Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Abstract

Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory concentration) levels of Cu(ClO 4 ) 2 · 6H 2 O and [Cu(phendio) 3 ](ClO 4 ) 2 · 4H 2 O (phendio = 1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and amphotericin B required to achieve the MIC 90 whereas pre-growth in AgClO 4 and [Ag(phendio) 2 ]ClO 4 resulted in a small decrease in the relevant MIC 90 values. The copper complexes reduce the oxygen consumption of C. albicans while the silver complexes increase oxygen consumption. In addition, pregrowth of cells in the copper complexes resulted in a lower ergosterol content while the silver complexes induced an elevation in ergosterol synthesis.The ability of copper and silver complexes to alter the susceptibility of C. albicans to miconazole and amphotericin B may be influenced by their action on respiration, since reduced respiration rates correlate with reduced cellular ergosterol which is the target for amphotericin B. Lower levels of ergosterol have previously been associated with elevated tolerance to this drug. In the case of reduced sensitivity to miconazole, tolerance may be mediated by lower ergosterol synthesis giving rise to fewer toxic side products once biosynthesis is inhibited by miconazole.Abbreviations: phendio = 1,10-phenanthroline-5,6-dione. phen = 1,10-phenanthroline

Caspofungin Kills Candida albicans by Causing both Cellular Apoptosis and Necrosis

“…Taken together, therefore, the data suggest that caspofungin at concentrations below the MIC causes C. albicans cells to undergo apoptosis but that increasing caspofungin concentrations above the MIC does not further induce programmed cell death responses. Previous studies have shown that several stimuli, including acetic acid (7), hydrogen peroxide (27), 1,10-phenanthroline metal complexes (28), silver-coumarin complexes (17), diallyl disulfide (29), farsenol (26), lactoferrin (30), defensins (31), and the antifungal agent amphotericin B (9), cause C. albicans cells to undergo apoptosis. Our data demonstrate that cell wall stress stemming from inhibition of (1,3)-␤-D-glucan, as caused by caspofungin and Zymolyase (at concentrations Ն0.1 mg/ml), is also a trigger for apoptosis.…”

Mechanism of action of coumarin and silver(I)–coumarin complexes against the pathogenic yeast Candida albicans

“…Previous studies have shown that fungal respiration is aVected when cells are exposed to metal-based drugs (Coyle et al, 2003;Eshwika et al, 2004;McCann et al, 2004). Therefore, the respiration rate of cells exposed to each of the diVerent coumarin-silver complexes was determined.…”

Imidazole Schiff base ligands: Synthesis, coordination complexes and biological activities

“…However, some of the latter complexes displayed significantly greater anti-Candida activity compare d to the present complexes. In addition, the present Ag(I) complexes had activities similar to that of the prescription drug, miconazole (MIC 90 against C. albicans = 19 lM [17]). …”