Antimicrobial Activity of Silver Camphorimine Complexes against Candida Strains

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.

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“…The bacterial and fungal strains were isolated from human infections [30][31][32][33]. When in use, bacterial strains were maintained in Lennox Broth (LB) solid medium (10 g/L tryptone, 5 g/L yeast extract, 5 g/L NaCl and 15 g/L agar), while fungal strains were maintained in Yeast Extract-Peptone-Dextrose (YPD) solid medium (20 g/L glucose, 20 g/L peptone, 10 g/L yeast extract and 15 g/L agar), as previously described [34].…”

“…Antifungal susceptibility testing was carried out according to the standardized microdilution method recommended by EUCAST (European Committee on Antimicrobial Susceptibility Testing) for Candida spp. [48], and as previously described [34,49] [47]. In each experiment, positive (without compound) and negative controls (no organism inoculum) were carried out.…”

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“…MIC values were experimentally determined in a 96 well plate using RPMI 1640 medium (Sigma) containing 20 g/L glucose (final concentration), and buffered to pH 7.0 with 0.165 M morpholine propane sulphonic acid (MOPS; SIGMA) using the broth microdilution method recommended by EUCAST (European Committee on Antimicrobial Susceptibility Testing) for Candida spp. [92], and as previously described [9,93]. The extracts were sequentially 1:2 diluted in order to obtain final concentrations ranging between 0.23 and 2000 µg/mL.…”

“…Furthermore, emerging resistance to the available antifungal drugs has been reported, in particular to azole and echinocandins, due to clinical and environment exposure [8]. Therefore, novel antifungal drugs or adjuvants that lower the quantities of antifungals to achieve eradication of infection with lower toxicity are urgently required [9].…”

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“…Articles on in vitro work by Vianna et al [18] on antimicrobial efflux pumps and Costa et al [19] outlining the antimicrobial activity of silver camphro-imine complexes alongside work from Gavilán et al [20] on a novel and sensitive assay for detecting low levels of antibiotic in animal feed, complete this innovative and exciting multi-disciplinary issue of Antibiotics.…”