The effect of 2.1 T static magnetic field on astrocyte viability and morphology

The viability and a number of morphological properties of in situ astrocytes of rat spinal cord cultures including changes in surface area and migration of both cell body and nucleus were investigated at magnetic field intensities comparable to those currently used for magnetic resonance imaging. Viability of rat spinal astrocytes was studied after up to 72 hours of 2.1T static magnetic field exposure. Surface areas and two-dimensional centroids of both soma and nucleus after 2 hours of magnetic field exposure were determined and compared with those of the same cells before magnetic field exposure. Cell membrane ruffling was quantified using fractal analysis.     

Biosynthesis and Chemical Characterization of Silver Nanoparticles Using Satureja Rechingeri Jamzad and Their Apoptotic Effects on AGS Gastric Cancer Cells

Journal of Cluster Science - Since green synthesis of silver nanoparticles (AgNPs) is a simple, safe, cost-effective and eco-friendly method, AgNPs appear to be promising anti-cancer agents in the...     

A Turn Off Fluorescence Probe Based on Carbon Dots for Highly Sensitive Detection of BRCA1 Gene in Real Samples and Cellular Imaging

Journal of Fluorescence - In this research, DNA-modified carbon dots (CDs) were exploited to construct a fluorescence assay for breast cancer genes (BRCA1, a potential marker for cancer diagnosis)...     

The identification of toxicophores for the prediction of mutagenicity, hepatotoxicity and cardiotoxicity

The toxic properties of compounds can be related to chemical structures, and more specifically, to particular substructures, called toxicophores. Reliability and accuracy of mutagenicity, hepatotoxicity, or cardiotoxicity predictions may be achieved by identifying toxicophores. These predictions can guide the design of chemical libraries for hit and lead optimization. As such, a thorough molecular knowledge in drug-induced toxicity is required to aid the development of new therapeutic agents and prevent the release of potentially toxic drugs onto the market. The incorporation of these potentially reactive chemical moieties within new therapeutic agents should be limited. This, however, can not always be prevented, particularly when the structural feature responsible for toxicity is also responsible for the pharmacological efficacy. In recent years, there has been strong pressure from society in general, and from government agencies in particular, to develop “general” prediction models in order to cope with the thousands of chemicals present in the environment for which experimental data are not available and likely will never exist. Therefore, one of the objectives of this work is to introduce methodologies capable of identifying the potential environmental health hazards of chemicals. This review also summarizes the evidence for reactive metabolite formation from chemical carcinogens, hepatotoxic drugs, and also describes how and where molecules bind and inhibit hERG K⁺ channels, causing cardiotoxicity by QT prolongation. Such information should dramatically improve our understanding of drug-induced toxic reactions. Indeed, pharmaceutical companies are striving to improve the drug discovery and development process to identify, as early as possible, the risk of novel agents, or their metabolites, causing mutagenicity, hepatocellular toxicity, or QT interval prolongation and to make appropriate go/no-go decisions or modify their development programs accordingly.     

Design, synthesis, and cytotoxicity of 4-sulfonamide substituted benzamidobenzimidazolones and an acyl benzimidazolone

4-Sulfonamide substituted benzamidobenzimidazolones were designed and docked into the active site model of CDK2, using an oxindole inhibitor as the template. Compounds 6a-6i were then prepared from the reaction of the sulfonyl chloride 1 with different amines to give the corresponding acids (2a-2i), which were converted to their corresponding acyl chlorides (3a-3i). Reaction of 3a-3i with o-nitrophenylhydrazine afforded the respective nitro derivatives (4a-4i). The nitro groups were then reduced to give the corresponding amines (5a-5i), which, upon reaction with ethyl chloroformate, the target compounds (6a-6i) were produced. Target benzimidazolone derivatives (9a-9e) were also prepared from the reaction of isopropenyl benzimidazolone (8) with different sulfonyl or acyl chlorides. The target compounds were then tested by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against the cancer cell lines, Hep G2, HT-29, CL1-5 and AGS. Despite similar binding properties of the flexible benzamidobenzimidazolones and rigid cytotoxic oxindole inhibitors at the active site of CDK2, biological screening results indicated that benzamidobenzimidazolones did not exhibit significant cell growth inhibition in vitro. Their analogue, 3-acyl benzimidazolone (12), however, revealed cytotoxicity similar to that of the reference oxindole inhibitor.     

Application of the Barton photochemical reaction in the synthesis of 1-dethia-3-aza-1-carba-2-oxacephem: a novel agent against resistant pathogenic microorganisms

Racemic 7-(phenylacetamido)-1-dethia-3-aza-1-carba-2-oxacephem 3 was synthesized and found to possess antibacterial activity against Staphylococcus aureus FDA 209P, Escherichia coli ATCC 39188, Pseudomonas aeruginosa 1101-75 and Klebsiella pneumoniae NCTC 418 as well as the beta-lactamase producing organisms E. coli A9675 and P. aeruginosa 18S-H and the methicillin-resistant organism S. aureus 95. Formation of the carbacephem 3 originated from the Barton photochemical reaction in the conversion of 8 to 10. Intramolecular cyclization of syn-oximino beta-lactam 10 afforded 7-azido-2-oxa-3-azacephem 11, which was reduced and acylated to 12. Enzymatic removal of the methyl group from 12 gave the target molecule 3.     

Exploring the interaction between “site-markers,aspirin and esterase-like activity” ternary systems on the human serum albumin: direct evidence for modulation of catalytic activity of the protein in different inhibition modes

Albumin which is the most abundant drug carrier protein in plasma controls the distribution aspect of drug pharmacokinetics. The aim of this study has been to elucidate the concurrent binding behavior of indomethacin/ibuprofen/heme to HSA under the effect of aspirin-mediated protein acetylation and also to explore the esterase-like catalytic property of the unmodified/modified proteins, as binary or ternary systems, by using various spectroscopic and molecular docking techniques. We found that aspirin-based modification of HSA affects the protein conformation as well as ligand binding at sites I–III. Decrease in pNPA-mediated esterase activity of HSA in different reversible inhibition modes, upon the protein–ligand interactions, was also documented, an issue that may receive considerable attention for computational prodrug design in near future.     

Are Pro<Superscript>8</Superscript>/Pro<Superscript>18</Superscript> really critical for functional dynamic behavior of human endostatin N-terminal peptide? A comparative molecular dynamics study

Endostatin which is derived from the non-collagenous domain 1 of collagen XVIII and is a recently identified broad spectrum anti-angiogenesis agent, inhibits 65 different tumor types. The N-terminal fragment of endostatin protein (ES) has the same antitumor, antimigration and antipermeability effects as the entire protein. In the current study, we modeled two mutant variants of ES with two mutation sites (M1-ES (Pro⁸ → Ala) and M2-ES (Pro¹⁸ → Ala)) and tried to understand proline’s effect on the peptide structure/stability by introducing P⁸A/P¹⁸A mutations, and then in order to gain functional insight into mutation caused by amino acid substitution to the peptide structure/function, these effects were predicted using computational tools. From the RMSD analyses, it can be concluded that dynamic behavior of wild-type and mutant structures was not significantly different from each other and all systems reached equilibrium. The RMSF analysis also revealed that the M2-ES has smaller overall flexibility than the WT-ES and M1-ES structures. The radius of gyration analysis then confirmed the structure of M2-ES compared to wild-type and M1 variant becomes more compact during simulation of our systems. Finally, molecular dynamics simulation analysis shows that replacement of Pro residue with Ala is able to induce a distinct β-sheet in both mutant structures. Indeed, the docking analysis shows the WT-ES and M2-ES bind to the same region of α_vβ₃ integrin, suggesting similar interaction pattern with a relatively equal binding energy into this receptor. Our results speculated that the P⁸A/P¹⁸A replacements confer no improvement (or no tangible weakness) in the peptide biological activity although is able to change structural conformation of N-terminal fragment of human endostatin protein.