New platinum(II) and palladium(II) complexes with substituted terpyridine ligands: synthesis and characterization, cytotoxicity and reactivity towards biomolecules

Autor: Tiziano Marzo, Federica Scaletti, Lara Massai, Luigi Messori, Aleksandar Savić, Richard Hoogenboom, Gianluca Bartoli, Kristof Van Hecke, Rik Van Deun
Rok vydání: 2018
Předmět:
Stereochemistry
RNase P
Pyridines
Anticancer drugs
Interactions with biomolecules
Platinum and palladium complexes
Single crystal X-ray diffraction analysis
Biochemistry
chemistry.chemical_element
Antineoplastic Agents
General Biochemistry
Genetics and Molecular Biology
Biomaterials
Metal
03 medical and health sciences
chemistry.chemical_compound
Structure-Activity Relationship
Coordination Complexes
Cell Line
Tumor
Humans
Reactivity (chemistry)
Cytotoxicity
030304 developmental biology
Cell Proliferation
Platinum
0303 health sciences
biology
Dose-Response Relationship
Drug
Molecular Structure
Cytochrome c
030302 biochemistry & molecular biology
Metals and Alloys
chemistry
visual_art
biology.protein
visual_art.visual_art_medium
Terpyridine
Cisplatin
Drug Screening Assays
Antitumor
General Agricultural and Biological Sciences
Palladium
Zdroj: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 32(1)
ISSN: 1572-8773
Popis: A series of palladium(II) (1-3) and platinum(II) chloride complexes (4 and 5) with 2,2':6',2″-terpyridine (terpy) derivatives substituted at the 4' position, was synthesized and fully characterized. Single crystal X-ray diffraction analysis of complexes 2, 3 and 5 showed tridentate coordination of the 4'-substituted terpyridine (terpy) ligands to the metal center. Moreover, in vitro cytotoxic activity of these complexes toward a panel of human cancer cell lines (lung cancer A549, colorectal cancer HCT116, ovarian cancer IGROV-1) and toward normal cell line HDF (dermal fibroblast) was determined by Trypan Blue exclusion assay. Overall, the tested compounds manifested a relevant cytotoxicity for the selected cancer cell lines with complex 4 also showing a modest cytotoxicity on the normal cell lines. To better understand the mode of action of these metal complexes, their reactivity with three model proteins, i.e. hen egg white lysozyme (HEWL), cytochrome c (cyt c) and ribonuclease A (RNase A) were comparatively investigated through ESI-MS analysis. The results highlighted a different behavior between the two series of complexes being platinum compounds more reactive toward RNase and cyt c than palladium compounds. Based on the obtained results, it is proposed that in presence of RNase A and cyt c, the platinum complexes undergo activation through release of labile ligands followed by binding to the protein. In contrast, palladium complexes revealed a far lower reactivity implying the likely occurrence of a different mechanism of action.
Databáze: OpenAIRE
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