Journal of Inorganic Biochemistry最新文献

{"title":"Three cobalt(II) complexes containing pyrimidylanthrahydrazone ligands: Synthesis, crystal structure, DNA binding, anticancer activity and structure-activity relationship","authors":"Jia-yu Xu ,&nbsp;Xue-bin Bi ,&nbsp;Sha-sha Luo,&nbsp;Yue Huang,&nbsp;Chen-yu Wang,&nbsp;Chang-chun Wen,&nbsp;Rui-xue Liu,&nbsp;Yan-cheng Liu,&nbsp;Hong Liang","doi":"10.1016/j.jinorgbio.2025.113158","DOIUrl":"10.1016/j.jinorgbio.2025.113158","url":null,"abstract":"<div><div>This research presents the design, synthesis, structural characterization, and evaluation of the anticancer activities of three new pyrimidylanthrahydrazone cobalt(II) complexes: <strong>1</strong>) 9-MPMAH-Co, <strong>2</strong>) 9-FPMAH-Co, and <strong>3</strong>) 9-PMAH-Co. Single-crystal X-ray diffraction analysis confirmed that all three complexes adopt a hexacoordinate mononuclear geometry. However, differences in their coordination modes were observed due to variations in the ligand substituents (-CH₃, -F, -H). Spectroscopic DNA interaction studies indicated that all three cobalt complexes exhibit varying levels of DNA intercalation. Topoisomerase I inhibition assays revealed that 9-PMAH-Co demonstrates significant enzyme inhibition at a low concentration of 1 μM. <em>In vitro</em> antiproliferative assays confirmed that 9-PMAH-Co exhibits potent cytotoxic activity against SK-OV-3 and HeLa-229 cancer cell lines, with IC₅₀ values of 4.99 ± 0.18 μM and 8.09 ± 1.13 μM, respectively, while showing reduced toxicity toward normal liver cells (HL-7702) compared to cisplatin. Further investigation through cell cycle analysis indicated that 9-PMAH-Co induces G2/M phase arrest in SK-OV-3 cells, with a population increase to 91.37 % (Δ = 76.59 %). Studies on the structural-activity relationship suggest that the synergistic interactions between the ligand substituents and the cobalt center play a crucial role in modulating biological activity, highlighting 9-PMAH-Co as a promising lead compound for the development of targeted anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113158"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666590","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":"The Neisseria gonorrhoeae cytochrome c2-bacterial peroxidase electron-transfer complex is competent in hydrogen peroxide reduction","authors":"Pedro M.S. Bragança ,&nbsp;Daniela S. Barreiro ,&nbsp;Marta S.P. Carepo ,&nbsp;Sofia R. Pauleta","doi":"10.1016/j.jinorgbio.2025.113164","DOIUrl":"10.1016/j.jinorgbio.2025.113164","url":null,"abstract":"<div><div><em>Neisseria gonorrhoeae</em> is a pathogenic bacterium responsible for the disease gonorrhea, which has gained increasing attention in recent years due to the emergence of strains resistant to the currently used antibiotics. In the absence of a vaccine, understanding mechanisms that contribute to infection is imperative. One such mechanism is the reduction of hydrogen peroxide by the outer membrane bound bacterial peroxidase. Here, steady-state kinetics shows that cytochrome <em>c</em>₂, previously implicated in nitrite reduction, is an efficient electron donor to this enzyme, proving to be an alternative to the lipid-modified azurin. The cytochrome <em>c</em>₂-mediated peroxidase activity has a <em>K</em>_M of 0.74 ± 0.08 μM and a <em>k</em>_<em>obs</em> of 18 ± 1 s⁻¹ for hydrogen peroxide, with an optimum pH at 7.7. The pH and ionic-strength dependence of this activity differs from that of azurin, suggesting that the two electron donors can play complementary roles depending on external conditions. Furthermore, the viscosity dependence of the activity suggests that protein-protein interactions are not purely diffusion-controlled but also governed by conformational changes required for complex formation and/or electron transfer, and docking analysis implies that cytochrome <em>c</em>₂ binds near the exposed edge of the electron transferring heme of the bacterial peroxidase.</div><div>This study improves our understanding of the periplasmic physiology of <em>N. gonorrhoeae</em> by demonstrating how the pathogen's flexibility in using electron donors enables it to maintain peroxidase activity and cope with oxidative stress in different host environments. These insights could inform future strategies aimed at disrupting redox homeostasis to combat antibiotic-resistant strains.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113164"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617586","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":"Benzothiazole diimine rhenium(I) ‘2 + 1’ complexes: Synthesis, structural characterization and anticancer activity","authors":"Ioanna Roupa ,&nbsp;Michael Kaplanis ,&nbsp;Antonio Shegani ,&nbsp;Barbara Mavroidi ,&nbsp;Nektarios Pirmettis ,&nbsp;Catherine Raptopoulou ,&nbsp;Vassilis Psycharis ,&nbsp;Aristeidis Chiotellis ,&nbsp;Maria Paravatou-Petsotas ,&nbsp;Maria Pelecanou ,&nbsp;Ioannis Pirmettis ,&nbsp;Minas Papadopoulos","doi":"10.1016/j.jinorgbio.2025.113185","DOIUrl":"10.1016/j.jinorgbio.2025.113185","url":null,"abstract":"<div><div>In this work, novel ‘2 + 1’ mixed ligand tricarbonyl Re^I complexes of the general type <em>fac</em>-[Re(CO)₃(NN)X]^0/+, where NN is a diimine ligand bearing the anticancer scaffold of 2-(4′-aminophenyl)benzothiazole, and X is Br⁻ (<strong>1</strong>), Η₂Ο (<strong>2</strong>), pyridine (<strong>3</strong>), cyclohexyl isocyanide (<strong>4</strong>), triphenylphosphine (<strong>5</strong>) and 1,3,5-triaza-7-phosphaadamantane (<strong>6</strong>), were synthesized, characterized, and evaluated. This design uses rhenium and phenylbenzothiazole to generate targeted, multipotent metal-based anticancer agents with tunable pharmacokinetics. Except for compound <strong>6</strong>, all complexes exhibited IC₅₀ values ranging from 0.19 to 6.28 μM against HeLa (ovarian), MCF-7 (breast), and A431 (epidermoid) cancer cell lines, outperforming cisplatin under the same conditions, while showing evidence of synergistic action between the pharmacophore and the rhenium core. In addition, their interaction with calf thymus DNA was investigated, with the data indicating intercalation. Complex <strong>4</strong>, with the most potent anticancer activity, was additionally labeled with ^99mTc and exhibited optimal stability and high lipophilicity. Its <em>in vivo</em> biodistribution was studied in healthy and SCID mice bearing MCF-7 xenografts, showing good tumor uptake and retention. Finally, a detailed X-ray crystallographic study of molecular packing revealed a plethora of intermolecular interactions, including hydrogen bonds, <em>π-π</em> overlap, and carbonyl···carbonyl interactions. The high anticancer potency and tumor-targeting properties make these compounds promising anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113185"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766758","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":"Unveiling the regio- and stereo-selectivity in situ primary amination of allylic and benzylic C(sp3)–H bonds: The pivotal role of structural evaluation","authors":"Yang Zeng ,&nbsp;Xue Jiang ,&nbsp;Yuxin Shi ,&nbsp;Yujun Si ,&nbsp;Lijun Yang","doi":"10.1016/j.jinorgbio.2025.113184","DOIUrl":"10.1016/j.jinorgbio.2025.113184","url":null,"abstract":"<div><div>Directed evolution of heme enzymes for the catalytic construction of benzylic C(sp³)–N bonds has attracted extensive attention. However, achieving regio- and stereoselective control in the enzyme-catalyzed C(sp³)–H activation step has remained a significant challenge. In this study, the potential energy surface defined by the transition state (TS) can appropriately illustrate the selective amination of C(sp³) − H at allylic or benzylic positions in certain reactive substrates, such as 1-phenyl-1-cyclohexene (<strong>a</strong>). However, this approach is not applicable to certain unreactive substrates, such as allylbenzene (<strong>l</strong>). A comprehensive understanding of the entire process requires methods capable of addressing highly multidimensional problems. Analysis of structural consistency suggested that, when both the attacking distance and angle are taken into account in the molecular dynamics (MD) simulation snapshots, conformations resembling the TS facilitate efficient hydrogen atom abstraction and site-selective enzymatic amination at the predicted positions. In contrast, the unreactive substrate rarely achieves a productive geometry conducive to C − H bond abstraction. Overall, these results highlight the selectivity that can arise due to the distinct geometrical requirements for efficient allylic or benzylic C − H bond amination mediated by cytochrome P450 enzymes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113184"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733820","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":"Impact of electrostatic distribution in CYP3A4 on the regioselectivity of triazolam metabolism and regulation of its metabolic rate by the iron spin states: Insights from MD simulations and QM calculations","authors":"Yan Zhao ,&nbsp;Xinyu Ma ,&nbsp;Qingchuan Zheng","doi":"10.1016/j.jinorgbio.2025.113162","DOIUrl":"10.1016/j.jinorgbio.2025.113162","url":null,"abstract":"<div><div>Triazolam (TRZ) is a representative benzodiazepine sedative-hypnotic drug that has gradually been abused due to the increasing societal pressures. To further provide a theoretical basis for the rationale use of TRZ and obtain more information for its metabolic process, in this study, human CYP3A4 was employed as the metabolic enzyme to investigate the metabolic mechanism of TRZ by multiple computational methods. Here, three types of substrate-binding conformations related to the diversity of TRZ metabolites are identified (pose A, pose B and pose C). The “sandwich” structure and the π-π stacking between TRZ and F304/porphyrin ring may be the key factors in dominating three substrate-binding conformations. Furthermore, we discovered pose A is the predominant binding mode, with Cα-H serving as the key metabolic site and CYP3A4-catalyzed Cα-H hydroxylation follows a hydrogen abstraction-rebound mechanism. More importantly, in hydroxylation process, the spin states of iron can regulate the metabolic reaction rate of TRZ and the highest rate of metabolism (5.96 s⁻¹) is found in the quartet spin states. Based on our findings, it can be suggested that rational incorporating aromatic groups into TRZ could improve its metabolic stability. Meanwhile, the transition of the heme iron from a low-spin to a high-spin state appears to accelerate TRZ metabolism, potentially leading to the accumulation of α-OH triazolam in vivo, which may pose risks to human health. These results could enhance our understanding of CYP3A4-mediated regioselective metabolism of TRZ and provide a theoretical foundation and new perspective for studies on the metabolism of other triazole drugs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113162"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617585","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":"Combined computational and bioinformatic approach to uncover the pre-covalent protein interactions of auranofin and its chlorido derivative Au(PEt₃)Cl","authors":"Iogann Tolbatov ,&nbsp;Alessandro Marrone","doi":"10.1016/j.jinorgbio.2025.113161","DOIUrl":"10.1016/j.jinorgbio.2025.113161","url":null,"abstract":"<div><div>Auranofin (AF) is a clinically approved gold(I) metallodrug with recognized anti-inflammatory and anticancer properties, whose mechanism of action relies on the covalent binding at key selenoproteins and thiols causing their irreversible deactivation. While the final covalent binding event is well-documented, the initial non-covalent recognition phase that precedes it, and which likely governs the drug's selectivity, remains poorly characterized by experimental methods. To address this gap, we employed density functional theory (DFT) calculations to systematically investigate the weak, pre-covalent interactions between auranofin (AF) or its chlorido derivative, Au(PEt₃ <!-->)Cl (AFCl), with model protein residues. Our results reveal distinct non-covalent interactions preferences for each drug: AF shows a stronger affinity for charged amino acid residues, while AFCl exhibits a marked preference for aromatic and some charged residues. We demonstrate that these initial non-covalent interactions induce a significant redistribution of electron density. This effect alters the local electronic properties of the gold center and its bond to the labile ligand, effectively priming the drug for subsequent covalent attack. We then utilized the computationally derived geometric assets to perform a comprehensive motif search within the Protein Data Bank (PDB) database, which identified ten protein targets with significant therapeutic relevance. This bioinformatic analysis provided a general picture of how these gold compounds navigate their biological environment and led to the identification of targets. This pre-covalent interaction with protein is not a random anchoring process but a crucial preparatory step for the targeted attachment of gold-based drugs.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113161"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617587","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":"An electrochemical perspective on human sulfite oxidase as a potential nitrite reductase","authors":"Peter D. Giang ,&nbsp;Joan Zapiter ,&nbsp;Jiayun Zhou ,&nbsp;Alexander T. Kaczmarek ,&nbsp;Günter Schwarz ,&nbsp;Paul V. Bernhardt","doi":"10.1016/j.jinorgbio.2025.113159","DOIUrl":"10.1016/j.jinorgbio.2025.113159","url":null,"abstract":"<div><div>The Mo-dependent enzyme human sulfite oxidase (HSO) oxidises highly neurotoxic sulfite to benign sulfate in the final step of cysteine catabolism. Although sulfite is its only known physiological substrate, HSO has been suggested to play a role in the generation of nitric oxide (NO) from nitrite under ischemic conditions. In this work we have investigated the electrochemically driven nitrite reductase activity of HSO mediated by the benzyl viologen radical cation. We show that HSO can act as an effective nitrite reductase with a <em>K</em>_M value of 3.5 mM at pH 7. A heme-free variant of HSO behaves similarly. We also demonstrate electrochemically driven tandem sulfite oxidation and nitrite reduction with HSO using a known Fe^III coordination compound as mediator. Significant pH-dependence of catalytic activity is found.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113159"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666498","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":"Assessment of the novel platinum(IV) complexes effects on female rats' kidneys: Possible nephroprotection of resveratrol","authors":"Milica G. Paunović ,&nbsp;Miloš M. Matić ,&nbsp;Ana D. Obradović ,&nbsp;Vesna D. Stanković ,&nbsp;Verica V. Jevtić ,&nbsp;Branka I. Ognjanović","doi":"10.1016/j.jinorgbio.2025.113137","DOIUrl":"10.1016/j.jinorgbio.2025.113137","url":null,"abstract":"<div><div>Due to cisplatin's limited efficacy and adverse effects on healthy tissues, particularly the kidneys, its use is restricted. The objective of this research was to investigate the impact of new Pt(IV) complexes that contain ethyl- propyl- and butyl-esters of the ethylenediamine-<em>N,N′</em>-di-<em>S,S</em>-(2,2′-dibenzyl) acetic acid, as well as possible advantages of resveratrol co-treatment, on the kidneys of female Wistar albino rats by detecting kidney injury markers, oxidative stress parameters and morphological tissue changes. The rats, divided into ten groups, received a single intraperitoneal dosage of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg), and/or resveratrol (25 mg/kg), whereas the control animals received only an ip injection of saline. Acute complexes treatments increased Chl value while decreasing Gl, Cre, and Urea levels, suggesting kidney injury. Novel compounds considerably decreased the levels of O₂^•−, H₂O₂ and GSSG, while raising the levels of NO₂⁻, LPO and GSH. In addition, the activities of SOD, GSH-Px, and GST were increased, while the activities of CAT and GR were alleviated. Regarding morphological changes in kidney tissue, they were mostly of mild intensity. Results indicate that used complexes might trigger an imbalance of redox equilibrium of kidney cells and that the renal tissue was more vulnerable to the negative effects of Pt(IV) complexes than to cisplatin. Resveratrol's nephroprotective benefits were not shown. Additionally, a prooxidative effect was registered after co-treatments. These findings could be useful for future studies in clarifying how the investigated compounds act in the estradiol-rich environment and how they affect the tissues of male rats.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113137"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517373","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":"Employing phosphonate and phosphinate ligands for prodrug development of the mitochondrial calcium uniporter inhibitor Ru265","authors":"Haipei Zou ,&nbsp;Samantha N. MacMillan ,&nbsp;Justin J. Wilson","doi":"10.1016/j.jinorgbio.2025.113145","DOIUrl":"10.1016/j.jinorgbio.2025.113145","url":null,"abstract":"<div><div>Ru265, [Ru₂(μ-N)(NH₃)₈Cl₂]Cl₃, is a potent nanomolar inhibitor of the mitochondrial calcium uniporter (MCU), the transporter that mediates Ca²⁺ uptake into the mitochondria. This compound and related MCU inhibitors are promising therapeutic agents and chemical biology tools for studying intracellular Ca²⁺ dynamics. Axial ligand modification of these Ru-based complexes provides a facile way to tune their properties and make prodrugs. In this study, the use of axial phosphonate and phosphinate ligands was explored within this compound class, yielding [Ru₂(μ-N)(NH₃)₈(OPO(OH)Me)₂](CF₃SO₃)₃ (<strong>1</strong>) and [Ru₂(μ-N)(NH₃)₈(OPOPh₂)₂](CF₃SO₃)₃ (<strong>2</strong>). Both complexes were characterized by multinuclear NMR spectroscopy, revealing downfield shifts of the ³¹P resonances of the coordinated ligands. The crystal structure of <strong>1</strong> was also obtained, which confirmed coordination of the methylphosphonate ligands to the axial sites of the Ru core. The aquation of <strong>1</strong> and <strong>2</strong> were studied by NMR and UV–vis spectroscopy. Unexpectedly, compound <strong>1</strong> undergoes partial aquation, arresting at a final product in which only one axial methylphosphonate is displaced by water. By contrast, <strong>2</strong> loses both diphenylphosphinates via aquation (t_1/2 = 1.7 h) under physiological conditions. The in vitro biological investigations of <strong>1</strong> and <strong>2</strong> in HeLa cells showed that neither demonstrate high cytotoxicity nor depolarize the mitochondrial membrane potential. Both compounds exhibit nanomolar inhibitory activity against mitochondrial Ca²⁺ uptake in permeabilized HEK293T cells and modest inhibitory activity against this process in intact HeLa cells. Notably, <strong>1</strong> shows pH-dependent activity for MCU inhibition, with greater inhibition in more acidic conditions, while <strong>2</strong> shows improvement in cellular uptake efficiency.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113145"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562227","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":"Copper(II) and zinc(II) complexes of dimeric 8-hydroxyquinoline ligands: Synthesis, metal speciation, and biological evaluation","authors":"Roberta Panebianco ,&nbsp;Giuseppina D.G. Santonoceta ,&nbsp;Roberta Borrelli ,&nbsp;Maria G.G. Pittalà ,&nbsp;Rosaria Saletti ,&nbsp;Carmelo Sgarlata ,&nbsp;Maurizio Viale ,&nbsp;Salvatore Furnari ,&nbsp;Virginia Fuochi ,&nbsp;Pio M. Furneri ,&nbsp;Tommaso Mecca ,&nbsp;Graziella Vecchio","doi":"10.1016/j.jinorgbio.2025.113138","DOIUrl":"10.1016/j.jinorgbio.2025.113138","url":null,"abstract":"<div><div>Hydroxyquinolines have garnered considerable attention due to their biomedical potential, particularly their ability to coordinate metal ions, which significantly influences their biological activity.</div><div>In this study, a series of 8-hydroxyquinoline dimeric derivatives was synthesized and compared to their monomeric counterparts. The metal-binding properties of these compounds with zinc(II) and copper(II) ions were investigated using ESI-MS spectrometry and UV–Vis spectrophotometry. The results revealed that 8-hydroxyquinoline dimers form highly stable metal complexes.</div><div>Biological studies have demonstrated that the functionalization of the 8-hydroxyquinoline scaffold modulates its activity: the introduction of amine chains in monomeric systems decreases the antiproliferative effects, both in the ligands and their metal complexes. Notably, the dimer derivative linked <em>via</em> diaminoethane exhibited the most potent antiproliferative and antibacterial activities. In contrast, the introduction of a diaminodioxaoctane linker reduced toxicity in bacteria and cancer cells, highlighting its promise as a biologically compatible metal-chelating agent.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"275 ","pages":"Article 113138"},"PeriodicalIF":3.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463311","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}