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新型双齿胺配体以及钯(II)和铂(II)配位与生物活性之间的相互作用

Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity.

作者信息

Oliveira Laiane S, Rosa Letícia B, Affonso Daniele D, Santos Igor A, Da Silva Jennyfer C, Rodrigues Gustavo C, Harris Mark, Jardim Ana Carolina G, Nakahata Douglas H, Sabino José R, de Carvalho João E, Miguel Danilo C, Ruiz Ana Lucia T G, Abbehausen Camilla

机构信息

Institute of Chemistry, University of Campinas, Cidade Universitária Zeferino Vaz - Barão Geraldo, Campinas, São Paulo, Brazil.

Institute of Biology, University of Campinas, Cidade Universitária Zeferino Vaz -, Barão Geraldo, Campinas, São Paulo, Brazil.

出版信息

Chembiochem. 2024 Mar 15;25(6):e202300696. doi: 10.1002/cbic.202300696. Epub 2024 Feb 12.

Abstract

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. H NMR, Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI of 10.5 μM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 μM.

摘要

自顺铂取得成功后,作为抗癌剂的铂(II)和钯(II)配位氮供体配体已得到广泛研究。在这项工作中,设计了一种新型双齿氮供体配体N-[[4-(苯甲氧基)苯基]甲基]-2-吡啶甲胺,以探索其铂(II)和钯(II)配合物的抗寄生虫、抗病毒和抗肿瘤活性。化学和光谱表征证实了[MLCl]配合物的形成,其中M = 铂(II)和钯(II)。单晶X射线衍射证实了钯(II)配合物为平面正方形几何结构。铂(II)配合物的光谱表征表明其结构相似。配合物二甲基亚砜溶液的1H NMR、195Pt NMR和高分辨电喷雾电离质谱(+)分析表明,两种化合物将与吡啶反位的氯与溶剂分子进行交换,但反应速率不同。对配体和两种配合物进行了体外抗肿瘤、抗利什曼原虫和抗病毒活性测试。铂(II)配合物对NCI/ADR-RES(多药耐药卵巢癌细胞系)的半数生长抑制浓度(GI)为10.5 μM。配体和钯(II)配合物显示出良好的抗严重急性呼吸综合征冠状病毒2(SARS-CoV-2)活性,在浓度为50 μM时病毒复制减少约65%。

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