title: 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: 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 micromol/L. The complex RuCl3(CTZ)3 x 2CH3OH (1f) (MIC = 0.75 micromol/L) was, although modestly, the only one able to increase the fungistatic activity of the parental drug (MIC = 1 micromol/L). On the other hand, at a sub-MIC concentration (0.5 micromol/L), the complexes [Cu(KTZ)Cl2]2 x 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.
authors.affiliation: Chemistry Center, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. mnavarro@ivic.ve
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
authors.forename: Ibis
authors.initials: I
authors.lastname: Colmenares
authors.forename: Heriberto
authors.initials: H
authors.lastname: Correia
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hernández
authors.forename: Yelitza
authors.initials: Y
authors.lastname: Ching
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Millán
authors.forename: Luis E
authors.initials: LE
authors.lastname: Ojeda
authors.forename: Mait
authors.initials: M
authors.lastname: Velásquez
authors.forename: Germán
authors.initials: G
authors.lastname: Fraile
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003022:Clotrimazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008163:Luminescent Measurements; D008670:Metals / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D008670:Metals; D006046:Gold; D003300:Copper; D012428:Ruthenium; D003022:Clotrimazole; D007654:Ketoconazole