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Abstract

The mode of action of the anti-fungal compounds, 1,10-phenanthroline (phen), [Cu(phen)2(mal)] x 2H2O, [Mn(phen)2(mal)] x 2H2O and [Ag2(phen)3(mal)] x 2H2O (malH2 = malonic acid), was examined using the pathogenic yeast Candida albicans. The compounds have minimum inhibitory concentrations (MIC's) in the range 1.25-5.0 microg cm(-3) and at a concentration of 10 microg cm(-3) display some fungicidal activity. Yeast cells exposed to these drugs show a diminished ability to reduce 2,3,5-triphenyltetrazolium chloride (TTC), indicating a reduction in respiratory function. Treating exponential and stationary phase yeast cells with phen and the Cu(II) and Mn(II) complexes causes a dramatic increase in oxygen consumption. All of the drugs promote reductions in the levels of cytochromes b and c in the cells, whilst the Ag(I) complex also lowers the amount of cytochrome aa3. Cells treated with phen and the Cu(II) and Ag(I) species show reduced levels of ergosterol whilst the Mn(II) complex induces an increase in the sterol concentration. The general conclusion is that the drugs damage mitochondrial function and uncouple respiration. That the drugs are not uniformly active suggests their bioactivity has a degree of metal-ion dependency. Phen and metal-phen complexes represent a novel set of highly active anti-fungal agents whose mode of action is significantly different to that of the polyene and azole prescription drugs.

Synthesis, antimicrobial activity and chemotherapeutic potential of inorganic derivatives of 2-(4′-thiazolyl)benzimidazole{thiabendazole}: X-ray crystal structures of [Cu(TBZH)2Cl]Cl·H2O·EtOH and TBZH2NO3 (TBZH=thiabendazole)

“…Complex 5 exhibits the greatest fungitoxic activity and indeed is comparable to the prescription drug ketoconazole at this concentration. Preliminary studies on the mode of action of the copper TBZH complexes have revealed that they cause a reduction in the ergosterol content of the fungal cells [30] which was also found to be the case for the phenanthroline complexes previously reported [20].…”

“…The mode of action of 1,10-phenanthroline and a number of our potent anti-candida metal complexes {M ¼ Cu(II), Mn(II) or Ag(I)} [20] was examined. The phen and its metal complexes had minimum inhibitory concentrations (MICs) in the range 1.25-5 lg/ml and at concentration of 10 lg/ml they displayed some fungicidal activity.…”

Synthesis, Characterization and Antibacterial Activity of Cobalt(iii) Complex With Phenanthroline and Maltose

“…Examples are the complexes [Cu(phen) 2 mal)]•2H 2 O and [Ag 2 (phen) 2 (mal)]•2H 2 O (phen = 1,10-phenanthroline, malH 2 = malonic acid) reported by B. Coyle et al which inhibit the growth of Candida albicans [8].…”

Synthesis, characterization and antibacterial activity of 2-p-tolyl-1H-imidazo[4,5-f][1,10] phenanthroline and its Co(II), Ni(II) and Cu(II) complexes

“…The photochemical and redox properties of complexes can be varied systematically through appropriate substitution on the phenanthroline rings [15][16][17]. 1,10-Phenanthroline, as well as some of its derived complexes, do exhibit antimicrobial properties [18,19].…”