Journal of Inorganic Biochemistry最新文献

{"title":"Targeted gadolinium-labeled gold nanoparticles for MR imaging of C-reactive protein","authors":"Naedum I. DomNwachukwu ,&nbsp;Matthew D. Bailey ,&nbsp;Minrui Luo ,&nbsp;Jonathan Schiff ,&nbsp;Andrew Brotherton ,&nbsp;Bennet Phillips-Sorich ,&nbsp;Jonathan Rivnay ,&nbsp;Thomas J. Meade","doi":"10.1016/j.jinorgbio.2025.113195","DOIUrl":"10.1016/j.jinorgbio.2025.113195","url":null,"abstract":"<div><div>C-reactive protein (CRP) is rapidly upregulated during the early stages of inflammation following injury, infection, or illness and binds to damaged cells in affected tissues, making it an attractive target for imaging. Current clinical assays measure only circulating CRP levels and provide no spatial information about the location of inflammation or its structural impact. Direct visualization of CRP in tissues could enable earlier detection, precise localization of pathology, monitoring of treatment response, and identification of subclinical disease. Here, we report the development of the first CRP-targeted magnetic resonance (MR) imaging contrast agent for molecular imaging of inflammation. We synthesized a gadolinium-labeled gold nanoparticle (AuNP) targeted to CRP through a phosphocholine (PC) ligand, termed PC-Gd@AuNP. The resulting particles were highly uniform (∼2 nm) with a tunable Gd:PC surface ratio. Biophysical characterization demonstrated strong binding affinity for CRP (K_D = 135 ± 63.96 nM) and specificity in a complex biological fluid model. PC-Gd@AuNPs displayed high longitudinal relaxivity (8.5 mM⁻¹ s⁻¹ per Gd) and cytotoxicity thresholds (LC₅₀) of 1 μM in HeLa cells and 0.284 μM in HepG2 cells. These findings establish PC-Gd@AuNPs as a promising molecular MRI contrast agent with the potential to directly image CRP deposition in inflamed tissues and advance noninvasive detection and monitoring of inflammatory diseases.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113195"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809110","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 oxidizing reactivity of mononuclear nonheme Iron(V)-oxo complexes","authors":"Dahyeon Ha ,&nbsp;Akhilesh Kumar ,&nbsp;Young Hyun Hong ,&nbsp;Yong-Min Lee ,&nbsp;Shunichi Fukuzumi ,&nbsp;Wonwoo Nam","doi":"10.1016/j.jinorgbio.2025.113143","DOIUrl":"10.1016/j.jinorgbio.2025.113143","url":null,"abstract":"<div><div>Mononuclear nonheme iron(V)-oxo complexes bearing a tetraamido-macrocyclic (TAML) ligand ([Fe^V(O)(TAML)]⁻) are well characterized and the high oxidizing reactivity has been examined. In contrast, the oxidizing reactivity of mononuclear nonheme iron(V)-oxo complexes with neutral ligands, has yet to be studied because of the extreme short lifetimes of the iron(V)-oxo complexes (ca. several microseconds). We report herein systematic studies on the oxidizing reactivity of formal mononuclear nonheme iron(V)-oxo complexes, [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ [<em>n</em> = 2 where L is neutral ligand or <em>n</em> = 1 where L is monoanion ligand], by using laser-induced transient absorption measurements. The [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ complexes were produced by electron transfer from [Fe^IV(O)(L)]ⁿ⁺ to the triplet excited state of 2,3-dichloro-5,6-dicyano-<em>p</em>-benzoquinone (³DDQ*), which was generated by laser excitation. [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ reacts with H₂O to produce [Fe^III(OOH)(L)]ⁿ⁺, which was further oxidized by DDQ to evolve O₂, accompanied by regeneration of [Fe^II(L)]ⁿ⁺. The decay rates of [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ became faster in the presence of substrates via oxidation of substrates by [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺. Plots of logarithm of the rate constants vs the one-electron oxidation potentials of donor substrates were evaluated in light of the Marcus theory of outer-sphere electron transfer to afford the one-electron reduction potentials and reorganization energies of [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺, which have been compared with those of other iron(V)-oxo complexes. The large reorganization energies of the electron-transfer reduction of the one-electron oxidized species of [Fe^IV(O)(L)]ⁿ⁺ indicate that electron-transfer oxidation of [Fe^IV(O)(L)]ⁿ⁺ occurs at the metal center to produce [Fe^V(O)(L)]⁽ⁿ⁺¹⁾⁺ rather than [Fe^IV(O)(L^•+)]⁽ⁿ⁺¹⁾⁺.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113143"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733864","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":"Structure-activity relationships in catalytic amyloids","authors":"Shams Aaghaz,&nbsp;Liam R. Marshall,&nbsp;Ivan V. Korendovych","doi":"10.1016/j.jinorgbio.2025.113193","DOIUrl":"10.1016/j.jinorgbio.2025.113193","url":null,"abstract":"<div><div>Short peptide-based assemblies combined with metal ions are simple yet effective platforms for catalysis. This study investigates the catalytic properties of <em>de novo</em> amyloid forming peptides, how their catalytic properties change with a range of hydrolysis substrates and the relationship between catalysis and structural characteristics. We have shown that even slight modifications in peptide sequence have a drastic impact on catalytic efficiency and substrate selectivity. We have also established k_uncat benchmarks for a 4-methylumbelliferyl ester that is increasingly reported as a model substrate in protein design studies. Our studies have yielded catalytic amyloids which display levels of specific activity on par with those reported for the best <em>de novo</em> globular enzymes. This work expands the understanding of catalytic amyloid function and explores design principles for developing minimal peptide scaffolds with tunable esterase-like activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113193"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786846","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":"Rare examples of rhenium(I) tricarbonyl iodido complexes with unsymmetrical bipyridines featuring distinguishable rotamers: From synthesis and solid-state/solution-phase isomerism to biological activity","authors":"Enis Šuta ,&nbsp;Adnan Zahirović ,&nbsp;Vele Tešević ,&nbsp;Sanja Grgurić-Šipka ,&nbsp;Sandra Aranđelović ,&nbsp;Sead Ljubijankić ,&nbsp;Jovana Ljujić ,&nbsp;Milica Balaban ,&nbsp;Armin Hrnjić ,&nbsp;Aleksandar Višnjevac ,&nbsp;Nevzeta Ljubijankić","doi":"10.1016/j.jinorgbio.2025.113167","DOIUrl":"10.1016/j.jinorgbio.2025.113167","url":null,"abstract":"<div><div>Three novel unsymmetrically substituted 2,2′-bipyridine ligands were prepared by introducing a 2-hydroxyphenyl group at the 6-position and either a 4-methoxyphenyl, 3,4-dimethoxyphenyl or 3,4-methylenedioxyphenyl group at the 4-position, using a modified Kröhnke protocol. Their corresponding rhenium(I) tricarbonyl iodido complexes, <em>fac</em>-[Re(L)(CO)₃I], <strong>1</strong>–<strong>3</strong>, were synthesized and comprehensively characterized by single-crystal X-ray diffraction (SCXRD), ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, ultraviolet–visible (UV–Vis) spectroscopy, cyclic voltammetry (CV), high-resolution mass spectrometry (HRMS), and elemental analysis. The common 6-(2-hydroxyphenyl) moiety predominantly influences the spectroscopic and redox properties of the complexes. SCXRD confirms the facial arrangement of the <em>fac</em>-[Re(CO)₃N₂I] core in all three cases, although solid-state conformational isomerism was observed only in complex <strong>1</strong>. In contrast, two NMR-distinguishable isomers are observed in solution for all three complexes. The cytotoxicity of <strong>1</strong>–<strong>3</strong> was evaluated by MTT assay after 48 h of continuous exposure in several human tumor cell lines (HeLa, PANC-1, MDA-MB-231, A549) and in non-malignant human lung fibroblasts (MRC-5). Notably, all three complexes displayed low-micromolar IC₅₀ values comparable to cisplatin, with the highest activity observed in HeLa cells (5.11–7.45 μM). However, significant activity was also recorded in MRC-5 cells (IC₅₀ = 8.19–8.95 μM), suggesting higher overall toxicity and weaker selectivity compared to cisplatin. Analysis in HeLa cells using bright-field microscopy confirmed a substantial antiproliferative effect.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113167"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145646972","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":"NMR investigation on the non-enzymatic breakdown of the glucosinolate sinigrin and its acetylated derivative by copper ions","authors":"Laurenzo D.V. Alba ,&nbsp;Tsubasa Hatanaka ,&nbsp;Tatsuo Yajima ,&nbsp;Shigenobu Yano ,&nbsp;Yasuhiro Funahashi","doi":"10.1016/j.jinorgbio.2025.113181","DOIUrl":"10.1016/j.jinorgbio.2025.113181","url":null,"abstract":"<div><div>Copper is an essential trace element present in many organisms, and the maintenance of its homeostasis is involved in the prevention of diseases, including cancer. Glucosinolates are sulfur-containing glycosides mainly found in cruciferous plants, and are hydrolyzed by the myrosinase enzyme to bioactive compounds such as isothiocyanates that contribute to plant defense against herbivores and exhibit various health-promoting effects in humans. The interaction between Cu and glucosinolates, however, is largely uncharacterized. In this ¹H nuclear magnetic resonance (NMR)-based study, we demonstrated that the glucosinolate sinigrin or its <em>O</em>-acetylated derivative can readily react with Cu(I) ions in solution without the presence of the plant myrosinase enzyme, although Cu(II) ions were found to be unreactive. In aqueous solution, the Cu(I) ions interact with the vinyl group of sinigrin as shown by ¹H NMR spectroscopy. The glycosidic C<img>S bond of sinigrin is eventually cleaved, resulting in the formation of 2-butenenitrile. The reaction can also occur in the presence of Cu(II) and ascorbic acid generating Cu(I) in situ. When the reaction is conducted without triflate in organic solvent, Cu(I) ions were also demonstrated to be able to desulfate <em>O</em>-acetylated sinigrin without cleavage of the glycosidic C<img>S bond. Our findings indicate that Cu(I)-mediated non-enzymatic cleavage plays a key role in the fate of dietary glucosinolates and suggest that these compounds and their hydrolysis products may help sequester excess copper. This study will be developed for other glucosinolates with additional spectroscopic, chromatographic, and analytical methods for further understanding.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113181"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733819","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":"Dehalogenation activity of a miniaturized peroxidase: substrate dependent functional switch","authors":"Maria De Fenza ,&nbsp;Linda Leone ,&nbsp;Matilde Tancredi ,&nbsp;Edelberto Oscar Niola ,&nbsp;Ornella Maglio ,&nbsp;Gerardino D'Errico ,&nbsp;Flavia Nastri ,&nbsp;Daniele D’Alonzo ,&nbsp;Angela Lombardi","doi":"10.1016/j.jinorgbio.2025.113154","DOIUrl":"10.1016/j.jinorgbio.2025.113154","url":null,"abstract":"<div><div>Natural peroxidases use 4-halophenols either as substrates in oxidative chemistry or as inhibitors. Herein, we demonstrated that Fe-mimochrome VI*a (Fe-MC6*a), a miniaturized heme-enzyme, is a versatile catalyst as it integrates both these features. We previously reported that Fe-MC6*a catalyzes the chemo- and regio-selective oxidation of 4-halophenols, providing either dehalogenation or oligomerization products, depending on the nature of the halogen atom. In particular, 4-chlorophenol (4-CP) and 4-fluorophenol (4-FP) selectively led to dehalogenation and oligomerization products, respectively. Herein, spin-trapping studies and EPR analysis confirm the ability of Fe-MC6*a into processing halophenols as substrates and provide mechanistic hypothesis for the chemo-divergent reaction outcome. Further, in multiple substrate competition assays, 4-halophenols act as competitive inhibitors of Fe-MC6*a-catalyzed dehalogenation of 2,4,6-trichlorophenol (TCP). Nonetheless, the catalyst retains appreciable turnover in such complex substrate mixtures. Taken together, the combination of substrate-specific selectivity and resilience to the total inhibition position Fe-MC6*a as a promising bioremediation catalyst for simultaneous halophenol detoxification in wastewater-treatment applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113154"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682809","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":"Synthesis and biological evaluation of Cu(II) Aroyl-Hydrazone Schiff Base complexes with anticancer activity against breast cancer cells","authors":"R. Margrate Thatcher ,&nbsp;Y. Manojkumar ,&nbsp;Rohith Ramasamy ,&nbsp;Buse Akturk ,&nbsp;Basak Dalbayrak ,&nbsp;Rajadurai Vijay Solomon ,&nbsp;Elif Damla Arısan ,&nbsp;V.Violet Dhayabaran","doi":"10.1016/j.jinorgbio.2025.113188","DOIUrl":"10.1016/j.jinorgbio.2025.113188","url":null,"abstract":"<div><div>Two novel Cu(II) Schiff base complexes were synthesized using aroyl-hydrazone ligands containing pyrrole (Complex 1) and furan (Complex 2) moieties and characterized through FTIR, UV–Vis, EPR, ESI-MS, and NMR spectroscopy, supported by DFT calculations. Spectroscopic and computational analyses confirmed square-planar geometry with coordination via azomethine nitrogen and phenolic oxygen atoms. Binding interactions with bovine serum albumin (BSA) and calf thymus DNA (CT-DNA) were investigated using UV–Vis and fluorescence spectroscopy, revealing stronger affinity for Complex 1 (K_b = 8.52 × 10⁵ M⁻¹) compared to Complex 2 (K_b = 1.06 × 10⁴ M⁻¹). Molecular docking and 100 ns molecular dynamics simulations indicating the stable binding conformations. Cytotoxicity studies against human breast cancer cell lines (MDA-MB-231 and MCF-7) showed that Complex 2 exhibited higher potency (IC₅₀ = 26.91 μM and 41.30 μM, respectively) than Complex 1. ROS and DAPI staining assays demonstrated apoptosis induction by Complex 2 through redox modulation and sub-G1 cell cycle arrest, suggesting a ligand-driven, partially DNA-independent mechanism. This suggests a</div><div>non-canonical behaviour of action where ligand-driven redox modulation, rather than DNA intercalation, triggers cell death. These findings highlight the significant role of heterocyclic substitution (pyrrole vs. furan) in modulating the biological activity of Cu(II) Schiff base complexes and underscore their potential as redox-active anticancer agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113188"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773189","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":"Targeting non-canonical DNA with π-extended Schiff Base complexes of Zinc(II), Copper(II), and Nickel(II): Insights into G-Quadruplex binding modes","authors":"Luisa D'Anna,&nbsp;Silvia Lo Iacono,&nbsp;Laura Marretta,&nbsp;Simona Rubino,&nbsp;Antonio Palumbo Piccionello,&nbsp;Riccardo Bonsignore,&nbsp;Giampaolo Barone","doi":"10.1016/j.jinorgbio.2025.113160","DOIUrl":"10.1016/j.jinorgbio.2025.113160","url":null,"abstract":"<div><div>The selective recognition of G-quadruplex (G4) DNA structures by metal complexes holds considerable promise for anticancer drug development, particularly for targeting oncogene promoters and telomeric regions. Herein, we report the synthesis, structural characterization, and DNA-binding strength evaluation of a new series of transition metal complexes derived from a N₄ tetradentate naphthalene-bridged Schiff base ligand (<em>Naphthim</em>). The zinc(II), copper(II) and nickel(II) complexes were obtained via in situ or transmetallation protocols and characterized by NMR, HR-ESI-MS, and elemental analysis. Among them, the copper(II) complex, <strong>2</strong>, <strong>[CuNaphthim]</strong>^{<strong>2+</strong>}, exhibited the highest DNA-binding affinity and G4-stabilizing ability, as assessed by FRET-based DNA melting assays, UV–Vis absorption, and circular dichroism (CD) spectroscopy. Despite lacking cationic side chain substituents, <strong>2</strong> showed moderate stabilization of several G4 structures, with a preferential effect on the <em>cMyc</em> quadruplex. Comparative studies with the benchmark <strong>[CuPhenim]</strong>^{<strong>2+</strong>} complex revealed that π-extension of the ligand framework substantially enhances DNA-binding affinity and modulates selectivity.</div><div>UV–Vis and CD spectroscopy revealed clear differences in DNA-binding behavior between <strong>2</strong> and <strong>[CuPhenim]</strong>^{<strong>2+</strong>}, with compound <strong>2</strong> exhibiting stronger and more defined interactions across both G4 and duplex targets. These trends found support by molecular docking, which uncovered distinct binding modes depending on G4 topology and echoed the observed affinity profiles. These findings highlight the <em>Naphthim</em> scaffold as a promising modular platform for the design of G4-targeting metal complexes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113160"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733822","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 zinc (II) gentamicin metalloantibiotic with outstanding antimicrobial activity and reduced susceptibility to bacterial resistance mechanisms: Experimental and theoretical explorations","authors":"Ivana R. Scolari,&nbsp;Mario A. Quevedo,&nbsp;Paulina L. Páez,&nbsp;Gladys E. Granero","doi":"10.1016/j.jinorgbio.2025.113153","DOIUrl":"10.1016/j.jinorgbio.2025.113153","url":null,"abstract":"<div><div>This paper reports the development of a complex between the antibiotic gentamicin sulfate (GEN), consisting of four major congeners, and zinc ions (Zn(II)GEN complex). The composition of the complex aligns well with the proposed molecular formula [Zn^₂+(L)(3H₂O)(2SO₄²⁻]. The Zn(II)GEN complex significantly enhanced inhibitory and bactericidal activity against <em>S. aureus</em>, <em>E faecalis</em>, <em>P. aeruginosa</em>, and <em>E. coli</em>. Unlike gentamicin sulfate alone, the Zn(II)-GEN complex did not induce drug-resistant mutants. Molecular modeling predicted predominantly hexacoordinated complexes involving three contact points with gentamicin and three with water, which agreed with the spectroscopic studies. The complexes adopted a restricted conformation of gentamicin, resulting in its hydrophilic groups being excluded from the solvent, which is consistent with the higher permeability. Molecular Modeling studies of the Zn(II)GEN complex with 16S RNA revealed a restricted bioactive conformation with stable interactions with residues A1493, G1494, and U1495, a structural requirement for antimicrobial activity. Free energy of binding analyses show that the Zn(<em>II</em>)GEN complex had better pharmacodynamic properties than the pure compound. A favored bioactive conformation formed upon the complexation of gentamicin sulfate with Zn(II) increased the complex's potency against bacteria and allowed it to penetrate bacterial cells. The complex also reduces the likelihood of antimicrobial resistance. The strategy is a good starting point for research into combating bacteria.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113153"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600640","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":"Triple-action Pt(IV) prodrugs of cisplatin and oxaliplatin with indole propionate and 4-phenylbutyrate ligands as potent anticancer agents","authors":"Leila Tabrizi ,&nbsp;Alan M. Jones ,&nbsp;Isolda Romero-Canelon ,&nbsp;Andrea Erxleben","doi":"10.1016/j.jinorgbio.2025.113183","DOIUrl":"10.1016/j.jinorgbio.2025.113183","url":null,"abstract":"<div><div>The synthesis and biological activity of two new platinum(IV) derivatives of cisplatin and oxaliplatin with indole-3-propionate (IPA) and the histone deacetylase inhibitor 4-phenylbutyrate (PBA) in axial position are reported. <em>Cis,cis,trans</em>-[Pt(NH₃)₂Cl₂(IPA)(PBA)] (<strong>1</strong>) and <em>tran</em>s-[Pt(DACH)(OX)(IPA)(PBA)] (<strong>2</strong>) (DACH = (1<em>R</em>,2<em>R</em>)-1,2-cyclohexanediamine; OX = oxalate) were characterized by elemental analysis, ESI-MS, FT-IR, and ¹H, ¹³C{¹H}, and ¹⁹⁵Pt{¹H} NMR spectroscopy. The cytotoxicity of the Pt(IV) complexes was evaluated in A2780 ovarian, A549 lung, PEA1 ovarian, SKOV3 ovarian, PC3 prostate and HCT116 colon cancer cells. Complex <strong>2</strong> is about 100 times more potent than cisplatin and about 30 times more potent than oxaliplatin in HCT116 cells. In contrast to cisplatin and oxaliplatin, <strong>1</strong> and <strong>2</strong> maintain their activity in HCT116 p53-knockout cells. Mechanistic studies indicated a multifactorial mechanism that includes histone deacetylase inhibition, the generation of reactive oxygen species and the disruption of mitochondrial function. The complexes affect the cell cycle and induce apoptotic cell death.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"276 ","pages":"Article 113183"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733866","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}