Selective cytotoxicity and antifungal properties of copper(II) and cobalt(II) complexes with imidazole-4-acetate anion or 1-allylimidazole

SCIENTIFIC REPORTS(2019)

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摘要
The physicochemical properties of metal complexes determine their potential applications as antitumor agents. In this study, the antitumor properties of mononuclear cobalt(II) and copper(II) coordination compounds (stoichiometry: [Co(iaa) 2 (H 2 O) 2 ]·H 2 O (iaa = imidazole-4-acetate anion), [Co(1-allim) 6 ](NO 3 ) 2 (1-allim = 1-allylimidazole), [Cu(iaa) 2 H 2 O] and [Cu(1-allim) 4 (NO 3 ) 2 ]) and their ligands have been evaluated on human lung carcinoma A549 cells and normal bronchial BEAS-2B cells. Designing the chemical structure of new antitumor agents the possible interactions with macromolecules such as DNA or proteins should be take into account. PCR gene tlr4 product served as DNA model, whereas lysozyme and phage-derived endolysin (both peptidoglycan degrading enzymes) were applied as protein/enzyme model. The interactions were analysed using PCR-HRM and circular dichroism, FT-IR, spectrophotometry, respectively. Additionally, the antimicrobial properties of the complexes at a non-cytotoxic concentration were analyzed against S. aureus, E. coli, P. aeruginosa and C. albicans strains. The results obtained in this study showed the selective cytotoxicity of metal complexes, mainly [Cu(1-allim) 4 (NO 3 ) 2 ] towards tumor cells. From all tested compounds, only [Co(iaa) 2 (H 2 O) 2 ] . H 2 O non-covalently interacts with DNA. Cu(II) and Co(II) complexes did not affect the secondary conformation of tested proteins but modified the hydrolytic activity of enzymes (lysozyme and endolysin). Moreover, only [Co(iaa) 2 (H 2 O) 2 ] . H 2 O exhibited the antifungal properties. In conclusion, Co(II) and Cu(II) metal complexes bearing two imidazole-4-acetate ligands seemed to be promising antitumor and antifungal agents for future drug design and application.
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关键词
antifungal properties,selective cytotoxicity,copperii,cobaltii
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