Design,Synthesis and Anticancer Activity of a New Series of N-aryl-N′-[4-(pyridin-2-ylmethoxy)benzyl]urea Derivatives

The development of cancer treatments requires continuous exploration and improvement, in which the discovery of new drugs for the treatment of cancer is still an important pathway. In this study, based on the molecular hybridization strategy, a new structural framework with an N-aryl-N’-arylmethylurea scaffold was designed, and 16 new target compounds were synthesized and evaluated for their antiproliferative activities against four different cancer cell lines A549, MCF7, HCT116, PC3, and human liver normal cell line HL7702. The results have shown seven compounds with 1-methylpiperidin-4-yl groups having excellent activities against all four cancer cell lines, and they exhibited scarcely any activities against HL7702. Among them, compound 9b and 9d showed greatly excellent activity against the four kinds of cells, and the IC₅₀ for MCF7 and PC3 cell lines were even less than 3 μM.     

Synthesis and evaluation of N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogous as anticancer,anti-angiogenic & antioxidant agents: In vitro and in silico analysis

N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogues (flutamides) are versatile scaffolds with a wide spectrum of biological activities. A series of new N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides (8a-t) and their N-ethyl analogous (9a-t) were synthesized and characterized. The inhibitory potential of the synthesized compounds on the viability of three human cancer cell lines HEP3BPN 11 (liver), MDA-MB 453 (breast), and HL 60 (leukemia) were assessed. Among all the compounds 8 L, 8q, 9n and 9p showed higher inhibitory activity on the viability of HL 60 than the standard methotrexate. These lead molecules were then tested for their potential to inhibit the activity of proangiogenic cytokines. The compound 9n showed significantly better inhibition against two cytokines viz. TNFα and Leptin as compared to the standard suramin, while 9p has activity comparable to suramin against IGF1, VEGF, FGFb, and Leptin. The 8q is found to be strong antiangiogenic agent against IGF1, VEGF and TGFβ; while 8 L has showed activity against TNFα, VEGF, and Leptin inhibition. Furthermore antioxidant potential of 8a–t and 9a-t compounds was screened using DPPH, OH and SOR radical scavenging activities. The OH radical scavenging activity of 8c and DPPH activities of 9n as well as 9o are significant as compared to respective standards ascorbic acid and α-tocopherol. The 8c, 9p and 9 h have also exhibited potential antioxidant activity. Additionally, we present in silico molecular docking data to provide the structural rationale of observed TNFα inhibition against newly synthesized compounds. Overall, the synthesized flutamide derivatives have not only anticancer activity, but also possess dual inhibitory effect (anti-angiogenesis and antioxidant) and hence can act as a promising avenue to develop further anticancer agents.     

Advanced Nanomaterials for Multimodal Molecular Imaging

The development of multimodal molecular imaging contrast agents based on versatile nanomaterials has recently attracted much attention in disease diagnosis and therapeutic delivery. Contrast agents made from nanoparticles and used for multimodal imaging in vivo provide a multidimensional pathophysiological overview of diseases. This review summarizes recently developed advanced nanomaterials for multimodal molecular imaging. We comprehensively discuss these nanoparticle contrast agents in terms of their targeting modalities, limitations in clinical translation and future directions.     

Spatial and temporal resolution effects on dynamic contrast-enhanced magnetic resonance mammography

We tested the hypothesis that partial volume effects due to poor in-plane resolution and/or low temporal resolution used in clinical dynamic contrast-enhanced magnetic resonance imaging results in erroneous diagnostic information based on inaccurate estimates of tumor contrast agent extravasation and tested whether reduced encoding techniques can correct for dynamic data volume averaging. Image spatial resolution was reduced from 469 x 469 microm2 to those reported below by selecting a subset of k-space data. We then compared the top five K(trans)/V(T) "hot spots" obtained from the original data set, 469 x 469-microm in-plane spatial resolution and an 18-s temporal resolution processed by fast Fourier transform (FFT), with values obtained from data sets having in-plane spatial resolutions of 938 x 938, 1875 x 1875 and 2500 x 2500 microm2 and a temporal resolution of 18 s, or data sets with temporal resolutions of 36, 54 and 72 and a spatial resolution of 469 x 469 microm2, and found them to statistically differ from the parent data sets. We then tested four different post processing methods for improving the spatial resolution without sacrificing temporal resolution: zero-filled FFT, keyhole, reduced-encoding imaging by generalized-series reconstruction (RIGR) and two-reference RIGR (TRIGR). The top five values of K(trans)/V(T) obtained from data sets, the in-plane spatial resolutions of which were improved to 469 x 469 microm2 by zero-filling FFT, Keyhole and RIGR, statistically differed from those obtained from the original 469 x 469 microm2 FFT parent image data set. Only the 938 x 938 and 1875 x 1875 microm2 data sets reconstructed to 469 x 469 microm2 with TRIGR reconstruction method yielded values of the top five K(trans)/V(T) hot spots statistically the same as the original parent data set, 469 x 469 microm2 in-plane spatial and 18-s temporal-resolution FFT. That is, partial volume effects from data sets of different in-plane spatial resolution resulted in statistically different values of the top five K(trans)/V(T) hot spots relative to a high spatial and temporal resolution data set, and TRIGR reconstruction of these low resolution data sets to high resolution images provided statistically similar values with a savings in temporal resolution of 2 to 4 times.     

Pixel-by-pixel analysis of DCE MRI curve patterns and an illustration of its application to the imaging of the musculoskeletal system

Dynamic contrast enhanced (DCE) MRI is a widespread method that has found broad application in the imaging of the musculoskeletal (MSK) system. A common way of analyzing DCE MRI images is to look at the shape of the time-intensity curve (TIC) in pixels selected after drawing an ROI in a highly enhanced area. Although often applied to a number of MSK affections, shape analysis has so far not led to a unanimous correlation between these TIC patterns and pathology. We hypothesize that this might be a result of the subjective ROI approach. To overcome the shortcomings of the ROI approach (sampling error and interuser variability, among others), we created a method for a fast and simple classification of DCE MRI where time-curve enhancement shapes are classified pixel by pixel according to their shape. The result of the analysis is rendered in multislice, 2D color-coded images. With this approach, we show not only that differences on a short distance range of the TIC patterns are significant and cannot be appreciated with a conventional ROI analysis but also that the information that shape maps and conventional standard DCE MRI parameter maps convey are substantially different.     

Germaborenes: Borylene Transfer Agents for the Synthesis of Iminoboranes

Halide and phenyl substituted germaborenes were shown to react with azides at room temperature and transfer a borylene moiety to give iminoboranes. This iminoborane synthesis based on a borylene transfer route was investigated computationally in the case of the phenyl substituted germaborene.     

Preparation of hybrid microcapsules and application to self‐healing agent

It was tried to prepare hybrid microcapsules composed of porous inorganic particles and epoxy resin shell and to apply to the self‐healing agent. A water soluble imidazole of gelation promoting agent as the core material was microencapsulated in the porous inorganic particles, which were coated with epoxy resin. The porous inorganic particles were prepared with the interfacial reaction between sodium silicate and calcium ion in the (W/O) dispersion. In the experiment, the concentration of sodium silicate and the mixing speed to form the (W/O) dispersion were mainly changed. The porous inorganic particles were immersed in the aqueous solution dissolving imidazole and then, added in the corn oil dissolving epoxy resin to be microencapsulated with gelated epoxy resin. The hybrid microcapsules containing imidazole with the mean diameters from 200 to 400 µm were able to be prepared and to induce the gelation reaction of epoxy resin by breaking the hybrid microcapsule shell due to heating. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of conditional stability constants for some divalent transition metal ion‐EDTA complexes by electrospray ionization mass spectrometry

Conditional stability constants of coordination complexes comprising divalent transition metals, Cu²⁺, Ni²⁺, Zn²⁺, Co²⁺, and ethylenediaminetetraacetic acid (EDTA) were determined utilizing electrospray ionization mass spectrometry. The deviation of signal response of a reference complex was monitored at addition of a second metal ion. The conditional stability constant for the competing metal was then determined through solution equilibria equations. The method showed to be applicable to a system where Co²⁺ and Zn²⁺ competed for EDTA at pH 5. When Cu²⁺ and Ni²⁺ competed for EDTA, the equilibrium changed over time. This change was shown to be affected in rate and size by the type of organic solvent added. In this work, 30% of either methanol or acetonitrile was used. It was found that if calibration curves are prepared for both metal complexes in solution and the measurements are repeated with sufficient time space, any change in equilibrium of sample solutions will be discovered. Copyright © 2014 John Wiley & Sons, Ltd.     

Alkyl Ammonium Cation Stabilized Biocidal Polyiodides with Adaptable High Density and Low Pressure

The effective application of biocidal species requires building the active moiety into a molecular back bone that can be delivered and decomposed on demand under conditions of low pressure and prolonged high‐temperature detonation. The goal is to destroy storage facilities and their contents while utilizing the biocidal products arising from the released energy to destroy any remaining harmful airborne agents. Decomposition of carefully selected iodine‐rich compounds can produce large amounts of the very active biocides, hydroiodic acid (HI) and iodine (I₂). Polyiodide anions, namely, I₃^?, I₅^?, which are excellent sources of such biocides, can be stabilized through interactions with large, symmetric cations, such as alkyl ammonium salts. We have designed and synthesized suitable compounds of adaptable high density up to 3.33 g cm^?3 that are low‐pressure polyiodides with various alkyl ammonium cations, deliverable iodine contents of which range between 58.0–90.9 %.     

Efficient Biocatalytic Degradation of Pollutants by Enzyme‐Releasing Self‐Propelled Motors

The first example of a self‐propelled tubular motor that releases an enzyme for the efficient biocatalytic degradation of chemical pollutants is demonstrated. How the motors are self‐propelled by the Marangoni effect, involving simultaneous release of SDS surfactant and the enzyme remediation agent (laccase) in the polluted sample, is illustrated. The movement induces fluid convection and leads to the rapid dispersion of laccase into the contaminated solution and to a dramatically accelerated biocatalytic decontamination process. The greatly improved degradation efficiency, compared to quiescent solutions containing excess levels of the free enzyme, is illustrated for the efficient biocatalytic degradation of phenolic and azo‐type pollutants. The high efficiency of the motor‐based decontamination approach makes it extremely attractive for a wide‐range of remediation processes in the environmental, defense and public health fields.