Synthesis and anticancer studies of Ru/Ir arene complexes bearing oleanolic acid in acute promyelocytic leukemia cells

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2025-05-21 DOI:10.1016/j.jinorgbio.2025.112959

Xiang-Yu Dai , Zheng-Qi Shen , Yating Zhang, Hanxue Liu, Meng Ren, Peisen Wang, Ji Li, Xuling Xue, Hong-Ke Liu

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引用次数: 0

Abstract

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, ole-Ru and ole-Ir, by fusing the natural product oleanolic acid as the ligand into two metal (ruthenium and iridium) precursors. Ole-Ru and ole-Ir 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.

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含齐墩果酸的Ru/Ir芳烃配合物在急性早幼粒细胞白血病细胞中的合成及抗癌研究

急性白血病是一种起源于骨髓和造血组织的癌症，对人类健康构成重大威胁。化疗可能会引起一系列的副作用，并进一步给病人带来更大的痛苦。因此，降低治疗白血病药物的毒性已成为一项重大挑战。在本研究中，我们将天然产物齐墩果酸作为配体融合到两种金属（钌和铱）前体中，开发了两种非铂抗癌剂ole-Ru和ole-Ir。Ole-Ru和ole-Ir不仅通过凋亡途径对NB4细胞表现出显著的选择性和细胞毒性，而且对正常肺成纤维细胞也表现出低毒性，提示其靶向治疗急性白血病细胞的潜力。这项工作提出了一种合理的设计策略，旨在抑制NB4细胞的金属基抗癌复合物，并扩大了金属药物在白血病治疗中的应用范围。

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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.