Antimicrobial Features of Organic Functionalized Graphene-Oxide with Selected Amines

(1) Background: Graphene oxide is a new carbon-based material that contains functional groups (carboxyl, hydroxyl, carbonyl, epoxy) and therefore can be easily functionalized with organic compounds of interest, yielding hybrid materials with important properties and applications. (2) Methods: Graphene oxide has been obtained by a modified Hummers method and activated by thionyl chloride in order to be covalently functionalized with amines. Thus obtained hybrid materials were characterized by infrared and Raman spectroscopy, elemental analysis and scanning electron microscopy and then tested for their antimicrobial and anti-biofilm activity. (3) Results: Eight amines of interest were used to functionalize grapheme oxide and the materials thus obtained were tested against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacterial strainsin plankonic and biofilm growth state. Both amines, as well as the functionalized materials, exhibited anti-microbial features. Three to five functionalized graphene oxide materials exhibited improved inhibitory activity against planktonic strains as compared with the respective amines. In exchange, the amines alone proved generally more efficient against biofilm-embedded cells. (4) Conclusions: Such hybrid materials may have a wide range of potential use in biomedical applications

SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY EVALUATION ON ZINC DOPED HYDROXYAPATITE IN COLLAGEN MATRIX

International audienceThe goal of this study was to obtain at low temperature a functional nano-composite with characteristics similar to the natural bone by using a cost effective method. The structure and morphology of collagen coated zinc doped hydroxyapatite bio-composites (Zn:HAp-CBc) were examined by X-Ray diffraction (XRD) and Scanning Electron Microscopy (SEM). XRD analysis revealed that the unique hexagonal Ca 10 (PO 4) 6 (OH) 2 in P 63m space group was observed in the obtained nanocomposites Zn:HAp-CBc. The cytotoxicity of the Zn:HAp-CBc was studied on HeLa cell lines. Cell cycle distribution after treatment was examined by flow cytometry analysis. Our preliminary in vitro studies revealed that the obtained composites based on Zn doped HAp embedded in collagen matrix have excellent biocompatibility and support their further characterization by in vivo approaches and development as a biomaterial used in bone regeneration

Insights into the physico-chemical and biological characterization of sodium lignosulfonate - silver nanosystems designed for wound management

Chronic wounds represent one of the complications that might occur from the disruption of wound healing process. Recently, there has been a rise in interest in employing nanotechnology to develop novel strategies for accelerating wound healing. The aim of the present study was to use a green synthesis method to obtain AgNPs/NaLS systems useful for wounds management and perform an in-depth investigation of their behavior during and post-synthesis as well as of their biological properties. The colloids obtained from silver nanoparticles (AgNPs) and commercial sodium lignosulfonate (NaLS) in a single-pot aqueous procedure have been fully characterized by UV–Vis, FT-IR, DLS, TEM, XRD, and XPS to evaluate the synthesis efficiency and to provide new insights in the process of AgNPs formation and NaLS behavior in aqueous solutions. The effects of various concentrations of NaLS (0–16 mg/mL) and AgNO3 (0–20 mM) and of two different temperatures on AgNPs formation have been analyzed. Although the room temperature is feasible for AgNPs synthesis, the short mixing at 70 °C significantly increases the speed of nanoparticle formation and storage stability. In all experimental conditions AgNPs of 20–40 nm in size have been obtained. The antimicrobial activity assessed quantitatively on clinical and reference bacterial strains, both in suspension and biofilm growth state, revealed a broad antimicrobial spectrum, the most intensive inhibitory effect being noticed against Pseudomonas aeruginosa and Escherichia coli strains. The AgNP/NaLS enhanced the NO extracellular release, potentially contributing to the microbicidal and anti-adherence activity by protein oxidation. Both AgNP/NaLS and NaLS were non-hemolytic (hemolytic index<5%, 2.26 ± 0.13% hemolysis) and biocompatible (102.17 ± 3.43 % HaCaT cells viability). The presence of AgNPs increased the antioxidative activity and induced a significant cytotoxicity on non-melanoma skin cancer cells (62.86 ± 8.27% Cal-27 cells viability). Taken together, all these features suggest the multivalent potential of these colloids for the development of novel strategies for wound management, acting by preventing infection-associated complications and supporting the tissue regeneration

Design, Synthesis and In Vitro Characterization of Novel Antimicrobial Agents Based on 6-Chloro-9H-carbazol Derivatives and 1,3,4-Oxadiazole Scaffolds

In this paper, we aimed to exploit and combine in the same molecule the carbazole and the 1,3,4-oxadiazole pharmacophores, to obtain novel carprofen derivatives, by using two synthesis pathways. For the first route, the following steps have been followed: (i) (RS)-2-(6-chloro-9H-carbazol-2-yl)propanonic acid (carprofen) treatment with methanol, yielding methyl (RS)-2-(6-chloro-9H-carbazol-2-yl)propanoate; (ii) the resulted methylic ester was converted to (RS)-2-(6-chloro-9H-carbazol-2-yl)propane hydrazide (carprofen hydrazide) by treatment with hydrazine hydrate; (iii) reaction of the hydrazide derivative with acyl chlorides led to N-[(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanoil]-N&prime;-R-substituted-benzoylhydrazine formation, which; (iv) in reaction with phosphorus oxychloride gave the (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-(1,3,4-oxadiazol-2-yl)ethane derivatives. In the second synthesis pathway, new 1,3,4-oxadiazole ring compounds were obtained starting from carprofen which was reacted with isoniazid, in the presence of phosphorus oxychloride to form (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-[5-(4-pyridyl)-1,3,4-oxadiazol-2-yl]ethane. The synthesized compounds were characterized by IR, 1H-NMR and 13C-NMR, screened for their drug-like properties and evaluated for in vitro cytotoxicity and antimicrobial activity. The obtained compounds exhibited a good antimicrobial activity, some of the compounds being particularly active on E. coli, while others on C. albicans. The most significant result is represented by their exceptional anti-biofilm activity, particularly against the P. aeruginosa biofilm. The cytotoxicity assay revealed that at concentrations lower than 100 &mu;g/mL, the tested compounds do not induce cytotoxicity and do not alter the mammalian cell cycle. The new synthesized compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral absorption and average permeability through the blood brain barrier. However, further research is needed to reduce the predicted mutagenic potential and the hepatotoxicity

Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands

In an attempt to increase the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold through complexation with essential metal ions, the complexes trans-[Cu(mptp)2Cl2] (1), [Zn(mptp)Cl2(DMSO)] (2) (mptp: 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine), [Cu2(dmtp)4Cl4]&middot;2H2O (3) and [Zn(dmtp)2Cl2] (4) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized as new antiproliferative and antimicrobial species. Both complexes (1) and (2) crystallize in the P21/n monoclinic space group, with the tetrahedral surroundings generating a square-planar stereochemistry in the Cu(II) complex and a tetrahedral stereochemistry in the Zn(II) species. The mononuclear units are interconnected in a supramolecular network through &pi;&ndash;&pi; interactions between the pyrimidine moiety and the phenyl ring in (1) while supramolecular chains resulting from C-H&#8729;&#8729;&#8729;&pi; interactions were observed in (2). All complexes exhibit an antiproliferative effect against B16 tumor cells and improved antibacterial and antifungal activities compared to the free ligands. Complex (3) displays the best antimicrobial activity against all four tested strains, both in the planktonic and biofilm-embedded states, which can be correlated to its stronger DNA-binding and nuclease-activity traits

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp—both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide

Fish Bone Derived Bi-Phasic Calcium Phosphate Coatings Fabricated by Pulsed Laser Deposition for Biomedical Applications

We report on new biomaterials with promising bone and cartilage regeneration potential, from sustainable, cheap resources of fish origin. Thin films were fabricated from fish bone-derived bi-phasic calcium phosphate targets via pulsed laser deposition with a KrF * excimer laser source (&lambda; = 248 nm, &tau;FWHM &le; 25 ns). Targets and deposited nanostructures were characterized by SEM and XRD, as well as by Energy Dispersive X-ray (EDX) and FTIR spectroscopy. Films were next assessed in vitro by dedicated cytocompatibility and antimicrobial assays. Films were Ca-deficient and contained a significant fraction of &beta;-tricalcium phosphate apart from hydroxyapatite, which could contribute to an increased solubility and an improved biocompatibility for bone regeneration applications. The deposited structures were biocompatible as confirmed by the lack of cytotoxicity on human gingival fibroblast cells, making them promising for fast osseointegration implants. Pulsed laser deposition (PLD) coatings inhibited the microbial adhesion and/or the subsequent biofilm development. A persistent protection against bacterial colonization (Escherichia coli) was demonstrated for at least 72 h, probably due to the release of the native trace elements (i.e., Na, Mg, Si, and/or S) from fish bones. Progress is therefore expected in the realm of multifunctional thin film biomaterials, combining antimicrobial, anti-inflammatory, and regenerative properties for advanced implant coatings and nosocomial infections prevention applications

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2′-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp—both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide

Successful Release of Voriconazole and Flavonoids from MAPLE Deposited Bioactive Surfaces

We explored the potential of biomimetic thin films fabricated by means of matrix-assisted pulsed laser evaporation (MAPLE) for releasing combinations of active substances represented by flavonoids (quercetin dihydrate and resveratrol) and antifungal compounds (amphotericin B and voriconazole) embedded in a polyvinylpyrrolidone biopolymer; the antifungal activity of the film components was evaluated using in vitro microbiological assays. Thin films were deposited using a pulsed KrF* excimer laser source which were structurally characterized using atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR). High-quality thin films with chemical structures similar to dropcast ones were created using an optimum laser fluence of ~80 mJ/cm2. Bioactive substances were included within the polymer thin films using the MAPLE technique. The results of the in vitro microbiology assay, which utilized a modified disk diffusion approach and were performed using two fungal strains (Candida albicans American Type Culture Collection (ATCC) 90028 and Candida parapsilosis American Type Culture Collection (ATCC) 22019), revealed that voriconazole was released in an active form from the polyvinylpyrrolidone matrix. The results of this study show that the MAPLE-deposited bioactive thin films have a promising potential for use in designing combination products and devices, such as drug delivery devices, and medical device surfaces with antifungal activity