Design,Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents

Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.     

Live cell labeling of native intracellular bacterial receptors using aniline-catalyzed oxime ligation

Live cell fluorescent labeling of proteins has become a seminal tool in biology and has led to hallmark discoveries in diverse research areas such as protein trafficking, cell-to-cell interactions, and intracellular network dynamics. One of the main challenges, however, remains the ability to label intracellular proteins using fluorescent ligands with high specificity, all the while retaining viability of the targeted cells. Here, we present the first example of live cell labeling and imaging of an intracellular bacterial receptor involved in cell-to-cell communication (i.e., quorum sensing), using a novel two-step approach involving covalent attachment of a reactive mimic of the primary endogenous Pseudomonas aeruginosa quorum-sensing signal to its receptor, LasR, followed by aniline-catalyzed oxime formation between the modified receptor and a fluorescent BODIPY derivative. Our results indicate that LasR is not distributed evenly throughout the cytoplasmic membrane but is instead concentrated at the poles of the P. aeruginosa cell.     

Characterization and catalytic activity of unsupported FeV and K-FeV catalysts for diesel soot combustion

A microstructural characterization by XRD, FT-IR and temperature programmed reduction (TPR) of unsupported FeV and K-FeV catalysts, prepared by solid-state synthesis, is reported. The formation of FexVyOz mixed phases of different compositions has been evidenced depending on the V/Fe ratio and calcination temperature. The catalytic activity of the samples in the combustion of diesel soot has been investigated with the aim to understand the role of FexVyOz mixed phases in the title reaction. This revised version was published online in August 2006 with corrections to the Cover Date.     

Hexagonal mesoporous silica modified with copper phthalocyanine as a photocatalyst for pesticide 2,4-dichlorophenoxiacetic acid degradation

A new mesoporous catalyst was prepared by the reaction between 3-aminopropyltrimethoxisylane and Cu(II)-hexadecafluorophthalocyanine, followed by co-condensation of tetraethylorthosilicate around a micelle formed by n-dodecylamine. The surfactant was removed from the pores by continuous extraction with ethanol, giving the Si-CuF16Pc catalyst. This catalyst was characterized by SEM, FTIR, TGA, 29Si NMR, N2 adsorption and X-ray diffraction. SEM images confirmed that the catalyst material is formed by nanoaggregates with a diameter of 100 nm. N2 adsorption isotherms showed that Si-CuF16Pc has a surface area of approximately 200 m2 g(-1) and a porous diameter of 7.7 nm, characterizing the mesoporosity of this product. This novel material shows an excellent photocatalytic activity, degrading almost 90% of 2,4-dichlorophenoxyacetic acid (2,4-D) up to 30 min, while only approximately 40% of photodegradation was obtained in its absence.     

Magnetic resonance imaging of bone marrow metastasis with fluid-fluid levels from small cell neuroendocrine carcinoma of the urinary bladder

Fluid-fluid levels have been reported as an extremely infrequent and non-specific condition in many benign and malignant bone lesions. We present the first reported MRI findings of bone marrow metastasis with fluid-fluid levels from small cell neuroendocrine carcinoma of the urinary bladder to the lumbar spine. Radiologists should be aware of the MRI appearance of these extraordinary lesions in order to provide a complete differential diagnosis and to guide clinicians in adequate treatment.     

A comparison between nonlinear cantilever and buckled beam for energy harvesting

Nonlinear dynamics has become one of the key aspect to improve the efficiency of kinetic energy harvesters working in the real environment. Different methods based on the exploitation of the dynamical features of stochastic nonlinear oscillators using bi-stable piezoelectric cantilevers or buckled beams have been proposed in the past years. Such methods are shown to outperform standard linear oscillators and to overcome some of the most severe limitations of present approaches once applied to ambient vibrations. This work presents simulation results comparing the two methods. The same piezoelectric element subjected to a fixed vibrating body in a cantilever or bridge configuration has been simulated. The kinetic excitation considered is a zero mean exponentially correlated gaussian noise with different amplitudes. The piezoelectric oscillator output response has been obtained as a function of a nonlinear parameter. This work is intended to help designing the most performing energy harvester for real world applications starting from the same piezoelectric element.     

Sequence stereoisomerism in calixarene-based pseudo[3]rotaxanes

Two calix[6]arene directional wheels can be ordered in the right stereosequence by their through-the-annulus threading with a rationally designed bis(benzylalkylammonium) axle. These stereoisomeric pseudo[3]rotaxanes can be considered as a minimal "informational system" because the "written information" on the thread is transferred to a specific sequence stereoisomer.