Journal of Inorganic Biochemistry最新文献

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Novel zinc(II) complexes bearing N,N,N-tridentate pyrimidine ligands as antitumor agents: Synthesis, characterization and antitumor evaluation 新型含N,N,N三齿嘧啶配体的锌(II)配合物抗肿瘤:合成、表征及抗肿瘤评价
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-23 DOI: 10.1016/j.jinorgbio.2025.113016
Jing Wang , Bin Zhang , Huan-Huan Yang , Jia-Xing Lu , Ao Shen , Jun-Ying Song , Juan Yuan , Zhen-Qiang Zhang
{"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 HL<sup>1</sup>-HL<sup>4</sup>. The structures of complexes <strong>1</strong>–<strong>4</strong> were systematically characterized by <sup>1</sup>H 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 HL<sup>1</sup>-HL<sup>4</sup> 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 IC<sub>50</sub> 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}
引用次数: 0
Lysosome-targeted theranostics: Integration of real-time fluorescence imaging and controlled drug delivery via Zn(II)-Schiff Base complexes 溶酶体靶向治疗:实时荧光成像和通过Zn(II)-希夫碱配合物控制给药的集成
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-23 DOI: 10.1016/j.jinorgbio.2025.113015
Xixi Lai , Tianxiao Lu , Fusheng Zhang , Arshad Khan , Yili Zhao , Xin Li , Shuo Xiang , Kuailu Lin
{"title":"Lysosome-targeted theranostics: Integration of real-time fluorescence imaging and controlled drug delivery via Zn(II)-Schiff Base complexes","authors":"Xixi Lai ,&nbsp;Tianxiao Lu ,&nbsp;Fusheng Zhang ,&nbsp;Arshad Khan ,&nbsp;Yili Zhao ,&nbsp;Xin Li ,&nbsp;Shuo Xiang ,&nbsp;Kuailu Lin","doi":"10.1016/j.jinorgbio.2025.113015","DOIUrl":"10.1016/j.jinorgbio.2025.113015","url":null,"abstract":"<div><div>The development of lysosome-targeted theranostic platforms stands at the forefront of precision oncology. However, significant challenges persist in synchronizing real-time diagnostic imaging with spatiotemporal controlled therapeutic delivery. Current systems commonly encounter issues such as suboptimal quantum yields, pH-insensitive release kinetics, and spectral interference between imaging and drug-tracking modes. To address these limitations, we rationally designed a novel series of Zn(II)-Schiff base complexes through coordination chemistry to achieve lysosomal targeting, enhanced optical properties, and microenvironment-responsive drug release. Optical characterization revealed significant red shifts in the absorption and emission spectra after Zn(II) coordination, which can be attributed to the reduction in energy bandgap. Among these complexes, Zn-((2,5-diamino-1,4-benzenedithiol dihydrochloride)-(2,4-Dihydroxybenzaldehyde)) (Zn-MTDH) exhibited the highest quantum yield (63.7 %) and enabled high-contrast lysosomal imaging in 4 T1 breast cancer cells, positioning it as a promising candidate for biological applications. When loaded with camptothecin (CPT), CPT@Zn-MTDH displayed pH-dependent drug release kinetics (81 % cumulative release at pH 5.6 vs. 51 % at pH 7.4 over 36 h). Cellular assays demonstrated that Zn-MTDH exhibits low cytotoxicity and excellent biocompatibility. In contrast, CPT@Zn-MTDH exhibited enhanced cytotoxicity compared to free CPT, highlighting the potential of these complexes for lysosome-targeted cancer therapy. This study establishes Zn(II)-Schiff base complexes as a versatile “track-and-treat” theranostic platform, thereby bridging diagnostic precision with therapeutic efficacy.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113015"},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711080","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}
引用次数: 0
Monomeric class II chelatase with four histidine residues at the active site, designated Mch4 chelatase, shows evolutionary trails from ancestral to descendant-types 活性位点有四个组氨酸残基的单体II类螯合酶,称为Mch4螯合酶,显示了从祖先到后代型的进化轨迹
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-19 DOI: 10.1016/j.jinorgbio.2025.113010
Shoko Ogawa, Yuuma Oyamada, Hiroumi Saito, Takashi Fujishiro
{"title":"Monomeric class II chelatase with four histidine residues at the active site, designated Mch4 chelatase, shows evolutionary trails from ancestral to descendant-types","authors":"Shoko Ogawa,&nbsp;Yuuma Oyamada,&nbsp;Hiroumi Saito,&nbsp;Takashi Fujishiro","doi":"10.1016/j.jinorgbio.2025.113010","DOIUrl":"10.1016/j.jinorgbio.2025.113010","url":null,"abstract":"<div><div>Class II chelatases catalyze the insertion of divalent metal ions into tetrapyrroles during the biosynthesis of metal-tetrapyrroles, and are regarded as standard models for investigating chelation mechanisms. The catalytic core of class II chelatases exhibits either a homodimer- or a monomer-type architecture with similar overall folds and different catalytic His residues: four His residues in the homodimer type and one or two His residues in the monomer type. These structural features of the two types of chelatases have led to the hypothesis that the monomer-type is a “descendant” evolved from the homodimer-type “ancestor”. However, there has been no report on naturally-occurring “evolutionary intermediate”-type of chelatases to support this hypothesis. Here, we show the discovery and characterization of such “evolutionary intermediate”-type chelatases. Because this type of chelatases was classified into <u>m</u>onomeric <u>ch</u>elatases with <u>four</u> histidine residues at the active site, we named these chelatases Mch4. Gene complement analysis showed Mch4s could play a role in Fe<sup>2+</sup> insertion into sirohydrochlorin. Notably, Mch4s did not utilize coproporphyrin III or protoporphyrin IX in vivo assay. In addition, in vitro functional analysis of Mch4s demonstrated that they could utilize Ni<sup>2+</sup>, Co<sup>2+</sup> as well as Fe<sup>2+</sup> insertion into sirohydrochlorin. These findings suggest that nickel chelatase activity with sirohydrochlorin was maintained in the hypothetical class II chelatase evolution from homodimeric ancestor-type, to monomeric evolutionary-intermediate-type Mch4, followed by changes in the metal and tetrapyrrole preferences of some descendant chelatases through further evolution, such as further substitution of His at their active sites.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113010"},"PeriodicalIF":3.8,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686892","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}
引用次数: 0
Impact of ligand esterification on the cytotoxicity against breast cancer cells of ruthenium(II)/dppb pyridinedicarboxylate complexes 配体酯化对钌(II)/dppb吡啶二羧酸配合物对乳腺癌细胞毒性的影响
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-17 DOI: 10.1016/j.jinorgbio.2025.113008
Mariana Santoro de Camargo , Rone Aparecido De Grandis , Ayrton Corrêa Galo , Flávia Aparecida Resende , Pedro Henrique Salgado Marcon , Javier Ellena , João Honorato de Araujo-Neto , Alzir Azevedo Batista
{"title":"Impact of ligand esterification on the cytotoxicity against breast cancer cells of ruthenium(II)/dppb pyridinedicarboxylate complexes","authors":"Mariana Santoro de Camargo ,&nbsp;Rone Aparecido De Grandis ,&nbsp;Ayrton Corrêa Galo ,&nbsp;Flávia Aparecida Resende ,&nbsp;Pedro Henrique Salgado Marcon ,&nbsp;Javier Ellena ,&nbsp;João Honorato de Araujo-Neto ,&nbsp;Alzir Azevedo Batista","doi":"10.1016/j.jinorgbio.2025.113008","DOIUrl":"10.1016/j.jinorgbio.2025.113008","url":null,"abstract":"<div><div>Here we report the synthesis and characterization of five new ruthenium(II) complexes with the general formula [Ru(N<img>O)₂(dppb)], where dppb is 1,4-bis(diphenylphosphino)butane and the N<img>O ligands are derivatives of pyridinecarboxylic acids: picolinic acid (<strong>C20</strong>), 2,3- (<strong>C23</strong>), 2,4- (<strong>C24</strong>), and 2,5-pyridinedicarboxylic acids (<strong>C25</strong>), as well as the monoester derivative of 2,4-pyridinedicarboxylic acid (<strong>C24e</strong>), obtained by Fischer esterification. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR spectroscopy (<sup>1</sup>H and <sup>31</sup>P{<sup>1</sup>H}), and single-crystal X-ray diffraction (for <strong>C23</strong> and <strong>C24</strong>). The stability of the complexes in solution was confirmed by UV–Vis spectroscopy in DMSO and by <sup>31</sup>P{<sup>1</sup>H} NMR in a DMSO/DMEM mixture (for <strong>C24</strong>), with no evidence of significant speciation reactions. Biological assays revealed that complexes <strong>C20</strong> and <strong>C24e</strong> exhibit significant cytotoxic activity and selectivity against human breast cancer cell lines (MCF-7 and MDA-MB-231) over non-tumorigenic HaCaT cells. Notably, <strong>C20</strong> remained active in three-dimensional spheroid models of MCF-7 cells, showing greater potency than cisplatin. Additionally, both <strong>C20</strong> and <strong>C24e</strong> did not induce mutagenic effects or generate intracellular reactive oxygen species, suggesting alternative mechanisms of cytotoxicity. These findings support the potential of picolinic and esterified pyridinedicarboxylic acid ruthenium(II) complexes as promising antitumor agents.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113008"},"PeriodicalIF":3.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704016","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}
引用次数: 0
Photodynamic activity of Zn(II) phthalocyanines containing polyoxyethylene side chains in malignant melanoma and colorectal cancer cell lines 含聚氧乙烯侧链Zn(II)酞菁在恶性黑色素瘤和结直肠癌细胞系中的光动力学活性
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-16 DOI: 10.1016/j.jinorgbio.2025.113007
Gizem Gümüşgöz Çelik , Başak Aru , Mehmet Menaf Ayhan , Gülderen Yanıkkaya Demirel , Ayşe Gül Gürek
{"title":"Photodynamic activity of Zn(II) phthalocyanines containing polyoxyethylene side chains in malignant melanoma and colorectal cancer cell lines","authors":"Gizem Gümüşgöz Çelik ,&nbsp;Başak Aru ,&nbsp;Mehmet Menaf Ayhan ,&nbsp;Gülderen Yanıkkaya Demirel ,&nbsp;Ayşe Gül Gürek","doi":"10.1016/j.jinorgbio.2025.113007","DOIUrl":"10.1016/j.jinorgbio.2025.113007","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is a treatment modality that activates apoptosis as the preferred pathway of cell death by exposing the target area to light of a wavelength within the spectrum of an administered photosensitizer (PS). Here, we aimed to investigate the anticancer mechanisms of non-peripheral zinc phthalocyanines substituted with either four (np-O-ZnPc1 and np-S-ZnPc1) or eight (np-O-ZnPc2 and np-S-ZnPc2) triethylene monomethyl glycol groups to compare the effects of heteroatoms and substituent number in a systematic manner. Comparison with unsubstituted Zn(II)-phthalocyanine (ZnPc) suggests that substitution of triethylene monomethylglycol with ZnPc tends to increase the singlet oxygen yield while decreasing the fluorescence quantum yield for all compounds. In addition, an increasing fluorescence half-life was observed with the exception of np-O-ZnPc2. The cytotoxicity of the compounds was evaluated on colorectal cancer (HCT116), malignant melanoma (SH-4) and a skin keratinocyte cell line (HaCaT). The optimal incubation time and light dose were determined and the half maximal inhibitory concentrations (IC50) for each cell line were calculated. Programmed cell death pathways, mitochondrial function and protein expression of chemokine receptors were examined. The compounds significantly reduced cell viability and promoted apoptosis in both cancer cell lines. Structurally, compounds with oxygen heteroatoms exhibited higher anticancer activity than those with sulfur atoms. The observation of an increase in CCR7 and CXCR4 proteins as a result of PDT highlights the need for further detailed evaluation of the effects of PDT with the offered phthalocyanines on the invasive and migratory properties of cancer cells.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113007"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662531","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}
引用次数: 0
Evaluating indole‑gold(I) based complexes as potential anti lymphoma agents by disrupting the thioredoxin reductase/glutathione peroxidase axis 通过破坏硫氧还蛋白还原酶/谷胱甘肽过氧化物酶轴来评价吲哚-金(I)基配合物作为潜在的抗淋巴瘤药物
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-16 DOI: 10.1016/j.jinorgbio.2025.113004
Sicong Wang , Min Shan , Zhongren Xu , Guizhi Jiang , Mengshi Wang , Yanyu Zhou , Xiao Zhao , Kathryn F. Tonissen , Wukun Liu , Giovanna Di Trapani
{"title":"Evaluating indole‑gold(I) based complexes as potential anti lymphoma agents by disrupting the thioredoxin reductase/glutathione peroxidase axis","authors":"Sicong Wang ,&nbsp;Min Shan ,&nbsp;Zhongren Xu ,&nbsp;Guizhi Jiang ,&nbsp;Mengshi Wang ,&nbsp;Yanyu Zhou ,&nbsp;Xiao Zhao ,&nbsp;Kathryn F. Tonissen ,&nbsp;Wukun Liu ,&nbsp;Giovanna Di Trapani","doi":"10.1016/j.jinorgbio.2025.113004","DOIUrl":"10.1016/j.jinorgbio.2025.113004","url":null,"abstract":"<div><div>Antioxidant systems, especially the thioredoxin (Trx) and glutathione (GSH) systems, represent promising targets for cancer therapy. Overexpression of these systems has been reported in many cancers, including lymphoma and considered as a mechanism of protection for cancer cells from the high levels of reactive oxygen species (ROS). Over several decades, metal-based complexes including gold complexes such as auranofin have shown anticancer activity by targeting thiols and selenol groups in the active site of thioredoxin reductase (TrxR). However, lack of selectivity, severe side effects or resistance to therapy have been widely reported. Recently, glutathione peroxidase (Gpx) has been reported as one of the key proteins that regulate ferroptosis in cells. To expand the armory for targeting antioxidant systems, in this study eleven new indole-metal complexes were synthesized and assessed for their antiproliferative activity in lymphoma cell lines. The indole‑gold(I)-based complexes showed the best anti-lymphoma activity <em>via</em> inhibiting TrxR and Gpx, but not glutathione reductase (GR), when compared to the indole‑iron-based and cobalt-based complexes. Further investigation revealed that two of the indole‑gold(I)-based complexes, <strong>3h</strong> and <strong>3i</strong>, induced the expression of ferroptosis-related genes and an increase in lipid peroxidation, indicating activation of ferroptosis in these cells. The <em>in vivo</em> study also revealed that these complexes significantly inhibited angiogenesis by reducing formation of blood vessels in zebra fish embryos. Overall, these results show the potential of <strong>3h</strong> and <strong>3i</strong> as TrxR and Gpx inhibitors in lymphoma cells, warranting further assessment as anticancer agents and potential inducers of ferroptosis.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113004"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679929","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}
引用次数: 0
Iridium(III) complexes as type I photosensitizers for hypoxic two-photon photodynamic therapy 铱(III)配合物作为I型光敏剂用于缺氧双光子光动力治疗
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-15 DOI: 10.1016/j.jinorgbio.2025.113006
Zanru Tan , Jiang Feng , Zixin Tang , Tao Feng , Taihong Liu , Yukun Zhao , Hui Chao
{"title":"Iridium(III) complexes as type I photosensitizers for hypoxic two-photon photodynamic therapy","authors":"Zanru Tan ,&nbsp;Jiang Feng ,&nbsp;Zixin Tang ,&nbsp;Tao Feng ,&nbsp;Taihong Liu ,&nbsp;Yukun Zhao ,&nbsp;Hui Chao","doi":"10.1016/j.jinorgbio.2025.113006","DOIUrl":"10.1016/j.jinorgbio.2025.113006","url":null,"abstract":"<div><div>Photodynamic therapy (PDT), a non-invasive therapeutic modality, has significantly improved skin cancer treatment in recent years. Nonetheless, the limitations associated with conventional photosensitizers, such as their substantial dependence on oxygen and restricted light penetration, continue to pose considerable challenges for clinical applications. Herein, five Iridium(III) complexes have been developed as type I photosensitizers for two-photon PDT targeting melanoma. These complexes exhibit notable two-photon absorption (TPA) cross-sections (σ2 ≥ 100 GM) and high yields of reactive oxygen species (ROS) under hypoxic conditions, leading to mitochondrial damage and subsequent apoptosis through ROS generation with low doses of single or two-photon excitation. Notably, <strong>Ir4@PEG</strong> exhibits an IC<sub>50</sub> value of 2.1 μM and a phototoxicity index (PI) of 47 under hypoxic conditions. Cellular assays indicate that <strong>Ir4@PEG</strong> initially targets and localizes within lysosomes, where the lysosomal membrane is subsequently compromised upon light stimulation, resulting in <strong>Ir4</strong> transferring and damaging mitochondria, causing cell apoptosis. Additionally, <strong>Ir4@PEG</strong> demonstrates improved tumor penetration, significant ROS production, and marked phototoxicity in hypoxic three-dimensional tumor spheroids. These findings provide new insights into designing oxygen-independent, metal-based two-photon photodynamic therapies against hypoxic melanoma.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113006"},"PeriodicalIF":3.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662529","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}
引用次数: 0
The novel platinum(IV) prodrug of cisplatin axially conjugated with cannabidiol induces mitochondrial dysfunction and synergistically enhances anti-tumor effects 新型铂(IV)前药顺铂轴向偶联大麻二酚诱导线粒体功能障碍,协同增强抗肿瘤作用
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-12 DOI: 10.1016/j.jinorgbio.2025.113003
Rong Lv , Pengmin Shi , Zhiping Lu , Tangli Wei , Jing Yang , Xiali Liao , Bo Yang , Chuanzhu Gao
{"title":"The novel platinum(IV) prodrug of cisplatin axially conjugated with cannabidiol induces mitochondrial dysfunction and synergistically enhances anti-tumor effects","authors":"Rong Lv ,&nbsp;Pengmin Shi ,&nbsp;Zhiping Lu ,&nbsp;Tangli Wei ,&nbsp;Jing Yang ,&nbsp;Xiali Liao ,&nbsp;Bo Yang ,&nbsp;Chuanzhu Gao","doi":"10.1016/j.jinorgbio.2025.113003","DOIUrl":"10.1016/j.jinorgbio.2025.113003","url":null,"abstract":"<div><div>Classical cisplatin-based chemotherapeutic drugs are widely used in clinical practice. In recent years, novel platinum-based antitumor drugs have focused on replacing classical cisplatin-like Pt(II) complexes with relatively inert Pt(IV) prodrugs to overcome drug resistance and reduce toxic side effects. Based on the excellent physiological and pharmacological activities of cannabidiol (CBD), this study designed and synthesized novel Pt(IV) prodrugs W1-W6, which are axial conjugates of cisplatin with CBD and specific active small molecules. These prodrugs demonstrated more significant antitumor activity against tested tumor cell lines. Among them, the multifunctional Pt(IV) prodrug W5, conjugated with CBD and the PDK inhibitor DCA, exhibited excellent activity against both platinum-sensitive and cisplatin-resistant tumor strains. The IC<sub>50</sub> value of W5 for the A549R tumor strain was 8.53 ± 0.76 μM, significantly higher than that of the cisplatin group and 3.64 times the activity of CBD alone, demonstrating strong synergistic antitumor activity and potential to overcome cisplatin resistance. W5 is reduced by GSH in A549R cells, releasing CBD and Pt(II). Pt(II) binds to DNA, inducing damage and inhibiting repair, while CBD activates pro-apoptotic proteins, leading to mitochondrial dysfunction. Simultaneously, W5 reduces the levels of ROS scavengers, triggering endoplasmic reticulum dysfunction. These three mechanisms synergistically promote tumor cell apoptosis and overcome drug resistance. This design integrates multiple mechanisms through axial functionalization, breaking through the limitation of traditional platinum drugs targeting DNA alone, and achieves synergistic effects by regulating metabolism and intervening in the immune microenvironment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113003"},"PeriodicalIF":3.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632490","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}
引用次数: 0
Tumor microenvironment responsive smart nanoplatform for synergistic tumor therapy through co-enhancement of GSH depletion and hypoxia relief 肿瘤微环境响应智能纳米平台,通过协同增强谷胱甘肽耗竭和缺氧缓解协同肿瘤治疗
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-11 DOI: 10.1016/j.jinorgbio.2025.113005
Pengfei Yang , Jie Zhang , Yi Chang , Lingxue Tang , Guanglei Ma , Xinhe Liu , Fangli Gao , Xiaoming Ma , Yuming Guo
{"title":"Tumor microenvironment responsive smart nanoplatform for synergistic tumor therapy through co-enhancement of GSH depletion and hypoxia relief","authors":"Pengfei Yang ,&nbsp;Jie Zhang ,&nbsp;Yi Chang ,&nbsp;Lingxue Tang ,&nbsp;Guanglei Ma ,&nbsp;Xinhe Liu ,&nbsp;Fangli Gao ,&nbsp;Xiaoming Ma ,&nbsp;Yuming Guo","doi":"10.1016/j.jinorgbio.2025.113005","DOIUrl":"10.1016/j.jinorgbio.2025.113005","url":null,"abstract":"<div><div>As innovative therapeutic strategy, chemodynamic therapy (CDT) and photodynamic therapy (PDT) show great promise for tumor therapy. However, their therapeutic efficacy is seriously limited by the hypoxia and insufficient H<sub>2</sub>O<sub>2</sub> supply of the tumor microenvironment. Juglone (JUG), a naturally-occurring naphthoquinone, can increase the intracellular H<sub>2</sub>O<sub>2</sub> concentration and serve as an inhibitor of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1. Herein, a nanoplatform composed of Fe-based metal-organic framework core, MnO<sub>2</sub> layer, JUG payload, and hyaluronic acid (HA) decoration (Fe-TCPP@MnO<sub>2</sub>@JUG@HA) was designed and prepared. The MnO<sub>2</sub> layer can prevent the phototoxicity of tetrakis (4-carboxyphenyl)porphyrin (TCPP) during transportation and catalyze H<sub>2</sub>O<sub>2</sub> to produce O<sub>2</sub> to enhance the PDT efficacy. HA can improve the delivery efficiency to tumor. Then Fe<sup>3+</sup> was reduced to Fe<sup>2+</sup> and MnO<sub>2</sub> was reduced to Mn<sup>2+</sup> because of the weak acidity and high concentration glutathione (GSH), causing the nanoplatform collapse, TCPP activation, and JUG release. GSH-depletion reduce the reactive oxygen species (ROS) scavenging effect and further enhance the PDT efficacy, inhibited the biosynthesis of lipid repair enzyme glutathione peroxidase 4 and promoted the ferroptosis efficiency by destroying redox balance. This PDT/CDT/chemotherapy triple synergistic apoptosis-ferroptosis strategy exhibited good tumor therapeutic efficacy and excellent biocompatibility, implying the promising future for efficient tumor treatment.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 113005"},"PeriodicalIF":3.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632489","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}
引用次数: 0
Microbiological applications of the saccharinatecopper(II) complex (Cu-Sac) 糖化铜(II)配合物(Cu-Sac)的微生物学应用
IF 3.8 2区 化学
Journal of Inorganic Biochemistry Pub Date : 2025-07-08 DOI: 10.1016/j.jinorgbio.2025.112990
Patricia Appelt , Aline B. Schons , Lucéli Roloff , Mário A.A. Cunha , Juan C. Villalba , Davi Back , Henrique E. Toma , Fauze J. Anaissi
{"title":"Microbiological applications of the saccharinatecopper(II) complex (Cu-Sac)","authors":"Patricia Appelt ,&nbsp;Aline B. Schons ,&nbsp;Lucéli Roloff ,&nbsp;Mário A.A. Cunha ,&nbsp;Juan C. Villalba ,&nbsp;Davi Back ,&nbsp;Henrique E. Toma ,&nbsp;Fauze J. Anaissi","doi":"10.1016/j.jinorgbio.2025.112990","DOIUrl":"10.1016/j.jinorgbio.2025.112990","url":null,"abstract":"<div><div>The tetraaqua-<em>bis</em>(saccharinato)copper(II) dihydrate complex (Cu-Sac) was synthesized, structurally characterized by single-crystal X-ray diffraction, and tested for antioxidant and antimicrobial activity. In this complex, deprotonated saccharin ligands coordinate monodentate via nitrogen in a trans configuration to copper, with four water molecules also bound. Its distorted octahedral geometry fits the formula [M(Sac)<sub>2</sub>(H<sub>2</sub>O)<sub>4</sub>]·2H<sub>2</sub>O. The Cu-Sac complex showed good antioxidant efficacy in DPPH and hydrogen peroxide scavenging assays and was effective against ten microorganisms in both pellet and solution forms. Notably, this study also assessed the use of the pigment in commercial white paint at 10 % and 20 % concentrations. MIC data indicated that the complex exhibits broad-spectrum antimicrobial activity, showing efficacy against Gram-negative and Gram-positive bacterial strains, and fungicidal activity against yeast strains. The copper saccharinate paint showed promising results in the disk diffusion test, producing inhibition zones of 27.50 ± 4.0 mm for <em>P. mirabilis</em>, exceeding the inhibition zones observed with standard antibiotics. An increase in the concentration of the complex in the paint was also shown to result in greater antibacterial efficacy. The activity index obtained for the paint samples showed good results, with the Cu-Sac 20 % sample being particularly noteworthy, especially against the <em>S. epidermidis</em> and <em>E. faecium</em> strains, with indices ≥1. These findings suggest that the Cu-Sac complex has potential as an antimicrobial pigment or surface-applied antibiotic agent, indicating promising prospects for industrial applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"272 ","pages":"Article 112990"},"PeriodicalIF":3.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597084","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}
引用次数: 0
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