Antimicrobial Activity of Silver Camphorimine Complexes against Candida Strains.

Joana P Costa,M Fernanda N N Carvalho,M Joana F Pinheiro,Fernanda Marques,Sílvia A Sousa,Nuno P Mira,M Conceição Oliveira,Jorge H Leitão,Ana M Botelho Do Rego

doi:10.3390/antibiotics8030144

Joana P Costa, M Fernanda N N Carvalho + Show 7 more

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https://doi.org/10.3390/antibiotics8030144

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Journal: Antibiotics	Publication Date: Sep 10, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: University of Lisbon

Abstract

Hydroxide [Ag(OH)L] (L = IVL, VL, VIL, VIIL), oxide [{AgL}2}(μ-O)] (L = IL, IIL, IIIL, VL, VIL) or chloride [AgIIL]Cl, [Ag(VIL)2]Cl complexes were obtained from reactions of mono- or bicamphorimine derivatives with Ag(OAc) or AgCl. The new complexes were characterized by spectroscopic (NMR, FTIR) and elemental analysis. X-ray photoelectron spectroscopy (XPS), ESI mass spectra and conductivity measurements were undertaken to corroborate formulations. The antimicrobial activity of complexes and some ligands were evaluated towards Candida albicans and Candida glabrata, and strains of the bacterial species Escherichia coli, Burkholderia contaminans, Pseudomonas aeruginosa and Staphylococcus aureus based on the Minimum Inhibitory Concentrations (MIC). Complexes displayed very high activity against the Candida species studied with the lowest MIC values (3.9 µg/mL) being observed for complexes 9 and 10A against C. albicans. A significant feature of these redesigned complexes is their ability to sensitize C. albicans, a trait that was not found for the previously investigated [Ag(NO3)L] complexes. The MIC values of the complexes towards bacteria were in the range of those of [Ag(NO3)L] and well above those of the precursors Ag(OAc) or AgCl. The activity of the complexes towards normal fibroblasts V79 was evaluated by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Results showed that the complexes have a significant cytotoxicity.

Highlights

The resistance of microorganisms to conventional antimicrobials is presently a serious threat to public health worldwide, representing a huge financial burden for public health systems
The objective was to keep the structure of the complexes while replacing the nitrate ion by a less acidic anionic co-ligand (OAc− or Cl− ), aiming to overcome the lack of antifungal activity displayed by the nitrate complexes [Ag(NO3 )L] towards C. albicans
The acidic character of the nitrate ion was hypothesized to favor the reduction processes mediated by a protein existing in C. albicans, but not at other Candida species

Summary

Introduction

The resistance of microorganisms to conventional antimicrobials is presently a serious threat to public health worldwide, representing a huge financial burden for public health systems. Fungal infections, and notably candidiasis caused by members of the Candida genus, are of increasing concern worldwide. These infections range from superficial infections to life-threatening disseminated mycoses [2,3]. The increasing resistance of pathogenic microorganisms to existing antimicrobials has been accompanied by a scarce increment in the number of alternative compounds commercially available, due to the low interest shown by the pharma industry in the search and development of new antimicrobials [6,7]. It is urgent to find novel molecules with chemical characteristics different from those commercially available These molecules should display new modes of action and point to new microbial targets [8]. Many new molecules with antimicrobial activity have been described, including peptides from a multitude of species [12,13], natural extracts from plants, herbs, and spices [14], polymers modified with antimicrobial functional groups [15], and metal-based molecules [16]

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