Design,Synthesis, and Biological Evaluation of Quercetagetin Analogues as JNK1 Inhibitors

The recent discovery of c‐Jun NH₂‐terminal kinase JNK1 suppression by natural quercetagetin ( 1 ) is a promising lead for the development of novel anticancer agents. Using both X‐ray structure and docking analyses we predicted that 5′‐hydroxy‐ ( 2 ) and 5′‐hydroxymethyl‐quercetagetin ( 3 ) would inhibit JNK1 more actively than the parent compound 1 . Notably, our drug design was based on the active enzyme–ligand complex as opposed to the enzyme’s relatively open apo structure. In this paper we test our theoretical predictions, aided by docking‐model experiments, and report the first synthesis and biological evaluation of quercetagetin analogues 2 and 3 . As calculated, both compounds strongly suppress JNK1 activity. The IC₅₀ values were determined to be 3.4 μM and 12.2 μM , respectively, which shows that 2 surpasses the potency of the parent compound 1 (IC₅₀=4.6 μM ). Compound 2 was also shown to suppress matrix metalloproteinase‐1 expression with high specificity after UV irradiation.     

The conformational locking of asparagine

One dominant structure has been identified analysing the rotational spectrum of asparagine in sharp contrast with the multiconformational behaviour for other amino acids with polar side chains. This locking of the conformational variety to a single conformer has been ascribed to an intramolecular hydrogen bonding network involving α-amine, α-carboxylic and amide groups.     

Multilayered artifacts in the pre-Columbian metallurgy from the North of Peru

Three types of alloys were recognized when analyzing pre-Columbian artifacts from the North of Peru: gold, silver, and copper alloys; gilded copper and silver; silvered copper; tumbaga, i.e., copper or silver enriched on gold at the surface by depletion gilding. In this paper, a method is described to differentiate gold alloys from gilded copper and from copper–gold tumbaga, and silver alloys from silvered copper and copper–silver tumbaga. This method is based on the use of energy-dispersive X-ray fluorescence, i.e., on a sophisticated analysis of XRF-spectra carrying out an accurate determination of Cu(K _α /K _β ), Ag(K _α /K _β ), Au(L _α /L _β ), and Au-L _α /Cu-K _α or Ag-K _α /Cu-K _α ratios. That implies a dedicated software for the quantitative determination of the area of X-ray peaks. This method was first checked by a relevant number of standard samples and then it was applied to pre-Columbian alloys from the North of Peru.     

Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella alata (Anura: Bufonidae): Antiprotozoal Activity against Trypanosoma cruzi

Toads in the family Bufonidae contain bufadienolides in their venom, which are characterized by their chemical diversity and high pharmacological potential. American trypanosomiasis is a neglected disease that affects an estimated 8 million people in tropical and subtropical countries. In this research, we investigated the chemical composition and antitrypanosomal activity of toad venom from Rhinella alata collected in Panama. Structural determination using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy led to the identification of 10 bufadienolides. Compounds identified include the following: 16β-hydroxy-desacetyl-bufotalin-3-adipoyl-arginine ester (1), bufotalin (2), 16β-hydroxy-desacetyl-bufotalin-3-pimeloyl-arginine ester (3), bufotalin-3-pimeloyl-arginine ester (4), 16β-hydroxy-desacetyl-bufotalin-3-suberoyl-arginine ester (5), bufotalin-3-suberoyl-arginine ester (6), cinobufagin-3-adipoyl-arginine ester (7), cinobufagin-3-pimeloyl-arginine ester (8), cinobufagin-3-suberoyl-arginine ester (9), and cinobufagin (10). Among these, three new natural products, 1, 3, and 5, are described, and compounds 1–10 are reported for the first time in R. alata. The antitrypanosomal activity assessed in this study revealed that the presence of an arginyl-diacid attached to C-3, and a hydroxyl group at C-14 in the structure of bufadienolides that is important for their biological activity. Bufadienolides showed cytotoxic activity against epithelial kidney Vero cells; however, bufagins (2 and 10) displayed low mammalian cytotoxicity. Compounds 2 and 10 showed activity against the cancer cell lines MCF-7, NCI-H460, and SF-268.     

Simultaneous measurement with one-capture of the two in-plane components of displacement by electronic speckle pattern interferometry

We present the simultaneous measurement of the two in-plane displacement components by electronic speckle pattern interferometry with three object beams and without an in-line reference beam. Three interference fringe patterns, corresponding to three different sensitivity vectors, are recorded in a single interferogram and separated by means of the Fourier transform method. Then, two interference fringe patterns are selected to obtain the in-plane displacement components.     

Ion-Tagged Oligonucleotides Coupled with a Magnetic Liquid Support for the Sequence-Specific Capture of DNA

The isolation of specific nucleic acid sequences is a major bottleneck in molecular diagnostics. Magnetic beads/particles are typically used as solid supports for the capture of DNA targets to improve sample throughput but aggregate over time resulting in lower capture efficiency and obstruction of liquid handling devices. Herein, we describe a particle-free approach to sequence-specific DNA extraction using a magnetic liquid support and ion-tagged oligonucleotide (ITO) probes. ITO conjugates were synthesized with the highest yields ever achieved for the radical thiol-ene coupling of a substrate and oligonucleotide. In addition to distinguishing nucleotide mismatches, the ITO and magnetic liquid-based approach was more sensitive than a commercial magnetic bead-based method for the capture of target DNA from a pool of interfering genomic DNA.     

Syntheses and X-ray characterization of metal complexes with the pentadentate thiosemicarbazone ligand bis(4-N-methylthiosemicarbazone)-2,6-diacetylpyridine. The first pentacoordinate lead(II) complex with a pentagonal geometry

In this paper we describe the electrochemical synthesis and characterization of new neutral manganese, iron, cobalt, nickel, copper, zinc, cadmium and lead complexes with the ligand bis(4-N-methylthiosemicarbazone)-2,6-diacetylpyridine, H4DAPTsz-Me. X-Ray structures of [Mn(H2DAPTsz-Me)(EtOH)2] 1, [Pb(H2DAPTsz-Me)] 3 and [Zn(H2DAPTsz-Me)]2.EtOH.2H2O 4, were also determined. In these complexes the ligand behaves as bis-deprotonated and SNNNS pentadentate. In the manganese complex the metal is heptacoordinated, in a distorted pentagonal-bipyramidal environment, with the N3S2 donor set of the ligand in the pentagonal girdle and two solvent molecules occupying the axial positions. In the lead complex 3 the metal is pentacoordinated, bound exclusively to the five donor atoms of the ligand, as a consequence of the existence of "inert pair effect". The bishelical zinc complex 4 shows each zinc atom with different coordination geometry, one octahedrally six-coordinate while the other is distorted tetrahedrally four-coordinate.     

Surfaces Coated with Polymer Brushes Work as Carriers for Histidine Ammonia Lyase

The immobilization of enzymes on solid supports is an important challenge in biotechnology and biomedicine. In contrast to other methods, enzyme deposition in polymer brushes offers the benefit of high protein loading that preserves enzymatic activity in part due to the hydrated 3D environment that is available within the brush structure. The authors equipped planar and colloidal silica surfaces with poly(2-(diethylamino)ethyl methacrylate)-based brushes to immobilize Thermoplasma acidophilum histidine ammonia lyase, and analyzed the amount and activity of the immobilized enzyme. The poly(2-(diethylamino)ethyl methacrylate) brushes are attached to the solid silica supports either via a “grafting-to” or a “grafting-from” method. It is found that the grafting-from method results in higher amounts of deposited polymer and, consequently, higher amounts of Thermoplasma acidophilum histidine ammonia lyase. All polymer brush-modified surfaces show preserved catalytic activity of the deposited Thermoplasma acidophilum histidine ammonia lyase. However, immobilizing the enzyme in polymer brushes using the grafting-from method resulted in twice the enzymatic activity from the grafting-to approach, illustrating a successful enzyme deposition on a solid support.     

Electrochemical synthesis of manganese(II)-Schiff base complexes and their behaviour towards H2O,H2O2 and SO2

Manganese(II) complexes with ONNO tetradentate Schiff bases have been prepared by electrochemical synthesis and characterised by analytical and spectroscopic techniques, magnetism and by studying their redox reversibility character by cyclic and normal pulse voltammetry. The ability of these systems to catalyse the decomposition of water, to yield dioxygen, and their catalase-like activity was checked. Reaction of the complexes with sulfur dioxide was studied in the solid state and in toluene slurries at room temperature. The adducts formed underwent thermogravimetric desorption analyses that highlights the SO₂-irreversible linkage present in all complexes.     

Different field distributions obtained with an axicon and an amplitude mask

A combination of an axicon and an amplitude mask is used to obtain an intensity distribution that differs from the typical Bessel one. Experimental and numerical characterization of the field is made for different propagation distances and types of amplitude masks.