 months after completion of radiation therapy. This underscores the urgent need for novel combined-modality approaches for enhancing therapy responses. This study demonstrates that the cellular redox modulating drug, copper (II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) dose-dependently (1-3 μM) decreased clonogenic cell survival in SU-DIPG50 and SU-DIPG36 cell lines during 6 h of exposure but had no significant effect on survival in normal human astrocytes (NHA). Additional significant (>90%) decreases in DIPG clonogenic survival were observed at 24 h of Cu-ATSM exposure. However, NHAs also began to show dose-dependent 10-70% survival decreases at this point. Notably, 3 μM Cu-ATSM for 6 h resulted in additive clonogenic cell killing of DIPG lines when combined with radiation, which was not seen in NHAs and was partially inhibited by the copper chelator, bathocuproinedisulfonic acid. Cu-ATSM toxicity in DIPG cells was also inhibited by overexpression of mitochondrial-targeted catalase. These results support the hypothesis that Cu-ATSM is selectively cytotoxic to DIPGs by a mechanism involving H2O2 generation and copper and being additively cytotoxic with ionizing radiation.

Copper and Colorectal Cancer.

Minerals constitute only 5% of the typical human diet but are vital for health and functionality. Copper, a trace element, is absorbed by the human gut at 30-40% from diets typical of industrialized countries. The liver produces metallothioneins, which store copper. Copper is crucial for mitochondrial respiration, pigmentation, iron transport, antioxidant defense, hormone production, and extracellular matrix biosynthesis. Copper deficiency, often caused by mutations in the ATP7A gene, results in Menkes disease, an X-linked recessive disorder. On the contrary, Wilson disease is characterized by toxic copper accumulation. Cuproptosis, a unique form of cell death regulated by copper, is a subtype of necrosis induced by enhanced mitochondrial metabolism and intracellular copper accumulation. This process can reduce the malignant potential of tumor cells by inhibiting glucose metabolism. Therapeutically, copper and its complexes have shown efficacy in malignancy treatments. The disruption of copper homeostasis and excessive cuproplasia are significant in colorectal cancer development and metastasis. Therefore, manipulating copper status presents a potential therapeutic target for colorectal cancer, using copper chelators to inhibit copper formation or copper ion carriers to promote cuproptosis. This review highlights the role of copper in human physiology and pathology, emphasizing its impact on colorectal cancer and potential therapeutic strategies. Future AI-based approaches are anticipated to accelerate the development of new compounds targeting cuproptosis and copper disruption in colorectal cancer.

Polyvalent Aptamer Nanodrug Conjugates Enable Efficient Tumor Cuproptosis Therapy Through Copper Overload and Glutathione Depletion.

Cuproptosis, a recently identified form of copper-dependent cell death, shows promising tumor suppressive effects with minimal drug resistance. However, its therapeutic efficacy is hampered by its dependence on copper ions and the glutathione (GSH)-rich microenvironment in tumors. Here, we have developed polyvalent aptamer nanodrug conjugates (termed CuPEs@PApt) with a nucleosome-like structure to improve tumor cuproptosis therapy by exploiting mitochondrial copper overload and GSH depletion. Polyvalent aptamer (PApt), comprising polyvalent epithelial cell adhesion molecule aptamers for tumor targeting and repetitive PolyT sequences for copper chelation, facilitates efficient loading and targeted delivery of copper peroxide-Elesclomol nanodots (CuPEs). Upon internalization by tumor cells, Elesclomol released from CuPEs@PApt accumulates copper ions in mitochondria to initiate cuproptosis, while lysosomal degradation of CuP nanodots generates exogenous Cu2+ and H2O2, triggering a Fenton-like reaction for GSH depletion to enhance cuproptosis. In vitro and in vivo experiments confirm the efficacy of this strategy in inducing tumor cell cuproptosis and immunogenic cell death, the latter contributing to the activation of the antitumor immune response for synergistic tumor growth inhibition.

Catalytic Activation of Thioglycosides with Copper-Carbenes for Stereoselective 1,2-Cis-Furanosylations.

Thioglycoside activation, crucial for oligosaccharide synthesis, faces challenges with the need for stoichiometric promoters, additives, and cryogenic conditions, particularly in stereoselective 1,2-cis-linkage formation. This study introduces a carbene-based catalytic method using Cu(OTf)2 for thioglycoside activation, enabling efficient 1,2-cis-furanosylation in ribose and arabinose. The method is orthogonal to conventional thioglycoside and alkyne donors, accommodates sterically demanding acceptors, and achieves stereoselectivity independent of the donor anomeric configuration and C2-protecting groups, with copper chelation playing a key role.

Effects of fig and pineapple powder on metabolite compounds and health-promoting properties in fermented goat meat sausage.

The objective of this research was to identify the metabolite compounds and health-promoting properties of goat meat fermented sausages containing different amounts of fig and pineapple powder (0.1%, 0.25%, and 0.5%), which are presented by F1, F2, F3 and P1, P2, P3, separately. Fermented sausages were manufactured from the lean meat of female goats. The samples extracted from the goat meat fermented sausages were evaluated for their metabolite compounds, antioxidants, and angiotensin-converting enzyme inhibitory activity. The results showed that the diphenyl picrylhydrazyl radical scavenging activity, azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, and angiotensin-converting enzyme inhibitory activity were the highest in F3 (p<0.05), whereas the hydroxyl radical (°OH) scavenging capacity was the highest in P3 (p<0.05). In addition, F3 and F2 showed the highest superoxide anion radical scavenging activity (p<0.05), whereas F3 and P3 showed the highest copper chelating activity (p<0.05). Based on the metabolite compounds, hydrophobic amino acids, aromatic amino acids, and bitter amino acids were abundant in F3. Both F3 and P3 contained high concentrations of umami-producing compounds. The incorporation of 0.5% fig powder into goat meat fermented sausage showed improved biological activities based on metabolite compounds.

The effect of the composition of hepatoprotective action on biochemical and morphostructural changes in the body of laying hens under thermal stress

To reduce the negative effects of hyperthermia on the body of farm animals and poultry, various drugs and feed additives are currently used. Which do not have sufficiently adaptogenic and antitoxic properties. We studied the effect of a hepatoprotective composition consisting of dried live yeast, amorphous silicon dioxide, propylene glycol, calcium propionate, ascorbic acid, manganese, copper and zinc chelates, methionine and choline chloride on the variability of biochemical and morphological parameters of the body of laying hens under temperature stress. It was simulated by increasing the air temperature in a building where laying hens were kept from 18.0 ± 1.0 °C to 28.0 ± 1.0 °C for 48 hours. Due to hyperthermia, changes in biochemical and morphofunctional parameters were observed in the tissues and organs of birds. The obtained values of the biochemical parameters of blood serum in the birds of the control group indicated the intensity of the adaptive capabilities of their body. A complex of morphological changes confirmed a violation of protein metabolism and the regenerative-compensatory process. Pathological changes in the structure of the duodenum, characteristic of catarrhal-necrotic duodenitis, were identified. The stress reaction was also reflected in the condition of the heart muscle, in which an inflammatory process developed against the background of granular dystrophy of cardiomyocytes. The results of biochemical studies of blood serum in birds of the experimental group indicated an increase in the anti-stress response to a temperature stimulus under the influence of the studied composition (tendency to increase glucose and calcium, increase alkaline phosphatase activity by 47.4 %). The introduction of a hepatoprotective composition into the diet of laying hens during periods of temperature stress did not lead to disruption of the structure of tissues and organs, preserving cellular metabolic mechanisms. The

Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review.

Trientine tetrahydrochloride (TETA-4HCl, Cuvrior®) is a copper chelating agent with the active moiety triethylenetetramine (trientine), developed by Orphalan, Inc. to address the unmet needs in the treatment of Wilson disease. The journey from bench to bedside builds upon the documented safety profile of trientine hydrochloride capsules developed initially to meet the needs of individuals intolerant to D-penicillamine (DPA). Trientine hydrochloride capsules are inherently unstable requiring strict cold chain storage conditions from production, transportation, and use at home by the patient. Trientine tetrahydrochloride has a distinctive, patent-protected unique polymorphic form, which permits the production at scale of film-coated scored tablets deemed room temperature stable for 36 months. Trientine tetrahydrochloride is supported by a well-characterized pharmacodynamic, pharmacokinetic, and metabolic profile demonstrating reliable and predictable dose linearity and dose proportionality kinetics. Trientine tetrahydrochloride is the only trientine formulation that has been compared with DPA in a prospective randomized clinical trial, demonstrating non-inferiority to DPA in adults with stable Wilson disease. On 28 April, 2022, the US Food and Drug Administration approved TETA-4HCl for use in adult patients with Wilson disease who are de-coppered and tolerant to DPA. Health authorities in multiple countries worldwide have approved TETA-4HCl for the treatment of adults and children aged 5 years or more who are intolerant to DPA including the European Union, UK, Saudi Arabia, Switzerland, Colombia, Australia, New Zealand, and China. This article aims to provide a comprehensive narrative review of the key milestones in the development of TETA-4HCl.

Bifunctional Copper Chelators Capable of Reducing Aβ Aggregation and Aβ-Induced Oxidative Stress.

Five bifunctional copper chelating agents, Alz-(1-5), designed to prevent beta-amyloid (Aβ) aggregation, were synthesized, and the leader compound (Alz-5) was chosen. Alz-5 acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity. Reactive oxygen species measurements provided by the Pt-nanoelectrode technique in single Aβ42-affected human neuroblastoma SH-SY5Y cells revealed significant antioxidant activity of Alz-5. AFM data obtained on Aβ42 fibrils clearly indicate the antiaggregating property of Alz-5. To gain insights into the changes in the physiomechanical properties of Aβ42-affected cells, as well as in order to evaluate the antiaggregating ability of Alz-5, Young's modulus mapping on living SH-SY5Y cells affected consequently by Aβ42 and Alz-5 was conducted, and the ability of Alz-5 to decrease cell rigidity induced by Aβ42 was indisputably proven. Low cell toxicity and antioxidating properties, in conjunction with AFM and SICM-based biophysical provided on Aβ42-affected SH-SY5Y cells, support Alz-5 as a potential inhibitor of Aβ aggregation.

Design, Synthesis, and Anti-Melanogenic Activity of 2-Mercaptomethylbenzo[d]imidazole Derivatives Serving as Tyrosinase Inhibitors: An In Silico, In Vitro, and In Vivo Exploration.

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using the copper chelator pyrocatechol violet and assays measuring TYR activity in the presence or absence of exogenous CuSO4. The inhibition mechanisms of derivatives 1, 3, 8, and 9, which showed excellent TYR inhibitory activity, were elucidated through kinetic studies and supported by the docking simulation results. Derivatives 3, 7, 8, and 10 significantly inhibited cellular TYR activity and melanin production in B16F10 cells in a dose-dependent manner, with stronger potency than kojic acid. Furthermore, in situ, derivatives 7 and 10 showed stronger inhibitory effects on B16F10 cell TYR activity than kojic acid. Six derivatives, including 8, showed highly potent depigmentation in zebrafish larvae, outpacing kojic acid even at 200-670 times lower concentrations. Additionally, all derivatives could scavenge for reactive oxygen species without causing cytotoxicity in epidermal cells. These results suggested that 2-MMBI derivatives are promising anti-melanogenic agents.

Copper-Consuming Nanoplatform for Alleviating Hypoxia and Overcoming Resistance to Sonodynamic Therapy of Breast Cancer.

Sonodynamic therapy (SDT) is a promising treatment modality for breast cancer; however, its effectiveness is often impeded by the hypoxic tumor microenvironment owing to an insufficient oxygen supply in the solid tumors. To overcome this challenge, we elaborately developed a 4T1 tumor-targeted multifunctional nanoagent by integrating both dendrimer-structured copper chelating agents and organic sonosensitizers (IR820) into a biotin-modified nanoliposome via a microfluidic-assisted self-assembly. In particular, the aforementioned copper chelating agent was constructed by introducing multiple xanthate groups into a dendrimer polymer, which showed a significant selectivity for the consumption of the intracellular copper levels. Based on this, the nanoliposome-based therapeutic not only disrupted the activity of the mitochondrial complex IV to directly inhibit the tumor cell proliferation but also suppressed the resistance to the SDT via inhibition of the oxygen consumption for cellular respiration. Both in vitro and in vivo studies confirmed that the designed nanoagents exhibit a synergistic tumor inhibition effect of copper consumption and IR820-mediated SDT. Taken together, this approach establishes a proof-of-concept for the construction of a copper-ion-modulated nanomedicine to significantly enhance the efficiency of oxygen-dependent cancer treatments.

Synthesis, Copper Chelation, and Free Radical Scavenging Ability of Edaravone: An Undergraduate Medicinal Chemistry Laboratory Experiment

Synthesis, Copper Chelation, and Free Radical Scavenging Ability of Edaravone: An Undergraduate Medicinal Chemistry Laboratory Experiment

Sirtuin 7 ameliorates cuproptosis, myocardial remodeling and heart dysfunction in hypertension through the modulation of YAP/ATP7A signaling.

Myocardial fibrosis is a typical pathological manifestation of hypertension. However, the exact role of sirtuin 7 (SIRT7) in myocardial remodeling remains largely unclear. Here, spontaneously hypertensive rats (SHRs) and angiotensin (Ang) II-induced hypertensive mice were pretreated with recombinant adeno-associated virus (rAAV)-SIRT7, copper chelator tetrathiomolybdate (TTM) or copper ionophore elesclomol, respectively. Compared with normotensive controls, reduced SIRT7 expression and augmented cuproptosis were observed in hearts of hypertensive rats and mice with decreased FDX1 levels and increased HSP70 levels. Notably, intervention with rAAV-SIRT7 and TTM strikingly prevented DLAT oligomers aggregation, and elevated ATP7A and TOM20 expressions, contributing to the alleviation of cuproptosis, mitochondrial injury, myocardial remodeling and heart dysfunction in spontaneously hypertensive rats and Ang II-induced hypertensive mice. In cultured rat primary cardiac fibroblasts (CFs), rhSIRT7 alleviated CuCl2, Ang II or elesclomol-induced cuproptosis and fibroblast activation by blunting DLAT oligomers accumulation and downregulating α-SMA expression. Additionally, conditioned medium from rhSIRT7-pretreated CFs remarkably mitigated cellular hypertrophy and mitochondrial impairments of neonatal rat cardiomyocytes, as well as cell migration and polarization of RAW 264.7 macrophages. Importantly, verteporfin reduced CuCl2-induced cuproptosis, mitochondrial injury and fibrotic activation in CFs. Knockdown of ATP7A with si-ATP7A blocked cellular protective effects of rhSIRT7 and verteporfin in CFs. In conclusion, SIRT7 attenuates cuproptosis, myocardial fibrosis and heart dysfunction in hypertension through the modulation of YAP/ATP7A signaling. Targeting SIRT7 is of vital importance for developing therapeutic strategies in hypertension and hypertensive heart disorders.

Phytochemical Profiles and Biological Activities of Five Wild Camellia Species from Ta Dung, Vietnam.

The C. luuana Orel & Curry (TD3), C. furfuracea (Merr.) Cohen-Stuard (TD4), C. bidoupensis Truong, Luong & Tran (TD6), C. sinensis (L.) Kuntze (TD7), and C. kissii var. spp (TD8), have been traditionally used as a health-promoting beverage by local people in Ta Dung, Dak Nong. Despite their potential health benefits, further scientific data on biological and phytochemical properties of these plants is needed. To address this issue, this study was conducted to investigate phytochemical and biological properties of five Camellia species extracts, using DPPH, ABTS radical scavenging, copper chelating (Cu-chelator), and tyrosinase inhibition (TI), α-amylase (Al-AI), and α-glucosidase (Al-GI) analyses. As results, ten compounds were identified using UPLC method, in which catechins (mainly EGCG and catechin (Cat)), were the most prevalent, and followed by chlorogenic acid (ChlA), quercitrin (Querci), rutin, and quercetin (Querce). Additionally, multiple factor analysis (MFA) also revealed that TD7, TD3, and TD4 containing high TPC, TFC, high concentrations of EGCG, ChlA, and caffeine were responsible for their high DPPH, ABTS radical scavenging activities, as well asTI, Al-AI and Al-GI. Furthemore, TD6 and TD8, possessing elevated levels of Apig, Querci, Rutin, Querce, Cat, and EA, exhibited a high Cu-chelator property, but a weak enzyme inhibition. From all above-mentioned results, the antioxidative and enzyme inhibitory potentials of Camellia species extracts collected in Dak Nong province in Vietnam were scientifically demonstrated paving a pathway to develop health supplement in further studies.

Review to Elucidate the Correlation between Cuproptosis-Related Genes and Immune Infiltration for Enhancing the Detection and Treatment of Cervical Cancer.

Copper is a vital trace element in oxidized and reduced forms. It plays crucial roles in numerous biological events such as redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy, and immune modulation. Maintaining the balance of copper in the body is essential because its deficiency and excess can be harmful. Abnormal copper metabolism has a two-fold impact on the development of tumors and cancer treatment. Cuproptosis is a form of cell death that occurs when there is excessive copper in the body, leading to proteotoxic stress and the activation of a specific pathway in the mitochondria. Research has been conducted on the advantageous role of copper ionophores and chelators in cancer management. This review presents recent progress in understanding copper metabolism, cuproptosis, and the molecular mechanisms involved in using copper for targeted therapy in cervical cancer. Integrating trace metals and minerals into nanoparticulate systems is a promising approach for controlling invasive tumors. Therefore, we have also included a concise overview of copper nanoformulations targeting cervical cancer cells. This review offers comprehensive insights into the correlation between cuproptosis-related genes and immune infiltration, as well as the prognosis of cervical cancer. These findings can be valuable for developing advanced clinical tools to enhance the detection and treatment of cervical cancer.

Copper ions: The invisible killer of cardiovascular disease (Review).

Copper, a vital trace element, is indispensable for the maintenance of physiological functioning, particularly in the cardiac system. Unlike other forms of cell death such as iron death and apoptosis, copper‑induced cell death has gained increasing recognition as a significant process influencing the development of cardiovascular diseases. The present review highlights the significance of maintaining copper homeostasis in addressing cardiovascular diseases. This review delves into the crucial roles of copper in physiology, including the metabolic pathways and its absorption, transport and excretion. It provides detailed insights into the mechanisms underlying cardiovascular diseases resulting from both excess and deficient copper levels. Additionally, it summarizes strategies for treating copper imbalances through approaches such as copper chelators and ion carriers while discussing their limitations and future prospects.

Synthesis, Structural Characterization, Anticancer, Antimicrobial, Antioxidant, and Computational Assessments of Zinc(II), Iron(II), and Copper(II) Chelates Derived From Selenated Schiff Base

ABSTRACTNovel selenated azomethine ligand (MSeOH) and its Zn(II), Fe(II), and Cu(II) chelates were synthesized. Their chemical structures were confirmed by molar conductivity, thermal analysis, X‐ray diffraction, IR, NMR, and MS spectroscopic techniques. The antitumor and antimicrobial properties were evaluated against various mammalian cells and pathogenic strains. Furthermore, the antioxidant activities were also assessed using DPPH and SOD bioassays. To gain a deeper understanding of the molecular structure and electronic properties of these complexes, a density functional theory (DFT) study was conducted. The parameters examined in this study provide valuable insight into the bonding, electronic properties, reactivity, and polarity of the compounds under investigation. The biological and theoretical results point to promising activities of the selenated ligand and its complexes.

The Effect of Trientine on AlCl3-Induced Cognitive Dysfunction and Biochemical Changes in the Hippocampus of Rats.

Cognitive impairments affect millions of people worldwide with an increasing prevalence. Research on their etiology and treatment is developing, nevertheless significant gaps remain. Trientine (TETA), as a copper chelator, has been shown to have beneficial effects in different human chronic diseases such as diabetic cardiomyopathy and neuropathy. Here, we examined the impact of TETA on AlCl3-induced neurocognitive dysfunctions and molecular changes in the hippocampus of rats.Thirty-six male Wistar rats (weighing 200-250 g) were randomly divided into four groups including control, TETA (100 mg/kg/day), AlCl3 (100 mg/kg/day), and AlCl3 (100 mg/kg/day)+TETA (100 mg/kg/day), and received chemicals by gavage for 30 days. At the end of the treatment, the open field maze, elevated plus maze, novel object recognition memory test, and shuttle box test were done. Then after, brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 β (GSK-3β), acetylcholinesterase activity, oxidative stress markers, and inflammatory mediators were measured in the hippocampus.AlCl3 increased anxiety-like behaviors and impaired recognition and short-term memory. TETA was able to improve AlCl3-induced anxiety-like behaviors and short-term memory dysfunction. In the AlCl3-treated group, there was a significant increase in GSK-3β, oxidative stress, pro-inflammatory and pro-apoptotic markers, and decreased BDNF in the hippocampus. Co-administration of TETA was able to decrease lipid peroxidation, inflammation, GSK-3β, and acetylcholinesterase activity, and increase BDNF in the hippocampus compared with AlCl3-treated rats.It can be concluded that TETA was able to improve neurobehavioral and neurocognitive functions by alleviating oxidative stress, inflammation, and pro-apoptotic pathways leading to the normalization of BDNF and GSK-3β.