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Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)2AgNO3], [(MTZ)2Ag]2SO4, [Ag(MCZ)2NO3], [Ag(MCZ)2BF4], [Ag(MCZ)2SbF6] and [Ag(MCZ)2ClO4] (MTZ—metronidazole; MCZ—miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC50 values against the A375 line were demonstrated by [Ag(MCZ)2NO3] and [(MTZ)2AgNO3]. The compound [(MTZ)2AgNO3] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L. [ABSTRACT FROM AUTHOR]

Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH3-substituted thiadiazole-based thioamide 5-methyl-1,3,4-thiadiazole-2-thiol (mtdztH) and phosphines, i.e., [AgCl(mtdztH)(PPh3)2] (1), [Ag(mtdzt)(PPh3)3] (2), [AgCl(mtdztH)(xantphos)] (3), and [AgmtdztH)(dppe)(NO3)]n (4), where xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and dppe = 1,2-bis(diphenylphosphino)ethane, and the assessment of their in vitro antibacterial and anti-cancer efficiency. Among them, diphosphine-containing compounds 3 and 4 were found to exhibit broad-spectrum antibacterial activity characteristics against both Gram-(+) and Gram-(–) bacterial strains, showing high in vitro bioactivity with IC50 values as low as 4.6 μΜ. In vitro cytotoxicity studies against human ovarian, pancreatic, lung, and prostate cancer cell lines revealed the strong cytotoxic potential of 2 and 4, with IC50 values in the range of 3.1–24.0 μΜ, while 3 and 4 maintained the normal fibroblast cells' viability at relatively higher levels. Assessment of these results, in combination with those obtained for analogous Ag(I) complexes bearing similar heterocyclic thioamides, suggest the pivotal role of the substituent groups of the thioamide heterocyclic ring in the antibacterial and anti-cancer efficacy of the respective Ag(I) complexes. Compounds 1–4 exhibited moderate in vitro antioxidant capacity for free radicals scavenging, as well as reasonably strong ability to interact with calf-thymus DNA, suggesting the likely implication of these properties in their bioactivity mechanisms. Complementary insights into the possible mechanism of their anti-cancer activity were provided by molecular docking calculations, exploring their ability to bind to the overexpressed fibroblast growth factor receptor 1 (FGFR1), affecting cancer cells' functionalities. [ABSTRACT FROM AUTHOR]

Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44-28.65 μM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis. [ABSTRACT FROM AUTHOR]

Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44-28.65 μM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis. [ABSTRACT FROM AUTHOR]

Six silver(I) coordination complexes have been prepared and structurally characterised. Mixed chalcogen-donor acenaphthene ligands L1-L3 [Acenap(EPh)(E'Ph)] (Acenap = acenaphthene-5,6-diyl; E/E' = S, Se, Te) were independently treated with silver(I) salts (AgBF4/AgOTf). In order to keep the number of variables to a minimum, all reactions were carried out using a 1:1 ratio of Ag/L and run in dichloromethane. The nature of the donor atoms, the coordinating ability of the respective counter-anion and the type of solvent used in recrystallisation, all affect the structural architecture of the final silver(I) complex, generating monomeric, silver(I) complexes {[AgBF4(L)2] (1 L = L1; 2 L = L2; 3 L = L3), [AgOTf(L)3] (4 L = L1; 5 L = L3), [AgBF4(L)3] (2a L = L1; 3a L = L3)} and a 1D polymeric chain {[AgOTf(L3)]n 6}. The organic acenaphthene ligands L1-L3 adopt a number of ligation modes (bis-monodentate μ2-η2-bridging, quasi-chelating combining monodentate and η6-E(phenyl)-Ag(I) and classical monodentate coordination) with the central silver atom at the centre of a tetrahedral or trigonal planar coordination geometry in each case. The importance of weak interactions in the formation of metal-organic structures is also highlighted by the number of short non-covalent contacts present within each complex. [ABSTRACT FROM AUTHOR]

Simple Summary: Our previous studies demonstrated that a silver(I) nitrate complex with metronidazole presented greater photo-stability, antimicrobial, cytotoxic and genotoxic properties than silver(I) nitrate. These advantages make the complex a better candidate for clinical therapy than pure salt. Therefore, in this study, we decided to synthetize and determine the chemical, cytotoxic and antimicrobial properties of [Ag(MTZ)2]2SO4, a novel metronidazole silver(I) complex, in comparison with pure salt Ag2SO4 and [Ag(MTZ)2NO3]. The photo-stability, cytotoxicity toward cancer cells and antimicrobial activity of [Ag(MTZ)2]2SO4 is higher than Ag2SO4. What is more, we found that the novel synthetized complex shows better cytotoxicity against cancer cells than [Ag(MTZ)2NO3]. Both complexes have similar biological activity against the majority of tested bacterial strains. Silver salts and azole derivatives are well known for their antimicrobial properties. Recent evidence has demonstrated also their cytotoxic and genotoxic potential toward both normal and cancer cells. Still, little is known about the action of complexes of azoles with silver(I) salts. Thus, the goal of the study was to compare the chemical, cytotoxic and antimicrobial properties of metronidazole complexes with silver(I) nitrate and silver(I) sulfate to metronidazole and pure silver(I) salts. We synthetized a novel complex, [Ag(MTZ)2]2SO4, and confirmed its chemical structure and properties using 1H and 13C NMR spectroscopy and X-Ray, IR and elemental analysis. To establish the stability of complexes [Ag(MTZ)2NO3] and [Ag(MTZ)2]2SO4, they were exposed to daylight and UV-A rays and were visually assessed. Their cytotoxicity toward human cancer cells (HepG2, Caco-2) and mice normal fibroblasts (Balb/c 3T3 clone A31) was determined by MTT, NRU, TPC and LDH assays. The micro-dilution broth method was used to evaluate their antimicrobial properties against Gram-positive and Gram-negative bacteria. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy. The photo-stability of the complexes was higher than silver(I) salts. In human cancer cells, [Ag(MTZ)2]2SO4 was more cytotoxic than Ag2SO4 and, in turn, AgNO3 was more cytotoxic than [Ag(MTZ)2NO3]. For Balb/c 3T3 cells, Ag2SO4 was more cytotoxic than [Ag(MTZ)2]2SO4, while the cytotoxicity of AgNO3 and [Ag(MTZ)2NO3] was similar. Metronidazole in the tested concentration range was non-cytotoxic for both normal and cancer cells. The complexes showed increased bioactivity against aerobic and facultative anaerobic bacteria when compared to metronidazole. For the majority of the tested bacterial strains, the silver(I) salts and complexes showed a higher antibacterial activity than MTZ; however, some bacterial strains presented the reverse effect. Our results showed that silver(I) complexes present higher photo-stability, cytotoxicity and antimicrobial activity in comparison to MTZ and, to a certain extent, to silver(I) salts. [ABSTRACT FROM AUTHOR]

Three silver(I) dipeptide complexes [Ag(GlyGly)]n(NO3)n (AgGlyGly), [Ag2(GlyAla)(NO3)2]n (AgGlyAla) and [Ag2(HGlyAsp)(NO3)]n (AgGlyAsp) were prepared, investigated and characterized by vibrational spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 μM. [ABSTRACT FROM AUTHOR]

Three new silver(I) complexes [Ag(NO3)(tia)(H2O)]n (Ag1), [Ag(CF3SO3)(1,8-naph)]n (Ag2) and [Ag2(1,8-naph)2(H2O)1.2](PF6)2 (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56–7.81 μg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1–3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A series of neutral mixed-ligand [HB(pz)3]Ag(PR3) silver(I) complexes (PR3 = tertiary phosphine, [HB(pz)3]− = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR3)4]BF4 compounds have been synthesized and fully characterized. Silver compounds were screened for their antiproliferative activities against a wide panel of human cancer cells derived from solid tumors and endowed with different platinum drug sensitivity. Mixed-ligand complexes were generally more effective than the corresponding homoleptic derivatives, but the most active compounds were [HB(pz)3]Ag(PPh3) (5) and [Ag(PPh3)4]BF4 (10), both comprising the lipophilic PPh3 phosphine ligand. Detailed mechanistic studies revealed that both homoleptic and heteroleptic silver complexes strongly and selectively inhibit the selenoenzyme thioredoxin reductase both as isolated enzyme and in human ovarian cancer cells (half inhibition concentration values in the nanomolar range) causing the disruption of cellular thiol-redox homeostasis, and leading to apoptotic cell death. Moreover, for heteroleptic Ag(I) derivatives, an additional ability to damage nuclear DNA has been detected. These results confirm the importance of the type of silver ion coordinating ligands in affecting the biological behavior of the overall corresponding silver complexes, besides in terms of hydrophilic–lipophilic balance, also in terms of biological mechanism of action, such as interaction with DNA and/or thioredoxin reductase. [ABSTRACT FROM AUTHOR]

In previous papers, we have reported on the high antifungal and significant antibacterial activity against Gram-positive and Gram-negative bacteria of the water-soluble silver(I) complexes of metronidazole and derivatives of pyridine compared to silver nitrate. In the present study, the cytotoxic activity of the silver(I) complexes of metronidazole and 4-hydroxymethylpyridine was compared with that of silver nitrate. Metronidazole and 4-hydroxymethylpyridine were investigated using Balb/c 3T3 and HepG2 cell lines in order to evaluate the potential clinical application of silver(I) complexes. The cells were exposed for 72 h to compounds at eight concentrations. The cytotoxic concentrations (IC50) of the study compounds were assessed within four biochemical endpoints: mitochondrial activity, lysosomal activity, cellular membrane integrity, and total protein content. The investigated silver(I) complexes displayed comparable cytotoxicity to that of silver nitrate used in clinics. Mean cytotoxic concentrations calculated for investigated silver(I) complexes from concentration–response curves ranged from 2.13 to 26.5 µM. HepG2 cells were less sensitive to the tested complexes compared to fibroblasts (Balb/c 3T3). However, the most affected endpoint for HepG2 cells was cellular membrane damage. The cytotoxicity of both silver complexes was comparable for Balb/c 3T3 cells. The cytotoxic potential of the new silver(I) compounds compared to that of silver nitrate used in medicine indicates that they are safe and could be used in clinical practice. The presented results are yet more stimulating to further studies that evaluate the therapeutic use of silver complexes. [ABSTRACT FROM AUTHOR]

Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44-28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis.