Synthesis and X-ray crystal structure of [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells

The Cu(II) and Ag(I) complexes, [Cu(phendio)3](ClO4)2 x 4H2O and [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrah...

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Bibliographic Details
Published in:Biometals 2004-12, Vol.17 (6), p.635-645
Main Authors: McCann, Malachy, Coyle, Barry, McKay, Sinead, McCormack, Paul, Kavanagh, Kevin, Devereux, Michael, McKee, Vickie, Kinsella, Paula, O'Connor, Robert, Clynes, Martin
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Candida albicans - metabolism
Cell division
Cell Line, Tumor
Cell morphology
Copper
Copper - pharmacology
Crystal structure
Crystallography, X-Ray
Cytokinesis
DNA, Fungal - metabolism
Fungal Proteins - metabolism
Humans
Mammals
Metals
Metals - chemistry
Microscopy, Electron
Models, Chemical
Perchlorate
Perchlorates - chemical synthesis
Perchlorates - pharmacology
Phenanthrolines - chemical synthesis
Phenanthrolines - pharmacology
Protein Conformation
Salts
X-Rays
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Summary:The Cu(II) and Ag(I) complexes, [Cu(phendio)3](ClO4)2 x 4H2O and [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. 'Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH3CO2, AgNO3 and AgClO4 x H2O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to 'metal-free' phendio, simple Ag(I) salts and [Ag(phendio)2]ClO4 causes extensive, non-specific DNA cleavage. 'Metal-free' phendio and [Ag(phendio)2]ClO4 induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells.
ISSN:0966-0844
1572-8773
DOI:10.1007/s10534-004-1229-5