Exploiting bacterial DNA gyrase as a drug target: current state and perspectives

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme

Probing the binding of the coumarin drugs using peptide fragments of DNA gyrase B protein

Bacterial DNA gyrase, has been identified as the target of several antibacterial agents, including the coumarin drugs. The coumarins inhibit the gyrase action by competitive binding to the ATP-binding site of DNA gyrase B (GyrB) protein. The high in vitro inhibitory potency of coumarins against DNA gyrase reactions has raised interest in studies on coumarin-gyrase interactions. In this context, a series of low-molecular weight peptides, including the coumarin resistance-determining region of subunit B of Escherichia coli gyrase, has been designed and synthesized. The first peptide model was built using the natural fragment 131-146 of GyrB and was able to bind to novobiocin (K a = 1.8 ± 0.2 × 105/M) and ATP (Ka = 1.9 ± 0.4 × 103/M). To build the other sequences, changes in the Arg136 residue were introduced so that the binding to the drug was progressively reduced with the hydrophobicity of this residue (Ka = 1.3 ± 0.1 × 105/M and 1.0 ± 0.2 × 105/M for Ser and His, respectively). No binding was observed for the change Arg136 to Leu. In contrast, the binding to ATP was not altered, independently of the changes promoted. On the contrary, for peptide-coumarin and peptide-ATP complexes, Mg2+ appears to modulate the binding process. Our results demonstrate the crucial role of Arg 136 residue for the stability of coumarin-gyrase complex as well as suggest a different binding site for ATP and in both cases the interactions are mediated by magnesium ions. Copyright Blackwell Munksgaard, 2005

Sustainable nanocomposite films based on bacterial cellulose and pullulan

Bionanocomposites with improved properties based on two microbial polysaccharides, pullulan and bacterial cellulose, were prepared and characterized. The novel materials were obtained through a simple green approach by casting water-based suspensions of pullulan and bacterial cellulose and characterized by TGA, RDX, tensile assays, SEM and AFM. The effect of the addition of glycerol, as a plasticizer, on the properties of the materials was also evaluated. All bionanocomposites showed considerable improvement in thermal stability and mechanical properties, compared to the unfilled pullulan films, evidenced by the significant increase in the degradation temperature (up to 40 A degrees C) and on both Young's modulus and tensile strength (increments of up to 100 and 50%, for films without glycerol and up to 8,000 and 7,000% for those plasticized with glycerol). Moreover, these bionanocomposite films are highly translucent and could be labelled as sustainable materials since they were prepared entirely from renewable resources and could find applications in areas as organic electronics, dry food packaging and in the biomedical field

Topical caffeine delivery using biocellulose membranes: a potential innovative system for cellulite treatment

In this study, biocellulose (BC) membranes have been investigated as caffeine topical delivery systems, for the potential treatment of cellulite. BC-caffeine membranes were prepared by a simple approach and the permeation of caffeine through human epidermis, from BC or from conventional formulation systems (solution and gel), was compared in vitro to assess their therapeutic applicability. Diffusion studies with Franz cells showed that the incorporation of caffeine in BC membranes provided lower permeation rates than those obtained with the conventional formulations. These results combined with the possibility of producing BC membranes with different shapes demonstrate that these materials are promising biosystems for topical delivery of caffeine, showing reproducibility and an extended and predictable caffeine release over time, leading to their potential use for cellulite attenuation

Effect of cellulose nanofiber dimensions on sheet forming through filtration

Four different cellulose nanofibers samples were prepared from northern bleached softwood kraft fibers. Fiber diameter distributions were measured from SEM images. Fiber aspect ratios ranging from 84 to 146 were estimated from fiber suspension sedimentation measurements. Three samples had heterogeneous distributions of fiber diameters, while one sample was more homogeneous. Sheet forming experiments using filters with pores ranging from 150 to 5 μm showed that the samples with a heterogeneous distribution of fiber dimensions could be easily formed into sheets at 0. 2% initial solids concentration with all filter openings. On the other hand, sheets could only be formed from the homogenous sample by using 0. 5% or more initial solids content and a lower applied vacuum and smaller filter openings. The forming data and estimated aspect ratios show reasonable agreement with the predictions of the crowding number and percolation theories for the connectivity and rigidity thresholds for fiber suspensions

Pharmacological Basis for Traditional Use of the Lippia thymoides

Submitted by Adagilson Silva ([email protected]) on 2017-11-23T13:14:56Z No. of bitstreams: 1 25892998 2015 sil-pha.oa.pdf: 923236 bytes, checksum: efa491ede009552b43fec1338e6363ed (MD5)Approved for entry into archive by Adagilson Silva ([email protected]) on 2017-11-27T14:40:31Z (GMT) No. of bitstreams: 1 25892998 2015 sil-pha.oa.pdf: 923236 bytes, checksum: efa491ede009552b43fec1338e6363ed (MD5)Made available in DSpace on 2017-11-27T14:40:31Z (GMT). No. of bitstreams: 1 25892998 2015 sil-pha.oa.pdf: 923236 bytes, checksum: efa491ede009552b43fec1338e6363ed (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, BrasilThe aim of this study was to evaluate crude extracts and fractions from leaves and stems of Lippia thymoides and to validate their use in folk medicine. In vitro antioxidant and antimicrobial activities and in vivo wound healing in rats, baker yeast-induced fever in young rats, and acute oral toxicity in mice assays were realized. The crude extracts and their dichloromethane and ethyl acetate fractions had potent radical-scavenging activity against the DPPH but were not effective in the β-carotene bleaching method. The dichloromethane fraction from the leaves extract showed the broadest spectrum of activity against S. aureus, B. cereus, and C. parapsilosis. The animals treated with crude extracts showed no difference in wound healing when compared with the negative control group. The crude extract from leaves (1200 mg/kg) has equal efficacy in reducing temperature in rats with hyperpyrexia compared to dipyrone (240 mg/kg) and is better than paracetamol (150 mg/kg). In acute toxicity test, crude extract of leaves from Lippia thymoides exhibited no mortality and behavioral changes and no adverse effects in male and female mice. This work validates the popular use of Lippia thymoides for treating the wound and fever, providing a source for biologically active substances

Cellulose/iron oxide hybrids as multifunctional pigments in thermoplastic starch based materials

Cellulose/iron oxide hybrids were prepared by the controlled hydrolysis of FeC2O4 in the presence of vegetable and bacterial cellulose fibres as substrates. By varying the relative amount of FeC2O4 and NaOH, either hematite or magnetic iron oxides were grown at the cellulose fibres surfaces. This chemical strategy was used for the production of a number of materials, whose coloristic properties associated to their reinforcement role allowed their use as new hybrid pigments for thermoplastic starch (TPS) based products. The TPS reinforced materials were characterized by several techniques in order to evaluate: the morphology and the compatibility between the matrix and the fillers; the mechanical reinforcement effect of the cellulose/iron oxide pigments on TPS and the coloristic properties of the composites. All materials showed good dispersion and strong adhesion for the cellulose/iron oxide nanocomposites in the TPS matrix thus resulting in improved mechanical properties