In vitro Activities of Transition Metal Derivatives of Ketoconazole and Clotrimazole against a Wild Type Strain of Saccharomyces cerevisiae in Absence or Presence of Human Neutrophils

Abstract

Summary In vitro activities of a series of gold, copper and ruthenium clotrimazole (CTZ, CAS 23593-75-1) and ketoconazole (KTZ, CAS 65277-42-1) derivatives were investigated individually and in combination with human neutrophils (PMNs) against a wild type strain of Saccharomyces cerevisiae. For 11 out of 12 tested metal complexes, the minimal inhibitory concentrations (MICs) at which 100 % of yeast growth was inhibited ranged from 0.75 to 3.0 ?mol/L. The complex RuCl3(CTZ)3 ? 2CH3OH (1f) (MIC = 0.75 ?mol/L) was, although modestly, the only one able to increase the fungistatic activity of the parental drug (MIC = 1 ?mol/L). On the other hand, at a sub-MIC concentration (0.5 ?mol/L), the complexes [Cu(KTZ)Cl2]2 ? 2H2O (2c) and RuCl2(KTZ)2 (2e) displayed synergistic fungicidal effects with PMNs whereas phagocytic capacity was enhanced by complexes [Cu(KTZ)3Cl2] (2b) and RuCl2(KTZ)2 (2e). The findings suggest that the metal-based agents may give rise to drugs with improved antifungal properties.

Effects of a derivative thiazoline/thiazolidine azine ligand and its cadmium complexes on phagocytic activity by human neutrophils

“…Some coordination compounds, like zinc(II) complex with the organic ligand 2-(3,4-dichlorophenyl)imino-N-(4H-5,6-dihydro-1,3-thiazin-2-yl)tetrahydro-1,3-thiazine [4] and copper(II) and ruthenium(II) complexes of the antifungal drug Ketoconazole [3] improve phagocytosis with respect to organic ligand. In other cases, metal complexes do not affect neutrophils phagocytosis as occur for one zinc(II) complex [4] and some gold(I), copper(II) and ruthenium(II) complexes [3]. Finally, in the case of certain diclofenac transition metal complexes [5] the phagocytosis decreases with respect to the drug.…”

“…Likewise, coordination compounds interfere with in vitro phagocytosis showing either improve, like copper(II) and ruthenium(II) complexes of the antifungal drug Ketoconazole [3] and one zinc(II) complex with the organic ligand 2- (3,4-dichlorophenyl)imino-N-(4H-5,6-dihydro-1,3-thiazin-2-yl)tetrahydro-1,3-thiazine [4], or decrease, as it is the case of certain diclofenac transition metal complexes [5].…”