Journal of Inorganic Biochemistry最新文献

{"title":"On the structural, photophysical and antimicrobial properties of bimetallic Re-Fe coordination compounds bearing diimines ligands","authors":"Emilia R. Serrano ,&nbsp;Pedro M. David Gara ,&nbsp;Juan J. Martínez Medina ,&nbsp;Filippo Prencipe ,&nbsp;Oscar E. Piro ,&nbsp;Gustavo A. Echeverría ,&nbsp;Gabriela Petroselli ,&nbsp;Tatiana Da Ros ,&nbsp;Gustavo T. Ruiz","doi":"10.1016/j.jinorgbio.2025.113178","DOIUrl":"10.1016/j.jinorgbio.2025.113178","url":null,"abstract":"<div><div>A new complex <em>fac</em>-[(ferroceneCO₂)Re^I(CO)₃(dppz)] (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) was obtained and fully characterized by elemental analysis, ¹H and ¹³C NMR, ESI-mass, IR and UV–vis spectroscopy. We also report new insights into the structural and photophysical properties of the <em>fac</em>-[(ferroceneCO₂)Re^I(CO)₃L], where L = 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen), parent complexes. For all complexes, our results showed that: (i) no singlet oxygen generation was detected in acetonitrile solutions and (ii) they exhibited a very low luminescence quantum yield. However, photoacoustic measurements showed that under photoexcitation the complexes released all the absorbed energy to the medium as prompt heat. The antimicrobial activity of the ferroceneCO₂-Re(CO)₃(phen) complex was detected against both bacteria from American Type Culture Collections (ATCC) and clinically isolated bacterial strains. Antibacterial activity was rationalized in relation to extension of the π-system of the diamine ligands. Additionally, the ferroceneCO₂-Re(CO)₃(phen) complex showed no mutagenic potential.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113178"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733863","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":"Special issue on “Metal complexes targeting non-canonical nucleic acid structures”","authors":"Riccardo Bonsignore,&nbsp;Alessio Terenzi","doi":"10.1016/j.jinorgbio.2025.113186","DOIUrl":"10.1016/j.jinorgbio.2025.113186","url":null,"abstract":"","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113186"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888402","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":"Aromatic amino acid based Schiff base copper(II) complexes as potential lung cancer therapeutics: Biological and antioxidant activity, DNA/BSA interaction, mesogenic properties, molecular docking and DFT study","authors":"Hunshisha Pyngrope ,&nbsp;Jagritima Chetia ,&nbsp;Bandashisha Kharpan ,&nbsp;Snehashish Modak ,&nbsp;Tamanna Aktar ,&nbsp;Amit Kumar Pradhan ,&nbsp;Akhilesh Jaiswar ,&nbsp;Pradip C. Paul ,&nbsp;Debasish Maiti","doi":"10.1016/j.jinorgbio.2025.113187","DOIUrl":"10.1016/j.jinorgbio.2025.113187","url":null,"abstract":"<div><div>Three new copper(II) complexes, Cu(L¹)₂, Cu(L²)₂, and Cu(L³)₂, derived from aromatic amino acid based Schiff base ligands, potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-phenylpropanoate (HL¹), potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-(4-hydroxyphenyl) propanoate (HL²) and potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-(1H-indol-2-yl)propanoate (HL³) were synthesized and characterized by using elemental analysis and the spectroscopic techniques viz., UV–visible, ¹³C NMR, ¹H NMR, FT-IR spectroscopy. All three complexes interact effectively with calf thymus-deoxyribonucleic acid (CT-DNA) and Bovine serum albumin (BSA), as evidenced from spectroscopic studies. Among them, Cu(L³)₂ exhibited the strongest biomolecular binding affinity, highest cytotoxic activity against lung adenocarcinoma (A-549) cells, and superior antioxidant capacity in the DPPH (2,2-diphenyl-1-picryhydrazyl) assay. Molecular docking simulations were carried out to evaluate the binding affinity and interaction profiles of aromatic amino acid-based Schiff base Cu(II) complexes with Human Serum Albumin (HSA). The results revealed selective binding at Sudlow's site I, with the binding of Cu(L³)₂ with HSA exhibiting the highest affinity (−5.81 kcal mol⁻¹). The parent ligands HL¹, HL² and HL³ exhibit blue photoluminescence, and the presence of their long alkyl chain substituents induced mesomorphic behaviour with distinct nematic, smectic C, and mosaic textures, respectively. Density functional theory (DFT) calculations supported the experimental findings, revealing optimized geometries and HOMO–LUMO band gaps consistent with their reactivity trends. On the whole, Cu(L³)₂ emerges as the most promising candidate for biomedical applications, while the ligands themselves show potential for functional mesogenic material.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113187"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773238","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":"Additional functionality for plecstatin-1-analogous anticancer Ru(η6-p-cymene)Cl complexes","authors":"Shahid Iqbal ,&nbsp;Adnan Ashraf ,&nbsp;Anne Dill ,&nbsp;Zexiong Lin ,&nbsp;Sanam Movassaghi ,&nbsp;Muhammad Hanif ,&nbsp;Waseeq Ahmad Siddiqui ,&nbsp;Stephen M.F. Jamieson ,&nbsp;Christian G. Hartinger","doi":"10.1016/j.jinorgbio.2025.113168","DOIUrl":"10.1016/j.jinorgbio.2025.113168","url":null,"abstract":"<div><div>The bioactivity of organometallic compounds can be enhanced by modifying the ligand to achieve higher potency or an altered mode of action. Here, we conjugated amino acids to pyridine-2-carbothioamides (PCAs) and formed their Ru^II(<em>cym</em>)Cl (cym = η⁶-<em>p</em>-cymene) organometallics, as confirmed by mass spectrometry, NMR spectroscopy and elemental analysis. The <em>in vitro</em> antiproliferative activities of ligands <strong>1–4</strong> and complexes <strong>1a</strong>–<strong>4a</strong> were established against human non-small cell lung carcinoma (NCI-H460), cervical carcinoma (SiHA), colorectal carcinoma (HCT116) and colon adenocarcinoma (SW480) cell lines. Complexes <strong>1a–3a</strong> showed no activity but <strong>4a</strong> was moderately potent with an IC₅₀ value of 35 μM in NCI-H460 cells. Organoruthenium compound <strong>4a</strong> was also more active than its PCA ligand <strong>4</strong> and the clinically investigated Ru complex KP1339 in NCI-H460 cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113168"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733862","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":"Potential water-soluble metal phthalocyanine candidates for the treatment of Alzheimer's disease: Synthesis, cholinesterase enzyme inhibition, kinetic analysis and cytotoxicity against human neuroblastoma (SH-SY5Y)","authors":"Turgut Keleş ,&nbsp;Zekeriya Biyiklioglu ,&nbsp;Gökçe Seyhan ,&nbsp;Elif Öz ,&nbsp;Rengin Reis ,&nbsp;Burak Barut","doi":"10.1016/j.jinorgbio.2025.113197","DOIUrl":"10.1016/j.jinorgbio.2025.113197","url":null,"abstract":"<div><div>In this study, manganese (III), cobalt (II), copper (II) and zinc (II) phthalocyanines and their quaternized cationic derivatives bearing morpholine groups in the non-peripheral position were producedand characterized by various spectroscopic techniques such as UV–Vis, FT-IR, ¹H and ¹³C NMR (only for Zn(II)), MALDI-TOF mass spectra. The inhibitory potential of new compounds on AChE and BuChE enzymes was investigated and IC₅₀ values were determined. It was found that water-soluble derivatives showed stronger inhibitory properties. The most effective compounds in AChE inhibition were water-soluble zinc (II) phthalocyanine (<strong>ZT6Q)</strong> (IC₅₀ = 0.85 ± 0.18 μM) and water-soluble manganese (III) phthalocyanine <strong>ZT3Q</strong> (IC₅₀ = 2.26 ± 0.38 μM), while <strong>ZT6Q</strong> showed the strongest effect in BuChE inhibition (IC₅₀ = 5.15 ± 0.48 μM). Lineweaver-Burk analyses revealed that these compounds inhibited both enzymes in a mixed manner. <em>K</em>_<em>i</em> and <em>K</em>_<em>ii</em> values were also calculated. In cell viability tests against human neuroblastoma (SH-SY5Y), <strong>ZT6Q</strong> did not show cytotoxic effects up to 10 μM, on the contrary, they increased cell viability. However, <strong>ZT3Q</strong> exhibited higher cytotoxicity at 48 h exposure. The findings indicate that these compounds can be evaluated as potential therapeutic agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113197"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787258","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":"Deciphering Cu(II) EPR in biological buffers: Implications for copper protein studies","authors":"Guodong Rao ,&nbsp;Lizhi Tao ,&nbsp;R. David Britt","doi":"10.1016/j.jinorgbio.2025.113192","DOIUrl":"10.1016/j.jinorgbio.2025.113192","url":null,"abstract":"<div><div>Copper proteins are essential for many biological processes, mediating electron transfer and redox catalysis in biochemistry and playing key roles in human health. Electron paramagnetic resonance (EPR) spectroscopy is a powerful tool to probe Cu(II) centers in these proteins, but its application can be complicated by spurious signals arising from adventitious Cu(II) binding to buffers or affinity tags. Here, we systematically examined Cu(II) EPR signals from common biological buffers (Tris, HEPES, MOPS) over pH 6.0–8.0, as well as from a His affinity tag. We show that Tris coordinates Cu(II) across this pH range, whereas HEPES binds Cu(II) weakly at near neutral pH and MOPS essentially does not chelate Cu(II) and rather precipitates Cu(II). These buffer-dependent Cu(II) complexes produce distinct EPR signatures that can interfere with spectral interpretation and spin quantifications. Using two case studies—a bacterial multicopper oxidase (MnxEFG) and <em>Drosophila</em> lysyl oxidase (DmLOX), we show how buffer choices and purification tags influence the observed Cu EPR spectra. In MnxEFG, switching from HEPES to Tris eliminated adventitiously bound Cu(II) and revealed the true copper content and sites. In DmLOX, we identified an EPR signature of Cu(II) bound to the protein's His-tag, which could be minimized by appropriate refolding conditions. These findings highlight the importance of controlling solution chemistry during sample preparation and suggest practical strategies to obtain cleaner, more interpretable spectra. Overall, this work provides guidance for minimizing nonspecific Cu(II) binding and improving the reliability of EPR analysis in studies of copper proteins in biological systems.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113192"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787259","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":"High antioxidant and antibiofilm activity of manganese (II and III) complexes derived from pyridoxal and aromatic hydrazides","authors":"Josiéli Demetrio Siqueira ,&nbsp;Yuri Clemente Andrade Sokolovicz ,&nbsp;Morgana Maciél Oliveira ,&nbsp;Francisco Mainardi Martins ,&nbsp;Marieli Friedrich Loreto ,&nbsp;Fallon dos Santos Siqueira ,&nbsp;Otávio Augusto Chaves ,&nbsp;Marli Matiko Anraku de Campos ,&nbsp;Davi Fernando Back","doi":"10.1016/j.jinorgbio.2025.113166","DOIUrl":"10.1016/j.jinorgbio.2025.113166","url":null,"abstract":"<div><div>This work presents the synthesis and characterization of seven novel Mn^II/Mn^III-complexes (<strong>C1</strong>–<strong>C7</strong>), including one dimeric species, and investigates their potential biological applications. The Mn^II/III complexes were obtained from Schiff base ligands derived from the condensation of pyridoxal hydrochloride with <em>para</em>-substituted aromatic hydrazides. These ligands provided versatile coordination environments, leading to the formation of structurally diverse manganese complexes. All compounds were thoroughly characterized by spectroscopic techniques, elemental analysis, and single-crystal X-ray diffraction for selected examples. In silico calculations were carried out to identify the possible biological activities of the synthetic inorganic compounds, being the antioxidant activity of the Mn^II/III-complexes validated with the nitro blue tetrazolium chloride (NBT) photoreduction assay (superoxide dismutase (SOD)-mimetic behavior). Among the series, complex <strong>C6</strong> exhibited the most efficient inhibition of superoxide. Furthermore, the antimicrobial potential of the complexes was thoroughly evaluated through in vitro assays against clinically relevant standard strains commonly used in reference protocols, as well as multidrug-resistant (MDR) clinical isolates (resistant to three or more classes of antimicrobials used in clinical practice), representing medically important pathogens with significant therapeutic challenges. In this case, <strong>C6</strong> had excellent antimicrobial activity, highlighting its potential as a multitarget candidate. Overall, these results bring to light the multifunctional potential of Mn^II/Mn^III-complexes based on pyridoxal-derived ligands for biomedical applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113166"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766763","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":"Optimization of bulkiness/dynamicity and pH utilizing N,N′-bis(5,6,7-trimethoxy-2-quinolylmethyl)-N,N′-dialkylethylenediamines as a Cd2+-specific fluorescent sensor","authors":"Yuji Mikata ,&nbsp;Saori Yasuda ,&nbsp;Poonyawee Suwankeeree ,&nbsp;Runo Ozaki ,&nbsp;Hideo Konno ,&nbsp;Takashi Matsuo ,&nbsp;Sunao Shoji","doi":"10.1016/j.jinorgbio.2025.113194","DOIUrl":"10.1016/j.jinorgbio.2025.113194","url":null,"abstract":"<div><div>Two methyl substituents of TriMeOBQDMEN (<strong>L0</strong>, <em>N,N′</em>-bis(5,6,7-trimethoxy-2-quinolylmethyl)-<em>N,N′</em>-dimethylethylenediamine) have been changed to 3-pentyl, cyclopentyl, and cyclohexyl groups to achieve better Cd²⁺ selectivity on fluorescence enhancement upon metal ion binding. Bulky alkyl substituents result in weak metal binding affinity of the ligand, which decreases the fluorescence intensity in the presence of excess amount of metal salt, even for Cd(ClO₄)₂ in DMF-H₂O (1:1). During the titration, the protons generated in the presence of excess metal perchlorate inhibit the complexation by protonation of the ligand. Addition of chloride ion minimizes the fluorescence drop in the presence of excess cadmium salt via formation of dinuclear bis(μ-chloro) cadmium complex. Intrinsic fluorescent Cd/Zn selectivity of the ligand can be assessed in DMF-HEPES buffer (1:1, 50 mM HEPES, 0.1 M KCl, pH = 7.5). The use of DMF-borate buffer (1:1, 50 mM M boric acid, 50 mM KCl, pH = 10) effectively discriminates Cd²⁺ from Zn²⁺ (<em>I</em>_Zn/<em>I</em>_Cd = 0.7 % in the presence of 3 equiv. of metal ions) by utilizing the TriMeOBQDPEN (<strong>L2</strong>, <em>N,N′</em>-bis(5,6,7-trimethoxy-2-quinolylmethyl)-<em>N,N′</em>-di(3-pentyl)-ethylenediamine) with moderate metal binding affinity. Lowering pH also increases the Cd²⁺ selectivity (<em>I</em>_Zn/<em>I</em>_Cd = 9 % in the presence of 5 equiv. of metal ions) of TriMeOBQDCPEN (<strong>L3</strong>, <em>N,N′</em>-bis(5,6,7-trimethoxy-2-quinolylmethyl)-<em>N,N′</em>-di(cyclopentyl)ethylenediamine) in DMF-glutarate buffer (1:1, 10 mM 3,3-dimethylglutaric acid, 0.1 M NaCl, pH = 6).</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113194"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786845","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 new interpretation for oxygen atom-transfer reactions for the Berg-Holm Oxomolybdenum enzyme model: Evidence for a highly active oxygen atom transfer acceptor","authors":"Jeremy M. Berg","doi":"10.1016/j.jinorgbio.2025.113163","DOIUrl":"10.1016/j.jinorgbio.2025.113163","url":null,"abstract":"<div><div>In 1984, a synthetic model system for certain molybdenum oxotransferase enzymes was reported. These reports claimed that an oxygen atom could be extracted from a designed dioxomolybdenum(VI) complex to produce a monoxomolybdenum(IV) complex without the formation of an oxo-bridged molybdenum(V) binuclear species. The reduced product was shown to accept oxygen atoms from substrates such as dimethylsulfoxide with substrate saturation kinetics. Fifteen years later, it was demonstrated that the reduced product was, in fact, the oxo-bridged molybdenum(V) binuclear species. Here, it is shown that the kinetic data can be reinterpreted in terms of rate-limiting disproportionation of the oxo-bridged molybdenum(V) binuclear species to form a highly reactive monoxomolybdenum(IV) complex. The second order rate constant for oxygen atom transfer from dimethyl sulfoxide to this complex is more than 100,000 times higher than those reported for other monoxomolybdenum(IV) complexes. The five-coordinate molybdenum sites in the dioxomolybdenum(VI) and presumed monoxomolybdenum(IV) complexes are quite similar to those observed for eukaryotic nitrate reductase enzymes and this model system shows relatively rapid reduction of nitrate through a similar mechanistic scheme.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113163"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659972","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":"Potent anticancer 5-fluorouracil platinum(IV) prodrugs","authors":"Aleen Khoury ,&nbsp;Maria George Elias ,&nbsp;Jennette A. Sakoff ,&nbsp;Jayne Gilbert ,&nbsp;Kieran F. Scott ,&nbsp;Janice R. Aldrich-Wright","doi":"10.1016/j.jinorgbio.2025.113165","DOIUrl":"10.1016/j.jinorgbio.2025.113165","url":null,"abstract":"<div><div>Six platinum(IV) prodrugs incorporating 5-fluorouracil (5FU) derivatives in the axial positions were synthesised, purified, fully characterised, and their biological activity assessed. The 5FU derivatives, 5FU-acetate and 5FU-methoxybutanoate, were successfully coordinated to [Pt(P_L)(1<em>S</em>,2<em>S</em>-diaminocyclohexane)(OH)₂]²⁺ scaffolds, where P_L = 1,10-phenanthroline (Phen) or 5,6-dimethyl-1,10-phenanthroline (56Me₂Phen). All complexes exhibited exceptional <em>in vitro</em> cytotoxicity across a broad panel of cancer cell lines, with [Pt^IV(56Me₂Phen)(1<em>S</em>,2<em>S</em>-diaminocyclohexane)(5FU-methoxybutanoate)(OH)](NO₃)₂ (<strong>6</strong>) demonstrating the lowest GI₅₀ of 1 nM against the prostate Du145 cancer cell line. Each complex displayed significantly enhanced activity compared to cisplatin, with <strong>6</strong> being up to 1400-fold more active in selected cancer cell lines. Complexes incorporating the 5FU-methoxybutanoate ligand (<strong>5</strong> and <strong>6</strong>) were notably more cytotoxic and lipophilic than their 5FU-acetate analogues (<strong>1</strong>–<strong>3</strong>), with <strong>6</strong> also exhibiting ∼2-fold greater potency than its platinum(II) precursor. Further studies in the HT29 colon cancer cell line revealed that <strong>5</strong> and <strong>6</strong> induced sustained elevations in reactive oxygen species (ROS) and substantial reductions in mitochondrial membrane potential, indicating that oxidative stress and mitochondrial dysfunction contributed to their cytotoxicity. Collectively, these findings demonstrate that the incorporation of 5FU into platinum(IV) prodrugs enhances both potency and mechanistic activity, with prodrug <strong>6</strong> emerging as a highly promising anticancer candidate.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113165"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646945","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}