Uncharged isocoumarin-based inhibitors of urokinase-type plasminogen activator

Background  

Urokinase-type plasminogen activator (uPA) plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis. Consequently, uPA is an attractive target for the development of small molecule active site inhibitors. Most of the recent drug development programs aimed at nonpeptidic inhibitors targeted at uPA have focused on arginino mimetics containing amidine or guanidine functional groups attached to aromatic or heterocyclic scaffolds. There is a general problem of limited bioavailability of these charged inhibitors. In the present study, uPA inhibitors were designed on an isocoumarin scaffold containing uncharged substituents.     

Quality control of Citri reticulatae pericarpium: exploratory analysis and discrimination

Extracts of Citri reticulatae pericarpium (PCR) are commonly used in the Traditional Chinese Medicine. The quality control of PCR is currently performed by single marker analysis, which can hardly describe the complexity of such natural samples. In this study, a fingerprint methodology for PCR based on high-performance liquid chromatography (HPLC) was developed and validated. A total of 69 fingerprints of authenticated PCR samples, commercial PCR samples, mixed peel samples, and other Citrus peels were recorded. Exploratory data analysis allowed optimizing the extraction procedure and detecting mixed peel samples. Once the optimizations were performed and the method validated, discrimination between the authentic PCR samples and all other samples was performed by p-Discriminant Partial Least Squares. The established model was able to differentiate between classes with a high reliability for each sample. Furthermore, evaluation of the score and loading plots of the model indicated nobiletin, tangeretin, naringin and hesperidin as important markers for the quality control of PCR.     

Chromatographic separation techniques and data handling methods for herbal fingerprints: a review

As herbal medicines have an important position in health care systems worldwide, their current assessment and quality control are a major bottleneck. Over the past decade, major steps were taken not only to improve the quality of the herbal products but also to develop analytical methods ensuring their quality. Nowadays, chromatographic fingerprinting is the generally accepted technique for the assessment and quality control of herbal products. This paper briefly considers the evolution of the regulations and guidelines on the quality control of herbal medicines, and reviews the established analytical techniques for herbal fingerprinting with an emphasis on the most recent developments, such as miniaturized techniques, new stationary phases, analysis at high temperatures and multi-dimensional chromatography. Accessory to the new analytical techniques, the chemometric data handling techniques applied are discussed. Chemometrics provide scientists with useful tools in understanding the huge amounts of data generated by the analytical advances and prove to be valuable for quality control, classification and modelling of, and discrimination between herbal fingerprints.     

Calix[4]arenes as Molecular Platforms for Magnetic Resonance Imaging (MRI) Contrast Agents

The novel amphipilic conjugate of a calix[4]arene with four Gd–1,4,7,10‐ tetra(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (DOTA) chelates has potential as a magnetic resonance imaging contrast agent, both in its monomeric and in its micellar form. The system, illustrated here with its nuclear magnetic relaxation profile, shows good relaxivities, thanks to its high rigidity.

     

Normal co-ordinate analyses and structural considerations of TeCl4, TeBr4 and TeCl2Br2

The molecular structure of TeCl₂Br₂ in the vapour phase is reconsidered in the light of the recently published X-ray crystal structure for TeCl₄. Normal coordinate calculations are performed on molecular TeCl₂Br₂ in its three possible symmetries using force fields derived from the parent molecules TeCl₄ and TeBr₄. The calculations indicate that the data for molecular TeCl₂Br₂ can best be interpreted as arising from a mixture of at least the two high symmetry conformers rather than just the low symmetry C₁ molecule as previously reported.     

Integrated band intensities in N2O4 in the infrared range

We have measured the integrated band intensities of the ν₉ and ν₁₁ bands of N₂O₄ which are observed around 1757 and 1261 cm^-1, respectively. By varying temperature and pressure, we have obtained: S_band(ν₉) = 9.60(130), 9.10(24), 8.80(66) and S_band(ν₁₁)= 5.93(64), 5.70(21) and 5.33(46) (in 10^-17 cm/molecule) at 293.15 (60), 277.25 (60) and 261.65 (60) K, respectively.     

Theory for the nonlinear optical response at noble-metal surfaces with nonequilibrium electrons

We present a theory for the electron-temperature dependence T _el of optical second harmonic generation (SHG). Such an analysis is required to study the dynamics of metallic systems with many hot electrons not at equilibrium with the lattice. Using a tight-binding theory for the nonlinear susceptibility χ ⁽²⁾(ω,T _e1) and the Fresnel coefficients we present results for the SHG intensity I ⁽²⁾(ω,T _e1) and its dependence on T _el for Cu. Note, χ ⁽²⁾(ω,T _e1) rather than the Fresnel coefficients determines essentially this temperature dependence. Most interestingly we find frequency ranges where I ⁽²⁾(ω,T _e1) increases for small light intensities, while it decreases for large light intensities. Our theory yields also that SHG probes effects due to hot electrons more sensitively than linear optics. The results of our calculations are compared with recent experiments on Cu and Au.