{"title":"Preparation of ferrocene‑iridium(III) acylhydrazone complexes and their anticancer application against A549 cell line","authors":"Wenzhi Yang , Jia Wen , Xicheng Liu , Jinfeng Liu","doi":"10.1016/j.jinorgbio.2025.112899","DOIUrl":null,"url":null,"abstract":"<div><div>Two ferrocene‑iridium(III) acylhydrazone complexes (<strong>Fe-Ir1</strong> and <strong>Fe-Ir2</strong>) were designed and synthesized, which showed excellent anti-proliferative activity against A549 human lung adenocarcinoma and A549/DDP (cisplatin-resistant) cell lines, especially for <strong>Fe-Ir1</strong> (IC<sub>50</sub> = 10.2 ± 0.4 μM, twice that of cisplatin). Meanwhile, <strong>Fe-Ir1</strong> showed low toxicity to BEAS-2B cells (normal dividing human bronchial epithelial cells), indicating its favorable selectivity. <strong>Fe-Ir1</strong> entered A549 cells following an non-energy-dependent pathway, targeted lysosomes, induced changes in lysosomal membrane permeability, reduced glycolytic stress, arrested cell cycle, then promoted early-stage apoptosis and effectively inhibited cell migration. Western blotting also showed that the <strong>Fe-Ir1</strong> could promote the expression of Bax protein and inhibited Bcl-2 and PARP protein in A549 cells. In vivo experiments demonstrated that <strong>Fe-Ir1</strong> had significant capabilities in inhibiting tumor growth, cancer cell metastasis and spread. In conclusion, <strong>Fe-Ir1</strong> holds promise as a potential alternative to platinum-based drugs and warrants further research, offering more hope and vitality to cancer patients.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"269 ","pages":"Article 112899"},"PeriodicalIF":3.8000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inorganic Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0162013425000790","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Two ferrocene‑iridium(III) acylhydrazone complexes (Fe-Ir1 and Fe-Ir2) were designed and synthesized, which showed excellent anti-proliferative activity against A549 human lung adenocarcinoma and A549/DDP (cisplatin-resistant) cell lines, especially for Fe-Ir1 (IC50 = 10.2 ± 0.4 μM, twice that of cisplatin). Meanwhile, Fe-Ir1 showed low toxicity to BEAS-2B cells (normal dividing human bronchial epithelial cells), indicating its favorable selectivity. Fe-Ir1 entered A549 cells following an non-energy-dependent pathway, targeted lysosomes, induced changes in lysosomal membrane permeability, reduced glycolytic stress, arrested cell cycle, then promoted early-stage apoptosis and effectively inhibited cell migration. Western blotting also showed that the Fe-Ir1 could promote the expression of Bax protein and inhibited Bcl-2 and PARP protein in A549 cells. In vivo experiments demonstrated that Fe-Ir1 had significant capabilities in inhibiting tumor growth, cancer cell metastasis and spread. In conclusion, Fe-Ir1 holds promise as a potential alternative to platinum-based drugs and warrants further research, offering more hope and vitality to cancer patients.
期刊介绍:
The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.