Preparation of ferrocene‑iridium(III) acylhydrazone complexes and their anticancer application against A549 cell line

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2025-03-15 DOI:10.1016/j.jinorgbio.2025.112899

Wenzhi Yang , Jia Wen , Xicheng Liu , Jinfeng Liu

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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.

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

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.