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含β-取代羧酸根乙二胺/丙二胺配体的铂(II/IV)配合物:制备、表征及活性

Platinum(II/IV) complexes with -substituted carboxylate ethylenediamine/propylenediamine ligands: preparation, characterization and activity.

作者信息

Richter Stefan, Lönnecke Peter, Bovan Dijana, Andrian Nicoleta, Stoean Bianca, Lehene Maria, Silaghi-Dumitrescu Radu, Gaina Luiza, Mijatović Sanja, Maksimović-Ivanić Danijela, Kaluđerović Goran N, Hey-Hawkins Evamarie

机构信息

Institute of Inorganic Chemistry, Faculty of Chemistry and Mineralogy, Leipzig University, Johannisallee 29, 04103 Leipzig, Germany.

Department of Immunology, Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.

出版信息

Dalton Trans. 2025 Feb 25;54(9):3597-3609. doi: 10.1039/d4dt03041a.

Abstract

The synthesis and characterization of novel platinum(II) and platinum(IV) complexes derived from unsymmetrical ethylene or propylenediamine derivatives are presented. IR spectroscopy and ESI mass spectrometry techniques were employed to characterize the complexes, revealing distinctive absorption bands and isotope patterns. Furthermore, the complexes were characterized by H and C NMR spectroscopy. Single-crystal X-ray structural analysis elucidated the coordination geometry and intermolecular interactions of complexes 3, 4 and 6. Cytotoxicity evaluation of the complexes on various cell lines highlighted complex 3 as the most active, realizing its tumoricidal activity through induction of apoptosis and increased total caspase activity in MCF-7 cells. Since its application is followed by cytoprotective autophagy, the effectiveness can be additionally empowered by concomitant inhibition of this process. Furthermore, the Pt compound 3 induces oxidative stress in hemoglobin, and is reducible by glutathione, suggesting its potential as a carrier for the active Pt precursor 2a to cancer cells without increasing cytotoxicity. Cyclic voltammetry corroborates the ability of complex 3 to undergo reduction under physiological conditions.

摘要

本文介绍了由不对称乙烯或丙二胺衍生物衍生而来的新型铂(II)和铂(IV)配合物的合成与表征。采用红外光谱和电喷雾电离质谱技术对配合物进行表征,揭示了独特的吸收带和同位素模式。此外,通过氢核磁共振光谱和碳核磁共振光谱对配合物进行了表征。单晶X射线结构分析阐明了配合物3、4和6的配位几何结构和分子间相互作用。对配合物在各种细胞系上的细胞毒性评估表明,配合物3活性最高,通过诱导MCF-7细胞凋亡和增加总半胱天冬酶活性实现其杀肿瘤活性。由于其应用伴随着细胞保护性自噬,通过同时抑制这一过程可进一步增强其有效性。此外,铂化合物3可诱导血红蛋白中的氧化应激,并可被谷胱甘肽还原,这表明它有潜力作为活性铂前体2a的载体转运至癌细胞,而不增加细胞毒性。循环伏安法证实了配合物3在生理条件下发生还原的能力。

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