Journal of Inorganic Biochemistry最新文献

{"title":"Tuning the photoactivity of diazido Pt(IV) prodrugs with amino acid methyl esters","authors":"Huayun Shi ,&nbsp;Peter J. Sadler","doi":"10.1016/j.jinorgbio.2025.113021","DOIUrl":"10.1016/j.jinorgbio.2025.113021","url":null,"abstract":"<div><div>Photoactive Pt(IV) complexes conjugated to amino acid methyl esters <em>trans</em>,<em>trans</em>,<em>trans</em>-[Pt(py)₂(N₃)₂(OH)(succinate-amino acid methyl ester)] (amino acid = L-leucine (<strong>1</strong>), glycine (<strong>2</strong>), L-tyrosine (<strong>3</strong>) and L-tryptophan (<strong>4</strong>)) have been synthesised and characterised. Complexes <strong>1</strong>–<strong>4</strong> showed high dark stability, but were activated upon irradiation with blue light to generate azidyl and hydroxyl radicals and Pt(II) species. Interestingly, conjugated tryptophan in <strong>4</strong> quenched the formation of azidyl and hydroxyl radicals and Pt-guanosine 5′-monphosphate adducts, while the amino acids in complexes <strong>1</strong>–<strong>3</strong> showed no significant effects on the formation of their photoproducts. Improved photocytotoxicity but lower dark cellular Pt accumulation in A2780 human ovarian cancer cells were observed for <strong>1</strong>–<strong>4</strong>, with 50 % inhibition of cell viability (IC₅₀) values of 1.4–7.0 μM) compared with the parent complex <strong>FM-190</strong> (<em>trans, trans, trans</em>-[Pt(py)₂(N₃)₂(OH)₂]). Significant enhancement in Pt accumulation for <strong>3</strong> and <strong>4</strong> after irradiation probably contributes to their promising photocytotoxicity, especially for the tryptophan-conjugated complex <strong>4</strong>.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113021"},"PeriodicalIF":3.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863665","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":"One single hydrogen bond guarantees conformational stability and activity in coproheme decarboxylase from Corynebacterium diphtheriae","authors":"Gaurav Patil ,&nbsp;Peter Frasko ,&nbsp;Bettina Lier ,&nbsp;Thomas Gabler ,&nbsp;Paul G. Furtmüller ,&nbsp;Chris Oostenbrink ,&nbsp;Stefan Hofbauer","doi":"10.1016/j.jinorgbio.2025.113022","DOIUrl":"10.1016/j.jinorgbio.2025.113022","url":null,"abstract":"<div><div>Active site architectures of enzymes are defined by many interactions between substrate and amino acid residues and are optimized for specific and efficient substrate turnover. In the case of coproheme decarboxylase (ChdC) the active site architecture is well described by structural and thermodynamic means. Coproheme decarboxylases transform iron coproporphyrin III (coproheme) into iron protoporphyrin IX (heme <em>b</em>) by oxidatively decarboxylating two propionate groups to vinyls. In this study we have investigated an arginine residue (R208, ChdC from <em>Corynebacterium diphtheriae</em>) in close proximity to propionate at position 2 (p2) that has been indicated to have an important steric role within the active site architecture. Here we focus on the molecular basis of its steric role and the catalytic consequences by investigating several R208 variants of coproheme decarboxylase from the Actinobacterium <em>Corynebacterium dipht</em><em>h</em><em>eriae</em>. Analyses of the exchange of R208 into His, Lys, Glu, Asp, and Ser (serine mimics the situation of ChdCs in Firmicutes) help to deepen our understanding of this enzyme and its reaction mechanism. By employing experimental biochemical studies and molecular dynamics simulations we identify one single hydrogen bond of particular importance, proving that the protonation state matters and that R208 is an essential residue without having a direct mechanistic role during catalytic turnover.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113022"},"PeriodicalIF":3.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829825","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":"Exploring the fascination of metal-sulfur bonds, vivid colors, and electron transfer through proteins: A tribute to Harry B. Gray","authors":"Peter M.H. Kroneck","doi":"10.1016/j.jinorgbio.2025.113025","DOIUrl":"10.1016/j.jinorgbio.2025.113025","url":null,"abstract":"<div><div>The study of transition metals and their role in living matter has a long and distinguished history. This field, today referred to as Bioinorganic Chemistry, has evolved into a vibrant area of research. Progress is fueled by four main factors: (1) the use of high-tech spectroscopy to explore the structural and dynamic properties of molecules, (2) the molecular engineering and design of artificial enzymes, (3) the rapid determination of high-resolution structures of proteins and large protein complexes, and (4) the significant advancements in computational chemistry. First, I will take the reader on a brief journey “Meeting Harry B. Gray”. Hereafter, significant basic work in the laboratory and crucial key findings will be presented that have enhanced our understanding of the structural and functional features of notable metalloenzymes with unique catalytic sites: (i) the blue type-1 Cu center and the trinuclear O₂ activating Cu cluster in ascorbate oxidase, (ii) the purple mixed-valent [Cu^1.5+(CyS⁻)₂Cu^1.5+] copperA electron transfer center in nitrous oxide reductase and cytochrome <em>c</em> oxidase, (iii) intraprotein control of electron transfer rates by allosteric interactions within the green nitrite reductase cytochrome <em>cd</em>₁, and (iv) active site structure and reaction mechanism of the red pentaheme cytochrome <em>c</em> nitrite reductase based on crystallographic identification of reaction intermediates and density functional calculations. This topic is particularly apt for honoring Harry B. Gray, who has made numerous seminal contributions to modern Inorganic Chemistry, especially as we celebrate his 90th birthday.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113025"},"PeriodicalIF":3.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842409","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":"Indium(III) 8-hydroxyquinolinates: Activity and selectivity towards multi-drug resistant strains of Klebsiella pneumoniae","authors":"Charles R.M. Soukup ,&nbsp;Rebekah N. Duffin ,&nbsp;Laurence Meagher ,&nbsp;Philip C. Andrews","doi":"10.1016/j.jinorgbio.2025.113024","DOIUrl":"10.1016/j.jinorgbio.2025.113024","url":null,"abstract":"<div><div>A series of dimethyl indium(III) 8-hydroxyquinolinates; [InMe₂(Q\")] (<strong>1</strong>), [InMe₂(Q'Cl)] (<strong>2</strong>), [InMe₂(QCl₂)] (<strong>3</strong>), [InMe₂(QBr₂)] (<strong>4</strong>), [InMe₂(QI₂)] (<strong>5</strong>), [InMe₂(QICl)] (<strong>6</strong>), and a series of indium(III) <em>tris</em>(8-hydroxyquinolinates); [In(Q\")₃]•H₂O (<strong>7</strong>), [In(QCl₂)₃] (<strong>8</strong>), [In(QBr₂)₃] (<strong>9</strong>), [In(QI₂)₃] (<strong>10</strong>), and [In(QICl)₃] (<strong>11</strong>), (where Q\"-<em>H</em> = C₉H₇NO; Q'Cl-<em>H</em> = C₉H₆NOCl, QCl₂-<em>H</em> = C₉H₅NOCl₂; QBr₂-<em>H</em> = C₉H₅NOBr₂; QI₂-<em>H</em> = C₉H₅NOI₂; and QICl-<em>H</em> = C₉H₅NOICl) were synthesised, characterised, and evaluated for their antibacterial activity against Gram-positive bacteria (vancomycin-resistant <em>E. faecalis</em>, <em>S. aureus</em>, methicillin-resistant <em>S. aureus</em>), Gram-negative bacteria (<em>K. pneumoniae</em>, <em>A. baumannii</em>, <em>P. aeruginosa</em>, and <em>E. coli</em>) and mammalian cell inhibition of L929 fibroblasts. Single crystal X-ray diffraction data of <strong>2–4</strong> indicates the dimethylindium complexes are dimeric in the solid-state through ‘In₂O₂’ bridging. Complexes <strong>1–6</strong> exhibit significant activity and selectivity against three multi-drug resistant strains of <em>K. pneumoniae</em>, with MIC (minimum inhibitory concentration) values as low as 49 nM and selectivity indices as high as 159 against carbapenem-resistant strain RH201207. The antibacterial activity and selectivity against <em>K. pneumoniae</em> is generally enhanced upon complexation of the 8-hydroxyquinolinate ligands to indium(III).</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113024"},"PeriodicalIF":3.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902737","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":"Mechanisms of bacterial heme uptake and degradation: Diverse strategies for ring opening","authors":"Kieran Johnson,&nbsp;Fengtian Xue,&nbsp;Angela Wilks","doi":"10.1016/j.jinorgbio.2025.113023","DOIUrl":"10.1016/j.jinorgbio.2025.113023","url":null,"abstract":"<div><div>Iron acquisition by bacterial pathogens is critical for their survival and virulence within the host. Heme represents a viable source of iron by which pathogens overcome the limited iron availability and establish infection. Over the past decade several new paradigms in bacterial heme degradation have been identified. Herein, we will briefly discuss the mechanisms by which bacterial pathogens acquire and utilize heme with a particular focus on the three major classes of heme-degrading enzymes: the canonical heme oxygenases (HO), the non-canonical HOs, and the class C radical SAM methyl transferases. The canonical HO enzymes typified by the gram-negative pathogens <em>Pseudomonas aeruginosa</em> and <em>Neisseriae meningitidis</em> were shown to be structurally and mechanistically similar to the eukaryotic HO enzymes. In contrast, the non-canonical HOs of the gram-positive pathogen <em>Staphylococcus aureus</em> and <em>Mycobacterium tuberculosis</em> have a distinct ferredoxin-like structural fold and extreme heme ruffling that gives rise to alternate heme metabolites. Enteric pathogens such as <em>E. coli</em> O157:H7 and <em>Vibrio cholera</em> encode a heme-dependent radical SAM methyl transferase that opens the porphyrin ring in an oxygen-independent manner essential in the anoxic environment of the gut. All three classes of heme-degrading enzymes provide an advantage for survival within the host, while also yielding metabolites that play a role in bacterial adaptation and virulence. Therefore, a complete understanding of the distinct mechanisms of heme degradation and the role of the unique heme metabolites will provide a platform for the development of antibacterial strategies targeting heme catabolism.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113023"},"PeriodicalIF":3.2,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829836","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":"DFT investigation of metal coordination and reactivity in minimal metalloenzyme models","authors":"Rajeev Kumar ,&nbsp;Youngsuk Kim ,&nbsp;Jeong-Mo Choi","doi":"10.1016/j.jinorgbio.2025.113018","DOIUrl":"10.1016/j.jinorgbio.2025.113018","url":null,"abstract":"<div><div>Metalloenzymes achieve catalytic functionality by precisely controlling their metal coordination environments through structural constraints. However, the influence of structural rigidity on metal substitution and its impact on enzyme structure and reactivity has not been fully elucidated. To address this, we investigated how structural constraints affect metal coordination geometry, energetics, and reactivity within the active site of human carbonic anhydrase II (CA II) using DFT. We constructed semi-constrained models of metal substituted CA II from their X-ray crystal structures containing Zn²⁺ (native), Cu²⁺, Ni²⁺, and Co²⁺. Semi-constrained models were constructed to mimic the microenvironment of the protein active site, and multiple DFT methods were benchmarked to identify an accurate and efficient computational approach. Structural constraints lead to a rugged energy landscape with multiple local minima, and we found that upon metal substitutions, the competition between the structural constraints and the intrinsic coordination chemistry leads to diverse consequences in final geometry. We also found that the native metal ion (Zn²⁺) in metalloenzymes CA II does not always exhibit the strongest binding among the metal ions tested; instead, the trends follow the Irving-Williams series. However, electrophilicity analysis revealed that constrained geometries modulate the electronic reactivity of the metal center, with Zn²⁺ consistently exhibiting the highest electrophilicity, and this explains the evolutionary optimization of the metalloenzyme. These findings enhance our understanding of metal coordination under structural constraints and provide a computational basis for exploring metal substitutions in artificial metalloenzymes.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113018"},"PeriodicalIF":3.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757910","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":"Indeno[1,2-b]-quinoline carboxylic acids and their dimethylgallium(III) complexes: Evaluation of their efficacy as antibacterial agents","authors":"Sumiyyah Hameed,&nbsp;Kirralee J. Burke,&nbsp;Rebekah N. Duffin,&nbsp;Victoria L. Blair,&nbsp;Philip C. Andrews","doi":"10.1016/j.jinorgbio.2025.113017","DOIUrl":"10.1016/j.jinorgbio.2025.113017","url":null,"abstract":"<div><div>In seeking to meet the ongoing challenge of antimicrobial resistance through novel metallo-based strategies, a series of five indeno[1,2-<em>b</em>]-quinoline carboxylic acids (= RQ<em>H</em>; where R is H {not shown}, F, Cl, Br, I and CH₃) and their respective organogallium(III) complexes [GaMe₂(Q)(H₂O)] <strong>1</strong>, [GaMe₂(FQ)(H₂O)] <strong>2</strong>, [GaMe₂(BrQ)(H₂O)] <strong>3</strong>, [GaMe₂(ClQ)(H₂O)] <strong>4</strong>, and [GaMe₂(CH₃Q)(H₂O)] <strong>5</strong>, have been synthesised, fully characterised, and their antibacterial activity and mammalian cell toxicity studied. Crystallisation from ethanol allowed determination of the solid-state structures of [GaMe₂(Q)(H₂O)] <strong>1</strong> and [{GaMe₂(CH₃Q)}₂(H₂O)(EtOH)]·H₂O <strong>5 A</strong> through single crystal X-ray diffraction. The hydrolytic stability of the dimethylgallium(III) complexes was assessed in the biological vehicle solvent DMSO doped with 10 % D₂O. All remained intact in the aqueous environment, indicating a high degree of hydrolytic stability. Complexes <strong>1</strong>–<strong>5</strong> were evaluated as antibacterial agents towards antibiotic-resistant strains of <em>Klebsiella pneumoniae</em>, KP-1074, KP-AJ289, and KP-RH201207 using a broth microdilution assay. In high iron concentration media (Luria-Bertani broth), conventionally used to grow bacteria, all complexes and the free indenoquinoline carboxylic acids were inactive. When analysed in a low iron medium (RPMI-1640 supplemented with 10 % human serum) however, the complexes were observed to exert antibacterial activity as low as 90 nM (range: 0.09–1.56 μM), whilst the free indenoquinoline carboxylic acids remained inactive.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"273 ","pages":"Article 113017"},"PeriodicalIF":3.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809558","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":"Activating metal sites for electron transfer and catalysis","authors":"Edward I. Solomon ,&nbsp;Robert R. Gipson","doi":"10.1016/j.jinorgbio.2025.113009","DOIUrl":"10.1016/j.jinorgbio.2025.113009","url":null,"abstract":"<div><div>This Focused Review is based on a brief presentation by Ed Solomon at a celebration of Harry Gray’s 90th birthday at Northwestern University on May 3, 2025. This review focuses on areas of Ed’s research on electron transfer and catalysis strongly influenced by Harry’s early science.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113009"},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738029","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 anticancer evaluation of tri-n-butyltin complexes featuring azomethine- and diazenyl-functionalized benzoates with peripheral fluorine against MDA-MB-231 breast cancer cells","authors":"Tushar S. Basu Baul ,&nbsp;Amon Das ,&nbsp;Avishek Khatiwara ,&nbsp;Vivek Kumar Sharma ,&nbsp;Andrew Duthie ,&nbsp;Biplob Koch ,&nbsp;Sean Parkin","doi":"10.1016/j.jinorgbio.2025.113013","DOIUrl":"10.1016/j.jinorgbio.2025.113013","url":null,"abstract":"<div><div>Five complexes, [<em>n</em>-Bu₃Sn(HL^H)] (<strong>1</strong>), [<em>n</em>-Bu₃Sn(HL^4-F)] (<strong>2</strong>), [<em>n</em>-Bu₃Sn(HL^{2<strong>-CF3</strong>})] (<strong>3</strong>), [<em>n</em>-Bu₃Sn(HL^{3<strong>-</strong>CF3})] (<strong>4</strong>) and [<em>n</em>-Bu₃Sn(HL^{4<strong>-</strong>CF3})] (<strong>5</strong>), were synthesized by reacting the corresponding azomethine- and diazenyl-functionalized hydroxy-benzoic acid pro-ligands (H'HL^H, H'HL^4-F, H'HL^2-CF3, H'HL^3-CF3 and H'HL^4-CF3) with (<em>n</em>-Bu₃Sn)₂O. Compounds <strong>1</strong>–<strong>5</strong> were thoroughly characterized by FT-IR and NMR (¹H, ¹³C, and ¹¹⁹Sn) spectroscopy. Additionally, the molecular and crystal structures of compounds <strong>2</strong>, <strong>4</strong> and <strong>5</strong>, along with one of their pro-ligands (H'HL^3-CF3), were determined by single-crystal X-ray diffraction analysis. The tri-<em>n</em>-butyltin(IV) complexes (<strong>2</strong>, <strong>4</strong>, and <strong>5</strong>) form mono-periodic chains in which the <em>n</em>-Bu₃Sn groups are linked to the oxygen atoms of the benzoate ligand through one short and one long Sn-O bond. This arrangement results in a pentacoordinated tin center, exhibiting slightly distorted <em>trans</em>-Bu₃SnO₂ trigonal-bipyramidal geometries, as indicated by their τ₅ parameters. The hydroxy H atom forms an intramolecular O–H···N hydrogen bond with the imine N-atom, as observed in the crystal structure of H'HL^3-CF3. The ¹¹⁹Sn NMR spectra of compounds <strong>1</strong>–<strong>5</strong> showed a resonance at around +110 ppm, consistent with a tetrahedral geometry in solution. This suggests that the polymeric structures of complexes <strong>2</strong>, <strong>4</strong>, and <strong>5</strong> observed in the solid state dissociate upon dissolution. The <em>in vitro</em> cytotoxicity of the tri-<em>n</em>-butyl compounds <strong>1</strong>–<strong>5</strong> was assessed against MDA-MB-231 breast cancer cells. Compounds <strong>1</strong>–<strong>5</strong> showed potent cytotoxicity against MDA-MB-231 cells (IC₅₀: 0.90–2.18 μM), with the fluorinated complex [<em>n</em>-Bu₃Sn(HL^4-F)] (<strong>2</strong>) being the most active (IC₅₀ = 0.90 ± 0.05 μM). The proposed mechanism of action is discussed in light of findings from various biological assays.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113013"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738027","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":"Novel zinc(II) complexes bearing N,N,N-tridentate pyrimidine ligands as antitumor agents: Synthesis, characterization and antitumor evaluation","authors":"Jing Wang ,&nbsp;Bin Zhang ,&nbsp;Huan-Huan Yang ,&nbsp;Jia-Xing Lu ,&nbsp;Ao Shen ,&nbsp;Jun-Ying Song ,&nbsp;Juan Yuan ,&nbsp;Zhen-Qiang Zhang","doi":"10.1016/j.jinorgbio.2025.113016","DOIUrl":"10.1016/j.jinorgbio.2025.113016","url":null,"abstract":"<div><div>Herein, a series of Zn(II) complexes (<strong>1</strong>–<strong>4</strong>) with a six-coordinate octahedral configuration were successfully designed and synthesized using pyrimidine-pyridine derivatives HL¹-HL⁴. The structures of complexes <strong>1</strong>–<strong>4</strong> were systematically characterized by ¹H NMR, IR, UV–Vis, X-ray single-crystal diffraction and XRD. MTT assays using selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) demonstrated that complexes <strong>1</strong>–<strong>4</strong> exhibited superior anti-proliferative activity compared to their corresponding ligands HL¹-HL⁴ and the conventional chemotherapeutic agent cisplatin. Notably, complexes <strong>1</strong>–<strong>4</strong> showed particularly potent anti-proliferative effects against BGC-823 cells, with IC₅₀ values ranging from 3.22 to 5.73 μM. Importantly, complexes <strong>1</strong>–<strong>4</strong> displayed significantly lower cytotoxicity toward normal human HL-7702 cells than cisplatin. Based on these findings, complexes <strong>1</strong> and <strong>4</strong>, which exhibited the most potent activity against BGC - 823 cells, were selected for further investigation of their apoptosis - inducing mechanisms using Annexin <em>V</em> - FITC/PI double staining, AO/EB double staining, ROS fluorescence intensity detection, mitochondrial membrane potential assessment methods and the Western blot (WB).The results indicated that complexes <strong>1</strong> and <strong>4</strong> effectively suppressed tumor cell proliferation by triggering apoptosis, potentially via processes related to the production of reactive oxygen species (ROS) and mitochondrial impairment. Furthermore, the WB results indicate that complexes <strong>1</strong> and <strong>4</strong> induce tumor cell apoptosis by inhibiting Bcl-2 protein expression and promoting the generation of cleaved caspase-3. In summary, complexes <strong>1</strong>–<strong>4</strong> exhibit significant promise for the creation of antitumor therapies, providing a novel direction for further investigation and application in tumor treatment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113016"},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714173","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}