Sara La Manna , Valeria Panzetta , Sossio Fabio Graziano , Irene Cipollone , Iogann Tolbatov , Alessandro Marrone , Maria Monti , Paolo Antonio Netti , Antonello Merlino , Konrad Kowalski , Daniela Marasco
{"title":"Heterobimetallic ferrocenyl-chromone compounds as selective inhibitors of amyloid aggregation","authors":"Sara La Manna , Valeria Panzetta , Sossio Fabio Graziano , Irene Cipollone , Iogann Tolbatov , Alessandro Marrone , Maria Monti , Paolo Antonio Netti , Antonello Merlino , Konrad Kowalski , Daniela Marasco","doi":"10.1016/j.jinorgbio.2025.112932","DOIUrl":"10.1016/j.jinorgbio.2025.112932","url":null,"abstract":"<div><div>Amyloid aggregation is a key process in neurodegeneration, producing toxic species that contribute to disease progression. This underscores the urgent need to identify novel agents capable of reducing toxicity by modulating this aggregation process. Two heterobimetallic complexes incorporating a ferrocenyl-chromone (Fc-Chr) core were investigated: one featuring an additional gold(I) triphenylphosphine moiety, Fc-Chr-AuP(Ph)₃, and the other containing a dicobalt hexacarbonyl-alkyne unit, Fc-Chr-Co₂(CO)₆.</div><div>Their effects were evaluated toward on the aggregation of two amyloid models: the peptide spanning residues 264–277 of nucleophosmin 1 (NPM1<sub>264</sub><sub>–</sub><sub>277</sub>) and the C-terminal fragment of the amyloid-β peptide (Aβ<sub>21</sub><sub>–</sub><sub>40</sub>) each with unique primary sequences, self-aggregation mechanisms and kinetics. Thioflavin T- assays allowed to assess the impact of the metal complexes on the aggregation of two amyloids. Results indicate that the two complexes inhibit the early stages of the aggregation of peptides in a dose-dependent manner and a greater effect on NPM1<sub>264</sub><sub>–</sub><sub>277</sub> when compared to Aβ<sub>21</sub><sub>–</sub><sub>40</sub> was observed. Native electrospray ionization mass spectrometry revealed the formation of peculiar metal/peptide adducts in dependence on different metal-units in the complexes. Scanning electron microscopy (SEM) and density function theory (DFT) were also employed to further characterize the interaction between the metal compounds and the investigated peptides, while preliminary cell viability assays in SH-SY5Y cells supported inhibitory effects on the aggregation and showed reduction of amyloid cytotoxicity. Fc-Chr-Co₂(CO)₆ demonstrated the highest efficacy in modulating peptide aggregation, exerting a more significant impact on NMP1<sub>264</sub><sub>–</sub><sub>277</sub> relative to Aβ₂₁₋₄₀. These results support the use of ferrocenyl-chromone containing metal complexes as modulators of amyloid peptide aggregation.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112932"},"PeriodicalIF":3.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A 4-phenylbutyric acid-conjugated platinum diimine complex: Photocytotoxicity, cell cycle arrest and apoptosis in vitro","authors":"Xuemei Guo, Yuxin Lu, Xu Zhang, Xin Wang, Hongfei Wang, Zhigang Zhang","doi":"10.1016/j.jinorgbio.2025.112930","DOIUrl":"10.1016/j.jinorgbio.2025.112930","url":null,"abstract":"<div><div>4-phenylbutyric acid (PBA) is a class <strong>I</strong> and <strong>II</strong> histone deacetylase inhibitor, which can decrease cell proliferation, enhance cell differentiation, and induce apoptosis and cell cycle arrest in various cancer cells. PBA-modified photoactive platinum diimine complex has been prepared and characterized to augment its photodynamic therapy efficacy. Its ability to generate singlet oxygen, behavior in the presence of esterase, photocytotoxicity, cell cycle distribution, and apoptosis-inducing ability in MCF-7 cells have also been studied. The results suggested that the PBA-modified platinum diimine complex could act as a good singlet oxygen producer, release PBA in the presence of esterase, induce potent photocytotoxicity in tumor cells with a IC<sub>50</sub> value of 3.67 ± 0.67 μM, arrest cell cycle at S phase, and induce cell death <em>via</em> apoptosis with the percentage of total apoptotic cells being 34.65 %. The results also revealed that PBA might be able to modulate the mode of cell cycle arrest induced by the photosensitizer in tumor cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112930"},"PeriodicalIF":3.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chelsey R. Fontenot , Thomas Hoepner , Jin Xiong , Huangen Ding , Codrina V. Popescu
{"title":"Mössbauer studies of the redox state of the ferric uptake regulator [2Fe–2S]2+ cluster in Escherichia coli","authors":"Chelsey R. Fontenot , Thomas Hoepner , Jin Xiong , Huangen Ding , Codrina V. Popescu","doi":"10.1016/j.jinorgbio.2025.112928","DOIUrl":"10.1016/j.jinorgbio.2025.112928","url":null,"abstract":"<div><div>The Ferric uptake regulator (Fur) proteins from <em>Haemophilus influenzae</em> and <em>Escherichia coli</em> overexpressed in <em>E. coli</em> cells (MC4100) grown in M9 medium supplemented with <sup>57</sup>Fe were studied with Mössbauer spectroscopy. Previous studies have shown that Fur proteins from <em>H. influenzae</em> and <em>E. coli</em> bind a [2Fe–2S]<sup>2+</sup> cluster in response to elevation of intracellular free iron content. Here we find that when the [2Fe–2S]<sup>2+</sup> clusters in purified Fur proteins are reduced with dithionite, the reduced clusters are quickly decomposed, forming compounds with two distinct spectral signatures of high spin Fe(II) in tetrahedral and octahedral coordination, respectively. The instability of the reduced [2Fe-2S]<sup>1+</sup> cluster in Fur is unique, as the [2Fe–2S]<sup>2+</sup> clusters in many other proteins can reversibly undergo one-electron reduction-oxidation. The Mössbauer spectra of whole <em>E. coli</em> cells overexpressing Fur proteins show a quadrupole doublet with the isomer shift of δ<sub>1</sub> = 0.28 mm/s and ΔE<sub>Q1</sub> = 0.52 mm/s, typical for oxidized [2Fe-2S]<sup>2+</sup> clusters and identical with that in the purified Fur protein. The corresponding spectra in large applied magnetic fields show the diamagnetic pattern that unambiguously reveals an exchange-coupled system with a diamagnetic electronic ground state, which confirms its assignment to the oxidized [2Fe-2S]<sup>2+</sup> cluster clusters from Fur. No reduced [2Fe-2S]<sup>1+</sup> clusters of Fur are observed in the whole-cell <em>E. coli</em> spectra. The Mössbauer spectra of the whole-cell <em>E. coli</em> without the Fur expression do not contain the components associated with the [2Fe–2S]<sup>2+</sup> cluster of Fur.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112928"},"PeriodicalIF":3.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rukmal Karunaratne , Erik P. Willems , Oliver Zerbe , Eva Freisinger
{"title":"Elucidating the metalation pathway of the Ec-1 metallothionein βE-domain: Insights into ZnII binding and protein folding","authors":"Rukmal Karunaratne , Erik P. Willems , Oliver Zerbe , Eva Freisinger","doi":"10.1016/j.jinorgbio.2025.112931","DOIUrl":"10.1016/j.jinorgbio.2025.112931","url":null,"abstract":"<div><div>Metallothioneins (MTs) are small cysteine-rich proteins that preferentially bind d<sup>10</sup> metal ions such as Zn<sup>II</sup>, Cu<sup>I</sup>, and Cd<sup>II</sup>, playing essential roles in metal ion homeostasis and detoxification. The E<sub>c</sub>-1 metallothionein from <em>Triticum aestivum</em> (common bread wheat) was the first plant metallothionein for which a 3D structure was successfully determined, although this structure represents only the fully metalated state of the protein. In this study, we aim to elucidate the metalation pathway of the β<sub>E</sub>-domain of wheat E<sub>c</sub>-1. This domain features a mononuclear Zn<sup>II</sup> binding site composed of two cysteine and two highly conserved histidine residues, reminiscent of the Zn-finger motifs found in certain proteins. Moreover, the domain forms a trinuclear Zn<sub>3</sub>Cys<sub>9</sub> cluster, similar to the β-cluster motif observed, for example, in vertebrate MTs. To investigate the metalation pathway of the β<sub>E</sub>-domain, we combined nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and targeted cysteine modification techniques. Our results confidently identify the sequential binding site regions for each of the four Zn<sup>II</sup> ions and reveal intriguing, unexpected insights into the folding pathway of the peptide backbone.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112931"},"PeriodicalIF":3.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mia M. Biernat , Olivia G. Camp , Daniel N. Moussa , Awoniyi O. Awonuga , Husam M. Abu-Soud
{"title":"The interplay between the myeloperoxidase-hypochlorous acid system, heme oxygenase, and free iron in inflammatory diseases","authors":"Mia M. Biernat , Olivia G. Camp , Daniel N. Moussa , Awoniyi O. Awonuga , Husam M. Abu-Soud","doi":"10.1016/j.jinorgbio.2025.112927","DOIUrl":"10.1016/j.jinorgbio.2025.112927","url":null,"abstract":"<div><div>Accumulated unbound free iron (Fe(II or III)) is a redox engine generating reactive oxygen species (ROS) that promote oxidative stress and inflammation. Iron is implicated in diseases with free radical pathology including cardiovascular, neurodegenerative, reproductive disorders, and some types of cancer. While many studies focus on iron overload disorders, few explore the potential link between the myeloperoxidase-hypochlorous acid (MPO-HOCl) system and localized iron accumulation through heme and iron‑sulfur (Fe<img>S) cluster protein destruction. Although inducible heme oxygenase (HO-1), the rate-limiting enzyme in heme catabolism, is frequently associated with these diseases, we hypothesize that HOCl also contributes to the generation of free iron and heme degradation products. Furthermore, HO-1 and HOCl may play a dual role in free iron accumulation by regulating the activity of key iron metabolism proteins. Enzymatic and non-enzymatic modulators, as well as scavengers of HOCl, can help prevent heme destruction and reduce the accumulation of free iron. Given iron's role in disease progression and severity, identifying the primary sources, mechanisms, and mediators involved in free iron generation is crucial for developing effective pharmacological treatments. Further investigation focusing on the specific contributions of the MPO-HOCl system and free iron is necessary to explore novel strategies to mitigate its harmful effects in biological systems.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112927"},"PeriodicalIF":3.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interaction of half-sandwich Rh(III) ion and some of its complexes with endogenous imidazole derivatives","authors":"Azza A. Hassoon , Attila Szorcsik , Tamás Gajda","doi":"10.1016/j.jinorgbio.2025.112913","DOIUrl":"10.1016/j.jinorgbio.2025.112913","url":null,"abstract":"<div><div>An increasing number of {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup> complexes are reported to possess promising medical, mostly anticancer activities. In parallel, growing interest has also focused on the interactions between {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup>-based metallodrugs and macromolecular components of biological fluids, since the biospeciation of these potential metallodrugs may strongly influence their overall pharmacological properties. Less attention was paid to the interaction of {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup> complexes with low molecular mass (LMM) constituents of biological fluids, which may also have significant impact on their biospeciation. From this point of view, the biogenic imidazole derivatives are the most important, since the primary binding sites of proteins for {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup> cation are the surface histidine groups. Several imidazole containing endogenous LMM components are known, which have relevant concentrations in certain biological fluids, such as plasma. Therefore, here we report systematic solution thermodynamic and solution structural (potentiometric, UV–Vis, ESI-MS and <sup>1</sup>H NMR) study on the interaction of {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup> cation with thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH<sub>2</sub>, <strong>L</strong><sup><strong>1</strong></sup>), carnosine (β-alanyl-histidine, <strong>L</strong><sup><strong>2</strong></sup>), carcinine (β-alanyl-histamine, <strong>L</strong><sup><strong>3</strong></sup>), histidine (<strong>L</strong><sup><strong>4</strong></sup>) and the human growth modulator tripeptide GHK (Gly-His-Lys, <strong>L</strong><sup><strong>5</strong></sup>). The results indicate, that these biogenic ligands, especially histidine and GHK, possess very high binding ability towards {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup> cation, higher than for the well-known histidine-peptide binder copper(II). In addition, we also studied the interaction of two simple [Rh(η<sup>5</sup>-Cp*)(A)Cl]<sup>+</sup> complexes (where A = 2,2′-bipyridyl (<strong>bpy</strong>) or ethylenediamine (<strong>en</strong>)), as mimics of potentially anticancer compounds, with the above listed endogenous imidazole derivatives. Beside the formation of ternary [Rh(η<sup>5</sup>-Cp*)(A)(L)] complexes, histidine and GHK, having exceptionally high {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup> binding ability, are also able to displace <strong>en</strong> or <strong>bpy</strong> from the coordination sphere of Rh(III). Moreover, histidine and GHK successfully compete even with human serum albumin under near physiological conditions, and thus may have fundamental effect on the blood transport and biodistribution of any {Rh(η<sup>5</sup>-Cp*)}<sup>2+</sup>-based bioactive compounds.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112913"},"PeriodicalIF":3.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jorge Melones-Herrero , Francisco Aguilar-Rico , Ana I. Matesanz , Carmela Calés , Isabel Sánchez-Pérez , Adoracion G. Quiroga
{"title":"Antiproliferative activity in breast cancer cells of PtL2: A steroid-thiosemicarbazone platinum(II) complex","authors":"Jorge Melones-Herrero , Francisco Aguilar-Rico , Ana I. Matesanz , Carmela Calés , Isabel Sánchez-Pérez , Adoracion G. Quiroga","doi":"10.1016/j.jinorgbio.2025.112923","DOIUrl":"10.1016/j.jinorgbio.2025.112923","url":null,"abstract":"<div><div>Breast cancer remains one of the most diagnosed cancers in women worldwide. Metallodrugs such as cisplatin are used in advanced stages and hormone independent tumors. We hereby report the synthesis and characterization of a new benzaldehyde thiosemicarbazone functionalized with an estradiol derivative, LH, and two metal complexes, PdCl<sub>2</sub>(LH) and PtL<sub>2</sub>. Both complexes were studied in solution showing enough stability to further perform antitumoral activity studies. The Pd(II) complex was discarded for its poor performance while PtL₂ exhibited similar cytotoxic activity to cisplatin (CDDP) in estrogen receptor (+) and triple-negative breast cancer cells. Moreover, PtL₂ demonstrated reduced toxicity in healthy cell lines. It induced cell cycle arrest at the G0/G1 phase, distinguishing its mechanism of action from CDDP, which predominantly blocks cells in the S phase. Additionally, PtL₂ displayed a balanced intracellular distribution between the nucleus and cytoplasm, independent of estrogen receptor status. Further analysis revealed that PtL₂ dysregulated antioxidant enzyme expression, potentially disrupting redox homeostasis. These findings highlight PtL₂’s potential as a promising alternative to conventional platinum-based therapies, warranting further investigation into its molecular mechanisms and therapeutic applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112923"},"PeriodicalIF":3.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessandra Barbanente , Anna Maria Di Cosola , Mauro Niso , Luisa D'Anna , Simona Rubino , Sergio Indelicato , Concetta Pacifico , Alessio Terenzi , Nicola Margiotta
{"title":"New oxaliplatin-zoledronate derivatives with potential antitumor activity towards bone tumors and metastases","authors":"Alessandra Barbanente , Anna Maria Di Cosola , Mauro Niso , Luisa D'Anna , Simona Rubino , Sergio Indelicato , Concetta Pacifico , Alessio Terenzi , Nicola Margiotta","doi":"10.1016/j.jinorgbio.2025.112916","DOIUrl":"10.1016/j.jinorgbio.2025.112916","url":null,"abstract":"<div><div>Bone cancer can originate from any cellular element of the bone and may occur sporadically or as a result of degeneration from a precursor lesion. Bone metastases, often stemming from primary cancers such as breast and prostate cancer, are extremely painful and challenging to treat. The treatment of primary bone malignancies typically involves surgery, radiotherapy, chemotherapy and analgesics. Platinum (Pt)-based drugs are effective against bone cancers and metastases but are often limited by severe side effects due to poor specificity. To improve drug targeting and reduce systemic toxicity, bisphosphonate (BP) ligands, which selectively accumulate in bone tissue, have been combined with Pt-based drugs. The combination of Pt drugs with bisphosphonates like zoledronic acid (ZL) could lead to enhanced therapeutic outcomes due to its intrinsic pharmacological activity. In this study, we report the synthesis and full characterization of two new dinuclear Pt(II) complexes that combine ZL with clinically approved oxaliplatin and the drug-candidate kiteplatin, respectively. These complexes were tested for their stability under physiological and acidic conditions, reactivity with 5’-GMP interaction with B- and G-quadruplex DNA models and cytotoxicity against a panel of human tumor cell lines.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112916"},"PeriodicalIF":3.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandra Velásquez Bravo , Juan J. Martínez Medina , Libertad L. López Tevez , Andrés G. Restrepo , Ángel L. Huamaní , Pablo J. Gonzalez , Luciana G. Naso , Evelina G. Ferrer , Patricia A.M. Williams
{"title":"Structural related oxidovanadium(IV)-flavonoid complexes. Influence on their anticancer effects","authors":"Alexandra Velásquez Bravo , Juan J. Martínez Medina , Libertad L. López Tevez , Andrés G. Restrepo , Ángel L. Huamaní , Pablo J. Gonzalez , Luciana G. Naso , Evelina G. Ferrer , Patricia A.M. Williams","doi":"10.1016/j.jinorgbio.2025.112915","DOIUrl":"10.1016/j.jinorgbio.2025.112915","url":null,"abstract":"<div><div>Flavonoids, known for their antioxidant properties in plants, can also act as pro-oxidants in cancer cells, an effect that intensifies when coordinated with metal cations. Among them, oxidovanadium(IV) (VO) complexes with flavonoids have shown promising anticancer potential, following a clear relationship of the ligand structure with the activity. Quercetin and troxerutin share a common core structure; however, in troxerutin, four of the five hydroxyl (-OH) groups of quercetin are blocked, which may influence its metal coordination properties. In this study, we synthesized and fully characterized the VOtroxerutin complex using FTIR, EPR, UV–Vis, and reflectance spectroscopies, along with elemental, thermal, and conductivity analyses. Additionally, we prepared the reported VOquercetin complex, which shares the same coordination sphere as VOtroxerutin, to explore a relationship between the structure of the complexes and their activities. Their anticancer potential was tested through in vitro cytotoxicity assays against the A549 human lung cancer cells and HaCaT normal human keratinocytes. Both complexes exhibited anticancer activities (viability inhibition at 100 μM: 32.1 %, VOtroxerutin; 39.5 %,VOquercetin) and selectivity, highlighting their therapeutic potential. Notably, their pro-oxidant effects were activated upon incubation with cancer cells, leading to oxidative stress-induced cytotoxicity and mitochondrial membrane disruption. Further comparisons with the VOrutin complex provided additional insights into the correlation between anticancer activity and the coordination environment of the VOFlavonoid complexes. Additionally, we evaluated the safety profile of VOtroxerutin, finding no acute toxicity or mutagenic effects, supporting its potential as a targeted anticancer therapy with normal cells viability inhibition only at 100 μM (10 %).</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112915"},"PeriodicalIF":3.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marek Šebela , Giorgio Zoppellaro , Zdeněk Trávníček
{"title":"Copper(II) tetrapyrazole-based complex as a new peroxidase-mimetic compound","authors":"Marek Šebela , Giorgio Zoppellaro , Zdeněk Trávníček","doi":"10.1016/j.jinorgbio.2025.112911","DOIUrl":"10.1016/j.jinorgbio.2025.112911","url":null,"abstract":"<div><div>A copper(II) tetrapyrazole-based complex of the composition of [Cu(tpyr)(H<sub>2</sub>O)(ONO<sub>2</sub>)]NO<sub>3</sub> (<strong>1</strong>), where tpyr represents a tetradentate <em>N</em>-donor ligand formed by the condensation of 1<em>H</em>-pyrazole-5-carbaldehyde in NaOH/MeOH medium, has been prepared and characterized by elemental analysis, infrared spectroscopy, ultraviolet-visible spectroscopy, mass spectrometry, electron paramagnetic resonance and single-crystal X-ray diffraction. Spectrophotometric measurements demonstrated a remarkable peroxidase activity of the complex, which utilized hydrogen peroxide for the oxidation of phenolic compounds such as guaiacol or 3,5-dichloro-2-hydroxybenzene sulfonic acid. The optimum conditions for this reaction were found at pH 8 in ammonium bicarbonate buffer, although the activity was low but still detectable at pH 5–6 in ammonium acetate. As a peroxidase mimic, the complex exhibited enzyme-like Michaelis-Menten kinetics, showing a hyperbolic dependence of the reaction rate on hydrogen peroxide concentration. The determined <em>K</em><sub>m</sub> and <em>k</em><sub>cat</sub> values were 651 μmol·l<sup>−1</sup> and 6.7 × 10<sup>−4</sup> s<sup>−1</sup>, respectively, compared to 41 μmol·l<sup>−1</sup> and 73 s<sup>−1</sup> for horseradish peroxidase. EPR spectroscopy of the reaction mixture revealed no change in the copper (II) oxidation state during catalysis, suggesting that the oxidation of guaiacol may occur simultaneously with the reduction of hydrogen peroxide to water at the copper centre.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"268 ","pages":"Article 112911"},"PeriodicalIF":3.8,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}