Physicochemical analyses of a bioactive 4-aminoantipyrine analogue - synthesis, crystal structure, solid state interactions, antibacterial, conformational and docking studies

A novel Schiff base derivative of 4-aminoantipyrine, that is, (E)-4-(2-methoxybenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (MBA-dMPP), was synthesized and characterized by FT-IR, 1H-NMR, and EI-MS. Single-crystal X-ray diffraction data revealed MBA-dMPP adopts a trans configuration around its central C=N double bond, and forms orthorhombic crystals. XRD revealed that MBA-dMPP possess two different planes, in which the pyrazolone and benzylidene groups attached to C9 of the pyrazolone ring are almost coplanar and the phenyl ring connected to the N1 atom of the pyrazolone moiety lies in another plane. The intermolecular, host-guest C-H…O, C-H…N, and C-H…C van der Waals interactions were found to form a 3D network and confer stability to the MBA-dMPP crystal structure. The quantitative and qualitative solid state behaviors of MBA-dMPP were subjected to 3D Hirshfeld surface analysis and 2D fingerprint plotting. Reciprocal H…H contacts contributed most (52.9 %) to the Hirshfeld surface, followed by C…H/H…C contacts (30.2 %), whereas, O…H/H…O and N…H/H…N interactions contributed 15.5 % to the Hirshfeld surface. Electrostatic potentials were mapped over the Hirshfeld surface to analyze electrostatic complementarities within the MBA-dMPP crystal. In addition, geometrical descriptors were also analyzed to the extent of surface interactions. MBA-dMPP was also investigated for in vitro antibacterial activity against Gram-positive and Gram-negative bacterial strains, and showed highest activity against Bacillus cereus (MIC = 12.5 mg mL -1) and Salmonella tythimurium (MIC = 50 mg mL-1). In silico screening was conducted by docking MBA-dMPP on the active site of S12 bacterial protein (an important therapeutic target of antibacterial agents) and its binding properties were compared with those of ciprofloxacin. Moreover, a field points map of MBA-dMPP ligand was studied to determine electrostatic and van der Waals forces, hydrophobic potentials, and positions involved in ligand-receptor interactions. Finally, the torsion energies of crystal structure and optimized and bioactive conformers of MBA-dMPP were compared to predict its bioactive conformation

Eco-friendly synthesis, physicochemical studies, biological assay and molecular docking of steroidal oxime-ethers

The aim of this study was to report the synthesis of biologically active compounds; 7-(2′-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85–93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay. The binding capabilities of a compound 6 exhibiting good antibacterial potential were assessed on the basis of molecular docking studies and four types of three-dimensional molecular field descriptors. Moreover the structure–antimicrobial activity relationships were studied using some physicochemical and quantum-chemical parameters with GAMESS interface as well as WebMO Job Manager by using the basic level of theory. Hence, this synthetic approach is believed to provide a better scope for the synthesis of steroidal oxime-ether analogues and will be a more practical alternative to the presently existing procedures. Moreover, detailed in silico docking studies suggested the plausible mechanism of steroidal oxime-ethers as effective antimicrobial agents

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes glioma cell invasion through induction of NF-κB-inducing kinase (NIK) and noncanonical NF-κB signaling

BACKGROUND: High-grade gliomas are one of the most invasive and therapy-resistant cancers. We have recently shown that noncanonical NF-κB/RelB signaling is a potent driver of tumorigenesis and invasion in the aggressive, mesenchymal subtype of glioma. However, the relevant signals that induce activation of noncanonical NF-κB signaling in glioma and its function relative to the canonical NF-κB pathway remain elusive. METHODS: The ability of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to regulate NF-κB signaling and promote tumor progression was investigated in both established and primary high-grade glioma tumor lines using a three-dimensional (3-D) collagen invasion assay. The roles of specific NF-κB proteins in regulating glioma cell invasion and expression of Matrix Metalloproteinase 9 (MMP9) in response to TWEAK were evaluated using shRNA-mediated loss-of-function studies. The ability of NF-κB-inducing kinase (NIK) to promote glioma growth in vivo was investigated using an orthotopic xenograft mouse model. RESULTS: In glioma cells that display elevated noncanonical NF-κB signaling, loss of RelB attenuates invasion without affecting RelA expression or phosphorylation and RelB is sufficient to promote invasion in the absence of RelA. The cytokine TWEAK preferentially activates the noncanonical NF-κB pathway through induction of p100 processing to p52 and nuclear accumulation of both RelB and p52 without activating the canonical NF-κB pathway. Moreover, TWEAK, but not TNFα, significantly increases NIK mRNA levels. TWEAK also promotes noncanonical NFκB-dependent MMP9 expression and glioma cell invasion. Finally, expression of NIK is sufficient to increase gliomagenesis in vivo. CONCLUSIONS: Our data establish a key role for NIK and noncanonical NF-κB in mediating TWEAK-induced, MMP-dependent glioma cell invasion. The findings also demonstrate that TWEAK induces noncanonical NF-κB signaling and signal-specific regulation of NIK mRNA expression. Together, these studies reveal the important role of noncanonical NF-κB signaling in regulating glioma invasiveness and highlight the therapeutic potential of targeting activation of NIK in this deadly disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-014-0273-1) contains supplementary material, which is available to authorized users

Mesoscopic Stacking Reconfigurations in Stacked van der Waals Film

Mesoscopic-scale stacking reconfigurations are investigated when van der Waals films are stacked. We have developed a method to visualize complicated stacking structures and mechanical distortions simultaneously in stacked atom-thick films using Raman spectroscopy. In the rigid limit, we found that the distortions originate from the transfer process, which can be understood through thin film mechanics with a large elastic property mismatch. In contrast, with atomic corrugations, the in-plane strain fields are more closely correlated with the stacking configuration, highlighting the impact of atomic reconstructions on the mesoscopic scale. We discovered that the grain boundaries don`t have a significant effect while the cracks are causing inhomogeneous strain in stacked polycrystalline films. This result contributes to understanding the local variation of emerging properties from moir\'e structures and advancing the reliability of stacked vdW material fabrication.Comment: 38 pages, 23 figure

Biological and quantitative-SAR evaluations, and docking studies of (E)-N'-benzylidenebenzohydrazide analogues as potential antibacterial agents

A series of 15 (E)-N'-benzylidenebenzohydrazide analogues were evaluated for their antimicrobial activities against eleven pathogenic and food-borne microbes, namely, S. aureus (G+), L. monocytogenes (G+), B. subtilis (G+), K. pneumonia (G-), C. sakazakii (G-), C. freundii (G-), S. enterica (G-), S. enteritidis (G-), E. coli (G-), Y. pestis (G-), and P. aeruginosa (G-). Most of the compounds exhibited selective activity against some Gram-negative bacterial strains. Of the compounds tested (3a-o), 3b and 3g were most active against C. freundii (MIC = ~19 µg mL-1). Whereas, compounds 3d, 3i, 3k and 3n exhibited MIC values ranging from 37.5 to 75 µg mL-1 against C. freundii, and compounds 3e, 3l and 3n had MIC values of ~75 µg mL-1 against K. pneumonia. Quantitative structure-antibacterial activity relationships were studied using physicochemical parameters and a good correlation was found between calculated octanol-water partition coefficients (clogP; a lipophilic parameter) and antibacterial activities. In silico screening was also performed by docking high (3b and 3g) and low (3n) activity compounds on the active site of E. coli FabH receptor, which is an important therapeutic target. The findings of these in silico screening studies provide a theoretical basis for the design and synthesis of novel benzylidenebenzohydrazide analogues that inhibit bacterial FabH

Changes in activity and isozyme patterns of peroxidase and chitinase in kiwifruit pollen

In this study, changes in activity and isozyme patterns of peroxidase (POD) and chitinase in kiwifruit (Actinidia chinensis) pollen were investigated under different storage conditions. Although residual activity was detected in heat-treated pollen, changes in POD activity were observed due to difference in storage conditions as revealed by preliminary studies in which pollen germination varied with different storage conditions. POD activity of kiwifruit pollen increased as proportions of viable pollen increased, indicating a positive correlation (R2=0.993) between pollen viability and POD activity. There was a detectable difference in the relative activity of POD enzyme between heat-treated and viable pollen. Decoloration of Congo Red was observed in germination medium which fresh pollen was cultured. The activity of individual chitinase isozymes present in kiwifruit pollen differed depending on storage conditions, which had a direct impact on pollen vigor. Although direct evidence showing that chitinase isozymes are implicated in pollen vigor is still uncertain, distinction of isozymes may facilitate more precise identification of viable pollen which possesses germination potential from non-viable pollen. Taken together, these results suggest that monitoring the activity of POD and chitinase can be an attractive alternative to evaluate pollen vigor in kiwifruit

Development of Parametric Trend Life Cycle Assessment for marine SOx reduction scrubber systems

In response to the impending international maritime regulation, MARPOL Annex VI Reg. 14, to curb sulphur oxides (SOx) arising from shipping activities, this paper aimed to evaluate the environmental impacts of the entire life cycle of three different SOx reduction scrubber systems: (1) ‘wet open-loop’, (2) ‘wet closed-loop’, and (3) ‘wet hybrid’. To achieve this goal, the paper developed ‘the Parametric Trend Life Cycle Assessment (PT-LCA)’ which was introduced to proceed the extensive analysis for a number of case ship studies and quantify various emissions, such as greenhouse gases (GHG), sulphur oxides (SOx), nitrogen oxides (NOx), associated with the proposed systems from cradle to grave. A case study designed with the database consisting of 1,565 ocean-going Ro-Ro vessels based on Lloyd’s Register has revealed that, in terms of Global Warming Potential (GWP) and Acidification Potential (AP), closed-loop scrubbers were proven more environmentally friendly than open-loop scrubbers, but the opposite was true for Eutrophication Potential (EP). By identifying specific trends in scrubber systems in relation to various input parameters, the assessment contributed to improving environmental sustainability, as well as the total estimated amount of numerical environmental impacts that the scrubber systems have for the international fleets. The proposed framework enabled us not only to evaluate the different emission levels of systems applied to various ships but also to obtain the general trends of emission levels over ship parameters, which were expressed as formulae. The novelty of this paper can be placed on the provision of an insight into the optimal selection of scrubber systems depending on ship characteristics. It could also offer an insight into the improvement of current environmental regulations and guidelines by means of PT-LCA

Collagen Immobilization on Ultra-thin Nanofiber Membrane to Promote In Vitro Endothelial Monolayer Formation

The endothelialization on the poly (epsilon-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (epsilon-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (epsilon-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (epsilon-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (epsilon-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (epsilon-caprolactone) nanofibers and the maintenance of the original structure of poly (epsilon-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (epsilon-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (epsilon-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (epsilon-caprolactone) nanofiber scaffolds.11Ysciescopu

Transcatheter Arterial Embolization as Treatment for a Life-Threatening Retroperitoneal Hemorrhage Complicating Heparin Therapy

Spontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present in the absence of specific underlying pathology or trauma and is typically associated with anticoagulation therapy. We report a case of a 74-year-old female patient with a cerebral infarction related to atrial fibrillation who developed a spontaneous lumbar arterial hemorrhage complicating heparin therapy. The diagnosis was suggested by a computed tomography scan and confirmed by angiography. She was treated successfully with transcatheter embolization