Dinuclear silver(<scp>i</scp>) complexes with a pyridine-based macrocyclic type of ligand as antimicrobial agents against clinically relevant species: the influence of the counteranion on the structure diversification of the complexes

Savić, Nada D.; Petković, Branka B.; Vojnović, Sandra; Mojićević, Marija; Wadepohl, Hubert; Olaifa, Kayode; Marsili, Enrico; Nikodinovic-Runic, Jasmina; Djuran, Miloš I.; Glišić, Biljana Đ.

doi:10.1039/d0dt01272f

Cited by 19 publications

(13 citation statements)

References 104 publications

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“…Silver compounds, free or weakly bound silver ions as well as silver nanoparticles have all been shown to be good antibacterial agents. [74][75][76][77][78] On the other hand there have been comparatively very few studies into the antifungal properties of silver complexes [79][80][81] , most of which focus on the use of silver nanoparticles. [82][83] Compounds Ag1 and Ag2 are interesting as they show exclusive antifungal activity, with no inhibition of bacterial growth observed in our assays.…”

Section: Resultsmentioning

confidence: 99%

Metal Complexes as Antifungals? – From a Crowd-Sourced Compound Library to First In Vivo Experiments

Frei

Elliott

Kan

et al. 2022

Preprint

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There are currently fewer than ten antifungal drugs in clinical development, but new fungal strains, which are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains, compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties at similar concentrations. The structures of 21 metal complexes which display high antifungal activity (MIC ≤ 1.25 µM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been evaluated for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larvae model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

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Section: Resultsmentioning

confidence: 99%

Metal Complexes as Antifungals? – From a Crowd-Sourced Compound Library to First In Vivo Experiments

Frei

Elliott

Kan

et al. 2022

Preprint

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“…15F. [15][16][17] Savic et al 82 and Olaifa et al 83 recently used electrochemical methods to test the effect of synthesized silver complexes on A. baumannii and C. albicans biofilms, respectively. A high anodic current output in both experiments decreased upon biofilm treatment with the Ag-complex as shown in Fig.…”

Section: Alternative Strategies For Targeting Biofilmsmentioning

confidence: 99%

Nanotechnologies for control of pathogenic microbial biofilms

et al. 2022

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“…In addition, coordination of different ligands to Ag(I) ions can achieve the prolonged release of Ag(I) ions at the site of infection to combat certain infections. Silver(I) complexes have been proven to exhibit antibacterial [23][24][25][26], antifungal [27][28][29][30] and anticancer [31][32][33][34][35][36][37] properties that are better than those of the free ligand.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Spectroscopy, Single-Crystal Structure Analysis and Antibacterial Activity of Two Novel Complexes of Silver(I) with Miconazole Drug

Stryjska

Korona-Głowniak

Chęcińska

et al. 2021

IJMS

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In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)2NO3 (1)] and [Ag(MCZ)2ClO4 (2)] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF4− (3), SbF6− (4)). The novel silver(I) complexes were characterized by elemental analysis, 1H NMR, 13C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.

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Dinuclear silver(i) complexes with a pyridine-based macrocyclic type of ligand as antimicrobial agents against clinically relevant species: the influence of the counteranion on the structure diversification of the complexes

Cited by 19 publications

References 104 publications

Metal Complexes as Antifungals? – From a Crowd-Sourced Compound Library to First In Vivo Experiments

Metal Complexes as Antifungals? – From a Crowd-Sourced Compound Library to First In Vivo Experiments

Nanotechnologies for control of pathogenic microbial biofilms

Synthesis, Spectroscopy, Single-Crystal Structure Analysis and Antibacterial Activity of Two Novel Complexes of Silver(I) with Miconazole Drug

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