Aleksandra Felczak

Biological properties of new viologen-phosphorus dendrimers.

Some biological properties of eight dendrimers incorporating both phosphorus linkages and viologen units within their cascade structure or at the periphery were investigated for the first time. In particular cytotoxicity, hemotoxicity, and antimicrobial and antifungal activity of these new macromolecules were examined. Even if for example all these species exhibited good antimicrobial properties, it was demonstrated that their behavior strongly depends on several parameters as their size and molecular weight, the number of viologen units and the nature of the terminal groups.

Antimicrobial activity of poly(propylene imine) dendrimers

Poly(propylene imine) dendrimers have been investigated for their biological applications but their antibacterial activity has not been extensively explored. Thus, the fourth generation of poly(propylene imine) dendrimers (PPI-G4) and PPI dendrimers with a surface modified by attaching maltose in 25% and 100% (PPI-25%mG4 and PPI-100%mG4, respectively) was evaluated for the antibacterial activity against Gram-positive bacteria: Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Gram-negative bacteria: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 15442 and yeast Candida albicans ATCC 10231. Cytotoxicity of all tested dendrimers was checked on a Chinese hamster fibroblast cell line (B14), human liver hepatocellular carcinoma cell line (HepG2), mouse neuroblastoma cell line (N2a) and rat liver cell line (BRL-3A). The obtained results indicate that studied nano-sized macromolecules possess the greatest antimicrobial activity against S. aureus. PPI G4 dendrimers modified with 25% of maltose display antibacterial activity and a striking selectivity toward S. aureus, at the concentrations, which are at the same time harmless for the eukaryotic cell lines. Moreover, at the higher concentrations of unmodified dendrimers efficient growth inhibition of S. epidermidis and C. albicans has been observed.

Surface area or diameter – which factor really determines the antibacterial activity of silver nanoparticles grown on TiO2 coatings?

Titanium dioxide coatings were prepared on Si wafers using the sol–gel method. Four different types of coatings with silver nanoparticles (AgNPs) were synthesized. The diameter and surface density of AgNPs were conditioned by the concentration of Ag+ ions in the initial solution, time and UV illumination source. The bactericidal activity of AgNPs on the titanium dioxide coatings against the S. aureus strain were calculated as the percentage of the inhibition of bacterial growth after 24 hour incubation of microorganisms at 37 °C on TiO2 coatings with AgNPs. Control samples were coated with titanium dioxide without AgNPs. We concluded that the titanium dioxide coatings modified with silver nanoparticles had a high antibacterial activity. Moreover, we demonstrated strong dependence between surface areas of AgNPs and inhibition of bacterial growth. The obtained results evidence that the surface area of AgNPs grown on titanium dioxide coatings is a major factor determining their antimicrobial potential.

Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6-di(CH2OH)py)2]NO3

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.

The antibacterial effect of the co-administration of poly(propylene imine) dendrimers and ciprofloxacin

Fluoroquinolones, including ciprofloxacin, are often used to treat bacterial diseases. Due to the spread of drug resistance among microorganisms, alternative treatments are being sought. We report here on the antimicrobial activity of generation 4 (G4) PPI dendrimers in the presence of ciprofloxacin against the reference strains of Gram-positive bacterium Staphylococcus aureus ATCC 6538 and Gram-negative bacterium Escherichia coli ATCC 25922. Cytotoxicity of these compounds was investigated in the eukaryotic B14 Chinese hamster fibroblast cell line, HepG2 human liver hepatocellular carcinoma cell line, mouse neuroblastoma N2a cell line and BRL-3A rat liver cell line. For both strains, the administration of PPI dendrimers along with ciprofloxacin significantly improved its antibacterial effect compared to the cultures given the drug alone. The simultaneous application of dendrimers and ciprofloxacin shows the opportunity of using it at lower doses. Ciprofloxacin and PPI dendrimers are harmful to bacterial strains at the concentrations non-toxic to the eukaryotic cells.

Enhancement of antimicrobial activity by co-administration of poly(propylene imine) dendrimers and nadifloxacin

Despite the studies of dendrimers for biomedical application, the antibacterial activity of dendrimers has not been extensively explored. In the presented study we evaluate the antimicrobial activity of poly(propylene imine) dendrimers (PPI-G4) and their derivatives modified with maltose (PPI-25%mG4) in combination with nadifloxacin against Gram-negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 15442 and Proteus hauseri ATCC 13315. Cytotoxicity of all studied dendrimers and nadifloxacin was investigated in a Chinese hamster fibroblast cell line (B14), a human liver hepatocellular carcinoma cell line (HepG2), a mouse neuroblastoma cell line (N2a) and a rat liver cell line (BRL-3A). The obtained results indicate that co-administration of nadifloxacin and studied dendrimers enhances the antimicrobial activity of the antibiotic against Gram-negative bacteria, at concentrations that are at the same time harmless to the eukaryotic cell lines. Moreover, the contribution of dendrimers allows using lower doses of the antibiotic.

Poly(Propylene Imine) Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine) (PPI) dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3). The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin.

Influence of selected inorganic counter-ions on the structure and antimicrobial properties of silver(I) complexes with imidazole-containing ligands

Water-soluble silver(I) complexes containing the 4(5)-(hydroxymethyl)imidazole ligand with the formula [Ag(4-CH2OHimH)2]X (where X = NO3−, ClO4−, CF3COO−, BF4− and SO3CH3−) were synthesized. The complexes were characterized by NMR (1H and 13C) and IR spectroscopy, ESI-MS spectrometry and EA. The molecular structures of three complexes were confirmed by X-ray crystallography. The antimicrobial activity of the silver(I) complexes were evaluated against six strains of microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Proteus hauseri and Candida albicans. All tested silver complexes displayed excellent antibacterial properties against Gram-positive bacteria. Among them, the complex containing the trifluoroacetate counter-ion exhibited the highest antibacterial activity, with MIC values 2 to 3-fold lower than that required by silver sulfadiazine.

Quinoline biodegradation by filamentous fungus Cunninghamella elegans and adaptive modifications of the fungal membrane composition.

Quinoline, which belongs to N-heterocyclic compounds, occurs naturally in the environment and is used in numerous industrial processes. The structures of various chemicals, such as dyes and medicines, are based on this compound. Due to that fact, quinoline and its derivatives are widely distributed in environment and can exert toxic effects on organisms from different trophic levels. The ability of the filamentous fungus Cunninghamella elegans IM 1785/21Gp to degrade quinoline and modulate the membrane composition in response to the pollutant was studied. C. elegans IM 1785/21Gp removes quinoline with high efficiency and transforms the pollutant into two novel hydroxylated derivatives, 2-hydroxyquinoline and 3-hydroxyquinoline. Moreover, due to the disruption in the membrane stability by quinoline, C. elegans IM 1785/21Gp modulates the fatty acid composition and phospholipid profile.

Oleochemical‐Tethered SBA‐15‐Type Silicates with Tunable Nanoscopic Order, Carboxylic Surface, and Hydrophobic Framework: Cellular Toxicity, Hemolysis, and Antibacterial Activity

Novel silicates were prepared by using silylated natural fatty acids (derived from triglyceride renewable oils) as co-condensing reagents in presence of tetraethyl orthosilicate (TEOS) and the triblock copolymer, pluronic P123, as a structure directing agent. A series of carboxylic acid functionalized SBA-15-type mesoporous silicates were obtained with tunable nanoscopic order and reactive functional groups that allow the conjugation of amino probes by peptide coupling. Photophysical studies of the covalently linked aminopyrene substantiated that the internal framework of these materials have pronounced hydrophobicity. Moreover, phase separation that can emanate from the bulkiness of the starting fatty silanes has been ruled out owing to the absence of excimers after aminopyrene grafting. The hemotoxicity, cytotoxicity, and antimicrobial activity of these novel silicates were then evaluated. Without discrimination, the functionalized silicates show a significant decrease of red blood cell hemolysis as compared to bare SBA-15-silica material. Within the modified silicate series, germanium-free mesoporous silicates induce only a slight decrease in cell viability and, more interestingly, they exhibit negligible hemolytic effect. Moreover, increasing their concentration in the medium reduces the concentration of released hemoglobin as a result of Hb adsorption. Promising antimicrobial properties were also observed for these silicates with a slight dependency on whether phenylgermanium fragments were present within the silicate framework.