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 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.
McCann
Malachy
M
Chemistry Department, National University of Ireland Maynooth, Maynooth, Co Kildare, Ireland. mmcann@may.ie
Coyle
Barry
B
McKay
Sinead
S
McCormack
Paul
P
Kavanagh
Kevin
K
Devereux
Michael
M
McKee
Vickie
V
Kinsella
Paula
P
O'Connor
Robert
R
Clynes
Martin
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002176:Candida albicans / Q000378:metabolism; D045744:Cell Line, Tumor; D003300:Copper / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D048749:Cytokinesis; D004271:DNA, Fungal / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000737:chemistry; D008854:Microscopy, Electron; D008956:Models, Chemical; D010472:Perchlorates / Q000138:chemical synthesis / Q000494:pharmacology*; D010618:Phenanthrolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011487:Protein Conformation; D014965:X-Rays
D000970:Antineoplastic Agents; D004271:DNA, Fungal; D005656:Fungal Proteins; D008670:Metals; D010472:Perchlorates; D010618:Phenanthrolines; C062280:copper(II) perchlorate; C037153:1,10-phenanthroline-5,6-dione; D003300:Copper