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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

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

Maribel Navarro, Ibis Colmenares, Heriberto Correia, Alexandra Hernández, Yelitza Ching, Yolanda Millán, Luis E Ojeda, Mait Velásquez, Germán Fraile

Arzneimittelforschung. 2004;54(11):746-51.

PMID: 15612615

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP65277421-B	Ketoconazole - CAS 65277-42-1		65277-42-1	Price

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