Design,Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines

The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC₅₀ values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.     

An open source protein gel documentation system for proteome analyses

Data organization and data mining represents one of the main challenges for modern high throughput technologies in pharmaceutical chemistry and medical chemistry. The presented open source documentation and analysis system provides an integrated solution (tutorial, setup protocol, sources, executables) aimed at substituting the traditionally used lab-book. The data management solution provided incorporates detailed information about the processing of the gels and the experimental conditions used and includes basic data analysis facilities which can be easily extended. The sample database and User-Interface are available free of charge under the GNU license from http://webber.physik.uni-freiburg.de/~fallerd/tutorial.htm.     

Synthesis of novel isoxazole-linked steroidal glycoconjugates—an application of a novel steroidal nitrile oxide

Isoxazole-linked steroidal glycoconjugates are prepared by 1,3-dipolar cycloaddition reactions of an in situ generated and hitherto unknown steroidal nitrile oxide with appropriate propargyl ethers of sugars. The methodology provides a novel vector in the form of an easily accessible nitrile oxide having the ability to couple with many biomolecules, thus offering a new pathway to construct biologically significant novel steroidal conjugates.     

Role of ligands in the formation, phase stabilization, structural and magnetic properties of α-Fe2O3 nanoparticles

The electrochemical synthesis of alpha Fe₂O₃ nanoparticles was performed using quaternary ammonium salts viz. TPAB, TBAB and TOAB in an organic medium by optimizing current density and molar concentration of the ligand. The role of ligands in the formation of α phase, structure and magnetic properties was investigated in details. The effect of increasing chain length on the particle size confirmed that as the chain length increases from propyl to octyl, the particle size decreases. X-ray diffraction spectra of as prepared samples and TEM analysis confirmed the amorphous nature of iron oxide. TEM showed beads of iron oxide joined together with a size distribution in the range of 6–30 nm. The Mossbauer studies also support this observation that for the lowest particle size, the line width is broader which successively reduces with increase in particle size. Iron oxide capped with TOAB indicated superparamagnetic nature at room temperature. The resultant internal magnetic field of 506 mm/s due to hyperfine splitting clearly established the formation of α-Fe₂O₃ The infrared spectroscopy and pH measurements revealed the binding of tetra alkyl ligand with iron oxide. The IR spectra and the increase in basicity of as prepared samples confirmed the formation of hydrated iron oxide. Above 800°C the spectra indicated only iron oxide. Surface area obtained by BET method was 205 m²/g.     

Development and Validation of a Stability-Indicating LC Method for Curcumin

A simple, isocratic, stability-indicating liquid chromatographic method for quantitative determination of curcumin was successfully developed. The chromatographic separations were achieved using a Hi-Q-Sil C18; 4.6 mm × 250 mm and 10 μm particle size column employing acetonitrile and acetate buffer (pH 3.0; 60: 40, v/v) as the mobile phase. The analyte was subjected to acidic, basic, oxidative, thermal and photo degradation. The method was validated with respect to linearity, precision, accuracy, limit of detection and limit of quantification. Curcumin was detected by UV-Vis detector at 425 nm whereas the degradation products were detected at 280 nm. The method was linear over the concentration range of 1–10 μg mL^?1. The limit of detection was found to be 0.06 μg mL^?1 and the quantification limit was 0.21 μg mL^?1. Considerable degradation of the analyte was observed when it was subjected to alkaline conditions. Accuracy, evaluated as recovery, was in the range of 97–103%. Intra-day precision and intermediate precision showed relative standard deviations <1% and <2% respectively.     

Shock response of a heavy tungsten alloy

This article describes the results of shock wave experiments performed on a heavy tungsten alloy containing W, Ni, and Fe in the ratio of 92.85:4.9:2.25 by weight. These experiments provide information about the shear strength under compression and tensile strength, as measured by the spall threshold, of this alloy to 24 GPa. The results of these experiments show that: (i) the magnitude of its Hugoniot elastic limit (HEL) is 2.76±0.26 GPa; (ii) this alloy deforms plastically above its HEL and thus retains its shear strength to 24 GPa; (iii) the spall strength of the alloy is found to be 1.9±0.4 GPa and is independent of the impact stress and duration of the shock compression pulse; and (iv) the tensile impedance of the alloy, determined from a new experiment designed to measure this impedance, is 68±10 Gg/m² s.     

One-Pot Multicomponent Synthesis,Molecular Docking,and In Vitro Antibacterial Activities of 1-{(Aryl)[(5-methyl-1,3-thiazol-2-yl)amino]methyl}naphthalen-2-ol

Russian Journal of Organic Chemistry - A series of new Betti bases, 1-{(aryl)[(5-methyl-1,3-thiazol-2-yl)amino]methyl}naphthalen-2-ols, have been synthesized via one-pot three-component reaction of...     

A miniature cytometry platform for capture and characterization of T-lymphocytes from human blood

Given the clinical and diagnostic importance of blood analysis, there is considerable interest in developing novel miniature devices for rapid characterization of blood constituents. The present paper describes development of a miniature cytometry platform aimed at analysis of T-lymphocytes from peripheral human blood. Microarrays of T-cell-specific antibodies (Abs), including anti-CD3, -CD4, -CD8 and mouse IgG (negative control) were robotically printed onto glass slides coated with a non-fouling poly(ethylene glycol) (PEG) hydrogel. The glass substrates containing Ab arrays were incubated with 100 μL of red blood cell (RBC)-depleted whole human blood for 15 min and then exposed to a controlled shear of ∼2 dyn cm⁻² for additional 10 min. This process led to the removal of non-specific leukocytes and “development” of patterns of T-cells captured on the Ab spots. The immunofluorescent staining of the surface-bound cells revealed the presence of purified CD4⁺ and CD8⁺ T-cells (purity >94%) on their respective Ab spots. Importantly, the proportions of CD4⁺ and CD8⁺ T-cells captured on the Ab spots correlated closely (R² − 0.9) with flow cytometry analysis of T-cell subsets in blood. Overall, this cytometry platform allowed to rapidly (under 30 min) capture pure T-cell subsets from minimally processed human blood. Significantly, our device provided quantitative information about subset abundance solely based on the location of cells within the microarray. This cytometry platform is envisioned as a miniature immunology tool for determination of T-cell phenotype and will have immediate applications in HIV diagnostics and research.     

Design,Synthesis and Evaluation of Substituted N-(3-Arylpropyl)-9,10-dihydro-9-oxoacridine-4-carboxamides as Potent MDR Reversal Agents in Cancer

A novel class of molecules with structure N‐(3‐arylpropyl)‐9,10‐dihydro‐9‐oxoacridine‐4‐carboxamides ( 20 – 29 ) were designed by generating a pharmacophore for potent MDR reversal activity using phase drug design software. The designed molecules were synthesized by a novel synthesis route and evaluated for their inhibitory effects on the transport activity of P‐glycoprotein (P‐gp) by standard Hoechst 33342 assay method. Based on the pIC₅₀ values of ten title compounds screened, three compounds exhibited better activity as compared to Verapamil used as standard.     

A hydrophobic starch polymer for nanoparticle-mediated delivery of docetaxel

A hydrophobic starch derivative is used for safe and enhanced delivery of anticancer agents. The synthesis and characterization of propyl starch with a controlled degree of substitution to modulate the release of the encapsulated hydrophobic drug is reported. The application of this polymer for formulating nanoparticles of docetaxel, an anti-cancer agent effective against numerous types of cancers but possessing intrinsic formulation difficulties is described. The solvent emulsification/diffusion technique is used and the synthesis is optimized with respect to several formulation parameters. Uptake studies with these nanoparticles indicate their enhanced internalization by the cancerous cells and their peri-nuclear localization.