Journal of Inorganic Biochemistry最新文献

{"title":"A molecular basis of Ferredoxin Reductase (FdxR) mutations that result in mitochondriopathies","authors":"Amit Kumar,&nbsp;Janie E. McGlohon,&nbsp;D. Fernando Estrada","doi":"10.1016/j.jinorgbio.2025.112969","DOIUrl":"10.1016/j.jinorgbio.2025.112969","url":null,"abstract":"<div><div>Inherited mutations in the Ferredoxin Reductase (FdxR) gene can result in a spectrum of disorders that include auditory and optic neural atrophies as well as adrenal insufficiency. FdxR (also referred to as Adrenodoxin Reductase) is a flavoprotein located in the inner mitochondrial membrane. It is responsible for mediating electron transfer from NADPH to either Fdx1 (Adrenodoxin), which is the sole reductant for all seven mitochondrial cytochromes P450, or to the related ferredoxin Fdx2, which is a component in the Fe<img>S cluster biogenesis pathway. In most cases, the mechanistic causes that underpin FdxR-related neuropathies and steroid imbalances remain unknown. In this study, we investigate three clinically relevant variants of FdxR (R211Q, R275C, and R355Q) that exhibit classic FdxR-related disease phenotypes and are widely distributed in the protein. We use a combination of biophysical and biochemical techniques to evaluate both the FdxR:Fdx1 complex and the FdxR:Fdx2 complex since these redox complexes represent an important branch point in FdxR function. Two key findings from this study are that i) all three mutants alter the recognition of Fdx1 and Fdx2, despite R275C and R355Q being located distally from the expected site of interaction, and ii) R275C and R355Q disrupt the functional complex with Fdx1, but not with Fdx2. These findings are supplemented with 2D NMR data of each mutant FdxR complex. In summary, this work implicates protein instability and degradation as the proximal cause of FdxR-related disease, with a secondary cause being the disruption of cytochrome P450-mediated metabolism in mitochondria.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"271 ","pages":"Article 112969"},"PeriodicalIF":3.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222038","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-function relationship within helical peptoids for Cu2+ chelation in the context of Alzheimer's disease","authors":"Anastasia E. Behar,&nbsp;Galia Maayan","doi":"10.1016/j.jinorgbio.2025.112961","DOIUrl":"10.1016/j.jinorgbio.2025.112961","url":null,"abstract":"<div><div>Peptoids (N-substituted glycine oligomers) represent an excellent platform for drug development, such as selective chelators for Cu²⁺ ions towards chelation therapy, due to their efficient synthesis, high stability and good bioavailability. We previously showed that peptoids helicity is essential for selective Cu²⁺ binding and identified a unique peptoid hexamer, having 2,2′:6′,2″-terpyridine, and 8-hydroxyquinoline as metal-binding sidechains facing the same side of the helix, which exhibits high selectivity to Cu²⁺ ions. However, maintaining a stable helix required the incorporation of bulky chiral sidechains, resulting in a hydrophobic peptoid, insoluble in aqueous solutions, and limited in its use as a drug candidate. Our attempts to solubilize this peptoid led to the discovery of a water-soluble sequence able to selectively extract Cu²⁺ from Cu-amyloid complex, and by this stop the formation of reactive oxygen species (ROS) in the context of Alzheimer's disease (AD). This peptoid, however, had limited solubility in buffer solutions (that mimic biological environment), thus its potential for further development as a therapeutic for AD was limited. In this current study, we explore the structure-function relationship within a newly synthesized set of helical and water-soluble peptoids. By extensive spectroscopic analysis we test the effect of helix stability as well as the type and number of the solubilizing group(s) and their position along the sequence, on the solubility of these peptoids in buffer, and on their selectivity for Cu and ability to inhibit ROS production. The results provide insights about the relationships between the structure of the peptoids/Cu-peptoids and ROS production inhibition.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"271 ","pages":"Article 112961"},"PeriodicalIF":3.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205116","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 mitochondria-targeting rutheniumII and iridiumIII anticancer complexes containing hybrid N^NH-chelated ligands","authors":"Heqian Dong,&nbsp;Hanxiu Fu,&nbsp;Kangning Lai,&nbsp;Zhihao Yang,&nbsp;Shuli Wang,&nbsp;Qiuyi Lv,&nbsp;Zhe Liu,&nbsp;Lihua Guo","doi":"10.1016/j.jinorgbio.2025.112960","DOIUrl":"10.1016/j.jinorgbio.2025.112960","url":null,"abstract":"<div><div>A series of half-sandwich ruthenium^II and iridium^III complexes bearing hybrid sp³-N/sp²-N amine-imine bidentate chelating ligands were strategically designed and synthesized. Their structures were fully characterized by ¹H and ¹³C NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction, revealing nonplanar five-membered metallacycles in representative complexes. The complexes exhibited potent cytotoxicity against A549 lung, HeLa cervical, and HepG2 liver cancer cell lines, with IC₅₀ values ranging from 0.88 to 4.98 μM, significantly lower than that of cisplatin. Notably, the amine-imine complexes displayed superior cytotoxicity compared to their α-diimine analogues. Mechanistic studies indicated that DNA binding is not the primary mode of action. Instead, these complexes selectively target mitochondria, induce mitochondrial membrane depolarization, elevate intracellular reactive oxygen species (ROS) levels, and trigger apoptosis. Additionally, they enter A549 cells through an energy-dependent pathway and effectively inhibit cancer cell migration in vitro.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"271 ","pages":"Article 112960"},"PeriodicalIF":3.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189333","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 studies of Ru/Ir arene complexes bearing oleanolic acid in acute promyelocytic leukemia cells","authors":"Xiang-Yu Dai ,&nbsp;Zheng-Qi Shen ,&nbsp;Yating Zhang,&nbsp;Hanxue Liu,&nbsp;Meng Ren,&nbsp;Peisen Wang,&nbsp;Ji Li,&nbsp;Xuling Xue,&nbsp;Hong-Ke Liu","doi":"10.1016/j.jinorgbio.2025.112959","DOIUrl":"10.1016/j.jinorgbio.2025.112959","url":null,"abstract":"<div><div>Acute leukemia, a cancer originating in the bone marrow and blood-forming tissues, poses a significant threat to human health. Chemotherapy may cause a range of side effects and further cause greater suffering to the patients. Thus, reducing the toxicity of the drugs for treating leukemia has become a significant challenge. In this study, we developed two non‑platinum anticancer agents, <strong>ole-Ru</strong> and <strong>ole-Ir</strong>, by fusing the natural product oleanolic acid as the ligand into two metal (ruthenium and iridium) precursors. <strong>Ole-Ru</strong> and <strong>ole-Ir</strong> not only exhibited remarkable selectivity and cytotoxicity against NB4 cells through the apoptosis pathway, but also demonstrated low toxicity towards normal lung fibroblast cells, suggesting their potential for targeted treatment of acute leukemia cells. This work presents a rational design strategy for metal-based anticancer complexes aimed at inhibiting NB4 cells and expanded the scope of metallodrugs used in the treatment of leukemia.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"271 ","pages":"Article 112959"},"PeriodicalIF":3.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168068","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 chemistry of H2DEDPA derivatives for [nat/68Ga]Ga3+ complexation","authors":"Daniel Torralba-Maldonado ,&nbsp;Axia Marlin ,&nbsp;Phuong Nguyen Tran ,&nbsp;Jennifer N. Whetter ,&nbsp;Fátima Lucio-Martínez ,&nbsp;Isabel Brandariz ,&nbsp;Paulo Pérez-Lourido ,&nbsp;Rosa M. Ortuño ,&nbsp;Eszter Boros ,&nbsp;Ona Illa ,&nbsp;David Esteban-Gómez ,&nbsp;Carlos Platas Iglesias","doi":"10.1016/j.jinorgbio.2025.112946","DOIUrl":"10.1016/j.jinorgbio.2025.112946","url":null,"abstract":"<div><div>We report a detailed study of the coordination chemistry of acyclic hexadentate H₂DEDPA derivatives towards [^nat/68Ga]Ga³⁺ (H₂DEDPA = 6,6′-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid). Three structural modifications were considered, involving the substitution of the central ethylene spacer of H₂DEDPA by 1,2-cyclohexyldiamine, 1,2-cyclopentyldiamine or 1,3-cyclobutyldiamine linkers, affording chelators H₂CHXDEDPA, H₂CpDEDPA and H₂CBuDEDPA, respectively. The X-ray structures of [Ga(CpDEDPA)](PF₆)·3H₂O and [Ga(CBuDEDPA)](ClO₄)·H₂O evidence hexadentate binding of the ligands to Ga³⁺, which displays a distorted octahedral coordination environment. Solution structures compare well to those observed in the solid state, as demonstrated by NMR studies and DFT calculations. The stability constants of the complexes were determined using spectrophotometric titrations (25 °C, 1 M NaCl), affording log <em>K</em>_GaL values of 24.94, 21.90 and 19.50 for the complexes of CHXDEDPA²⁻, CpDEDPA²⁻ and CBuDEDPA²⁻, respectively. Both CHXDEDPA²⁻ and CpDEDPA²⁻ can be quantitatively radiolabeled with 10 nmol [⁶⁸Ga]Ga³⁺ at room temperature (0.5 M ammonium acetate at pH 5) with no significant difference between 15, 30 and 60 min labeling time, whereas CBuDEDPA²⁻ produced a &lt; 50 % radiochemical yield. The radiolabeled complexes of CHXDEDPA²⁻ and CpDEDPA²⁻ showed high stability in PBS buffer and in the presence of 1000 equivalents of DTPA⁵⁻, with CpDEDPA²⁻ providing slightly better results. However, in vivo PET imaging and biodistribution studies evidence dissociation of the CpDEDPA²⁻ complex, while the [⁶⁸Ga][Ga(CHXDEDPA)]⁺ complex remains stable and demonstrates mixed, renal and hepatic clearance.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"271 ","pages":"Article 112946"},"PeriodicalIF":3.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147567","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 zinc phthalocyanine-based photosensitizer for photodynamic therapy: Photophysical, theoretical and in vitro studies","authors":"Özge Özten ,&nbsp;Cansu Adkuvayçin ,&nbsp;Ceren Can Karanlık ,&nbsp;Fernando Aguilar-Galindo ,&nbsp;Mustafa Zahid Yıldız ,&nbsp;Lukasz Sobotta ,&nbsp;Ali Erdoğmuş ,&nbsp;Emre Güzel","doi":"10.1016/j.jinorgbio.2025.112958","DOIUrl":"10.1016/j.jinorgbio.2025.112958","url":null,"abstract":"<div><div>The preparation of new photosensitizers and studies on photodynamic therapy (PDT) have provided promising results and realistic expectations for an efficient medical treatment. Phthalocyanines (Pcs) have become extremely attractive for this purpose owing to their molecular versatility and superior physicochemical properties. Motivated by these facts, in this study, non-peripherally substituted zinc(II) Pc (<strong>2</strong>) was prepared by cyclotetramerization of the phthalonitrile derivative bearing 3-methoxybenzyloxy units. Also, physicochemical and <em>in vitro</em> analyses were completed. In photochemical studies, the obtained singlet oxygen quantum yield (Φ_Δ) values were 0.73 in dimethylsulphoxide (DMSO) and 0.55 in dimethylformamide (DMF). Theoretical calculations based on density functional theory (DFT) provide valuable information on the energies and character of the electronic excitations, thus allowing a prediction of their potential applicability to generate singlet oxygen. The PDT activity of the zinc(II) phthalocyanine bearing 3-methoxybenzyloxy substituents was tested <em>via in vitro</em> studies using the human colon cancer cell lines. In cytotoxicity experiments, the most effective incubation time for cell lines was found to be 24 h, and the most effective concentration was 8 μM. Furthermore, the cell viability rate decreased significantly with the increasing power density. The results suggested that the newly synthesized zinc(II) Pc is an effective photosensitizer with potential use for the treatment of colon cancer.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112958"},"PeriodicalIF":3.8,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107562","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":"Gold(I) complexes with NHC ligands functionalized with sulfoxide groups: Design, synthesis, in vitro studies and insights into the mechanism of action as anticancer drugs","authors":"Eleonora Zampieri ,&nbsp;Chiara Donati ,&nbsp;Victoria Mechrouk ,&nbsp;Thierry Achard ,&nbsp;Stéphane Bellemin-Laponnaz ,&nbsp;Alessandro Dolmella ,&nbsp;Cristina Marzano ,&nbsp;Marco Baron ,&nbsp;Valentina Gandin ,&nbsp;Cristina Tubaro","doi":"10.1016/j.jinorgbio.2025.112957","DOIUrl":"10.1016/j.jinorgbio.2025.112957","url":null,"abstract":"<div><div>Mononuclear silver(I) complexes of the type [AgBr(NHC)] (NHC=<em>N</em>-heterocyclic carbene) were prepared by reaction of the imidazolium salt NHC·HBr with Ag₂O. The corresponding gold(I) complexes [AuCl(NHC)] were isolated by transmetalation reaction from the silver complex to the [AuCl(SMe₂)] precursor. The employed NHC ligands are characterized by benzyl and CH₂CH₂S(O)R (R = Ph or <em>t</em>-Bu) groups as nitrogen wingtip substituents. The antiproliferative activity of the Ag(I) and Au(I) complexes on a panel of different human cancer cell lines is reported. The results show that gold(I) complexes are more active than the analogous silver(I) ones, and between the two gold(I) complexes, the one with R = Ph displays the best results, with IC₅₀ values ranging from 5.4 to 30.6 μM. Mechanistic studies confirm the ability of the reported complexes to hamper Thioredoxin Reductase (TrxR) activity and cellular redox homeostasis, thus leading to oxidative stress induction.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"271 ","pages":"Article 112957"},"PeriodicalIF":3.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167792","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":"Decoding the prospective of metal complexes in anti-cancer therapeutics by targeting of G-quadruplex DNA","authors":"Pulakesh Pramanik ,&nbsp;Santanu Bhattacharya","doi":"10.1016/j.jinorgbio.2025.112947","DOIUrl":"10.1016/j.jinorgbio.2025.112947","url":null,"abstract":"<div><div>The use of metallodrugs in cancer therapy received widespread interest after the successful application of cisplatin and its analogous compounds as chemotherapeutic medications. Despite the development of various metallodrugs in past years, platinum-based chemotherapeutic agents are the only clinically approved metallodrugs that primarily interact with genomic DNA and trigger severe dose-limiting adverse side effects in cancer patients. As a consequence, the advancement of new risk-free metallodrugs has become a topmost concern in cancer research to minimize toxicity and improve therapeutic outcomes. G-quadruplex (G4) DNA structures have recently come to light as an attractive drug target in cancer therapy because of their gene regulation ability and role in maintaining genomic stability. Their presence in telomere and promoter region of oncogenes has the potential to induce apoptosis in cancer cells through the inhibition of telomerase activity and gene expression. Therefore, the development of new G4 DNA targeting small molecular entities including metal complexes came out as a viable approach for uprooting cancer disease. Beyond organic small molecules, innumerable metal complexes have been developed in past years to target G4 DNA structures in the context of cancer therapy. This review primarily aims to highlight these metal complexes through a comprehensive discussion about their structural properties, their binding interactions with G4 DNA, their cancer cell growth inhibition mechanisms, and their efficacy in both cellular and in vivo systems, to decode their potential as anti-cancer drugs. Additionally, the potential of these metal complexes in the field of bio-imaging and photodynamic therapy is also explored.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112947"},"PeriodicalIF":3.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116254","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":"Anti-tumor and cellular mechanisms of HfIV tetra-(8-hydroxyquinolinato) complexes","authors":"Tiankun Zhao ,&nbsp;Dongyu Mei ,&nbsp;Jing Ma ,&nbsp;Nan Liu ,&nbsp;Qi Zhang ,&nbsp;Zhongduo Yang ,&nbsp;Isabel Correia","doi":"10.1016/j.jinorgbio.2025.112945","DOIUrl":"10.1016/j.jinorgbio.2025.112945","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Three 8-hydroxyquinoline-stabilized hafnium complexes, &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(oxinate)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt;, were synthesized with good aqueous stability and solubility by reacting Hf&lt;sup&gt;IV&lt;/sup&gt;Cl&lt;sub&gt;4&lt;/sub&gt; with 8-hydroxyquinoline (HL&lt;sub&gt;1&lt;/sub&gt;), 2-methyl-8-hydroxyquinoline (HL&lt;sub&gt;2&lt;/sub&gt;) and 5-chloro-8-hydroxyquinoline (HL&lt;sub&gt;3&lt;/sub&gt;) in THF, achieving high yields. Among the synthesized complexes, &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; and &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;3&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; exhibited potent inhibitory activity against human liver (Hep G2), cervical (HeLa S3) and lung (PC9) cancer cell lines, while showing low toxicity against non-tumorigenic murine epithelial AML12 cells. Notably, &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; demonstrated the most potent activity, with an IC&lt;sub&gt;50&lt;/sub&gt; value of 0.8 ± 0.3 μM against Hep G2 cells, which is 17 times lower than that of cisplatin (IC&lt;sub&gt;50&lt;/sub&gt; = 13.8 ± 1.3 μM). Mechanistic cell studies revealed that &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; could effectively inhibit cell migration, induce reactive oxygen species generation and cause mitochondrial membrane potential disruption. Furthermore, &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; blocked the cell cycle progression at the G2/M phase and led almost exclusively to early apoptosis in Hep G2 cells. Western blot analysis revealed that in Hep G2 cells &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; could upregulate the expression of caspase-3 and Bax proteins while downregulating the expression of the anti-apoptotic Bcl-2 protein, highlighting the apoptotic pathway as a key mechanism of action. Comparisons are made with previously reported &lt;strong&gt;[Zr&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt;, which shows higher cytotoxicity, cellular uptake, reactive oxygen species generation, mitochondrial damage and stronger inhibition of antioxidant enzymes' activity. However, &lt;strong&gt;[Hf&lt;/strong&gt;&lt;sup&gt;&lt;strong&gt;IV&lt;/strong&gt;&lt;/sup&gt;&lt;strong&gt;(L&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;1&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;)&lt;/strong&gt;&lt;sub&gt;&lt;strong&gt;4&lt;/strong&gt;&lt;/sub&gt;&lt;strong&gt;]&lt;/strong&gt; induces prim","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112945"},"PeriodicalIF":3.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948697","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":"Formulation of naphthol-derived 1,2,3-triazole: A ‘turn-on’ chemosensor for Zr(IV) with anti-cancer and anti-bacterial activities","authors":"Gurjaspreet Singh ,&nbsp;Komal ,&nbsp;Anu Radha ,&nbsp;Harshbir Kaur ,&nbsp;Bhavana Rani ,&nbsp;Baljinder Singh Gill ,&nbsp;Deepanjali Baliyan ,&nbsp;Amarjit Kaur ,&nbsp;Brij Mohan","doi":"10.1016/j.jinorgbio.2025.112944","DOIUrl":"10.1016/j.jinorgbio.2025.112944","url":null,"abstract":"<div><div>On prolonged exposure, transition metals can have detrimental effects on the environment as well as humans. However, this led to the idea for the synthesis of a chemosensor for Zr(IV) detection which is a well-known hard transition metal. In this current article, we have synthesized Naphthol-derived 1,2,3-triazole (NPTZ) via click chemistry which was characterized with the help of (NMR, FT-IR) spectroscopy, TGA studies, and mass spectral analysis. The photophysical studies had shown a great chemosensitivity towards Zr(IV) with non-interference of other metal cations. In addition, NPTZ has efficient LOD values of 26 nM (absorption analysis) and 478.6 nM (emission analysis). The Stable coordination complex of NPTZ-Zr(IV) was synthesized with a stoichiometry of 1:1 by utilizing Job's plot approach. Moreover, the NPTZ also demonstrates notable biological significance, including substantial anti-cancer and anti-microbial properties. In order to this, Molecular docking was performed which showed a considerable docking score of binding energies −8.84 kcal/mol (PDB ID-2R3I) and − 7.73 kcal/mol (PDB ID–<span><span>4OZ5</span><svg><path></path></svg></span>) with high values of inhibition constants.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"270 ","pages":"Article 112944"},"PeriodicalIF":3.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068774","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}