Quinic acids from Aster caucasicus and from transgenic callus expressing a beta-amyrin synthase

Several different classes of secondary metabolites, including flavonoids, triterpenoid saponins and quinic acid derivatives, are found in Aster spp. (Fam. Asteraceae). Several Aster compounds revealed biological as well as pharmacological activities. In this work, a phytochemical investigation of A. caucasicus evidenced the presence of quinic acid derivatives, as well as the absence of triterpene saponins. To combine in one species the production of different phytochemicals, including triterpenes, an Agrobacterium-mediated transformation of A. caucasicus was set up to introduce A. sedifolius beta-amyrin synthase (AsOXA1)-encoding gene under the control of the constitutive promoter CaMV35S. The quali-quantitative analysis of transgenic calli with ectopic expression of AsOXA1 showed, in one sample, a negligible amount of triterpene saponins combined with higher amount of quinic acid derivatives as compared with the wild type callus.     

Phenotypic and Target-Directed Screening Yields New Acaricidal Alternatives for the Control of Ticks

Rhipicephalus microplus, the “common cattle tick”, is the most important ectoparasite in livestock worldwide due to the economic and health losses it produces. This tick is a vector for pathogens of several tick-borne diseases. In Latin American countries, damages reach approximately USD 500 million annually due to tick infections, as well as tick-borne diseases. Currently, resistant populations for every chemical group of acaricides have been reported, posing a serious problem for tick control. This study aims to find new alternatives for controlling resistant ticks with compounds derived from small synthetic organic molecules and natural origins. Using BME26 embryonic cells, we performed phenotypic screening of 44 natural extracts from 10 Mexican plants used in traditional medicine, and 33 compounds selected from our chemical collection. We found 10 extracts and 13 compounds that inhibited cell growth by 50% at 50 µg/mL and 100 µM, respectively; the dose-response profile of two of them was characterized, and these compounds were assayed in vitro against different life stages of Rhipicephalus microplus. We also performed a target-directed screening of the activity of triosephosphate isomerase, using 86 compounds selected from our chemical collection. In this collection, we found the most potent and selective inhibitor of tick triosephosphate isomerase reported until now. Two other compounds had a potent acaricidal effect in vitro using adults and larvae when compared with other acaricides such as ivermectin and Amitraz. Those compounds were also selective to the ticks compared with the cytotoxicity in mammalian cells like macrophages or bovine spermatozoids. They also had a good toxicological profile, resulting in promising acaricidal compounds for tick control in cattle raising.     

Click and count: specific detection of acid ceramidase activity in live cells

The use of intact cells in medical research offers a number of advantages over employing cell-free systems. In diagnostics, cells isolated from liquid biopsies can be directly used, speeding up the time of analysis and diminishing the risk of protein degradation by sample manipulation. In drug discovery, studies in live cells take into account aspects neglected in cell-free systems, such as uptake, metabolization, and subcellular concentration by compartmentalization of potential drug candidates. Therefore, probes for studies in cellulo are of paramount importance. Acid ceramidase (AC) is a lysosomal enzyme that hydrolyses ceramides into sphingoid bases and fatty acids. The essential role of this enzyme in the outburst and progress of several diseases, some of them still incurable, is well sustained. Despite the great clinical relevance of AC as a biomarker and therapeutic target, the specific monitoring of AC activity in live cells has remained elusive due to the concomitant existence of neutral and alkaline ceramidases. In this work, we report that 1-deoxydihydroceramides are exclusively hydrolysed by AC. Using N-octanoyl-18-azidodeoxysphinganine as a probe and a BODIPY-substituted bicyclononyne, we show the click-reliant predominant staining of lysosomes, with extra-lysosomal labeling also occurring in some cells. Importantly, using pharmacological and genetic tools together with high resolution mass spectrometry, we demonstrate that both lysosomal and extra-lysosomal staining are AC-dependent. These findings are translated into the specific flow cytometry monitoring of AC activity in intact cells, which fills an important gap in the field of diseases linked to altered AC activity.

The use of intact cells in medical research offers a number of advantages over employing cell-free systems.     

A novel synthesis of 3-cyanoindoles and a new route to indole-3-carboxylic acid derivatives

2-Alkyl-3-cyanoindoles are obtained when 1-alkylmethyl-2-chloro-(or 2-phenylsulfonyl)-3-phenylsulfonylindoles are reacted with excess azide ion (90°/DMF). The reaction is considered to occur by a fragmentation recombination process in which the Schiff's base $\text{12}$ is of central importance. This proposal is supported by the formation of 2-substituted indole-3-carboxylates $\text{17}$ from aldehydes and the α-phenylsulfonyl-$\text{o}$-aminophenylacetic acid ester derivative $\text{16}$.     

Banach Spaces of Solutions of the Helmholtz Equation in the Plane

The purpose of this article is to study the Hilbert space W²\mathcal{ W}^2 consisting of all solutions of the Helmholtz equation Du+u=0\Delta u+u=0 in \BbbR²\Bbb{R}^2 that are the image under the Fourier transform of L²L^2 densities in the unit circle. We characterize this space as a close subspace of the Hilbert space H²\mathcal{ H}^2 of all functions belonging to L²( | x | ^-3dx) L^2( | x | ^{-3}dx) jointly with their angular and radial derivatives, in the complement of the unit disk in \BbbR²\Bbb{R}^2. We calculate the reproducing kernel of W²\mathcal{ W}^2 and study its reproducing properties in the corresponding spaces H^p\mathcal{H}^p, for $p>1$p>1.     

Activity coefficients at infinite dilution for surfactants

A new alternative is presented for activity coefficients at infinite dilution determination via surface tension data of low vapour pressure substances. It was found that experimental data for surfactants follows Volmer's surface equation of state behaviour over the diluted region until the critical micelle concentration. The key operations are: the choice of the same standard conditions for the bulk and the surface phases, the combination of Gibbs and Volmer equations and the use of the symmetric activity coefficients convention. An exact relation between the activity coefficient at infinite dilution and the reciprocal of the critical micelle mole fraction was found which allowed us the verification of the model.     

Quotient polytopes of cyclic polytopes part I: Structure and characterization

We investigate the quotient polytopesC/F, whereC is a cyclic polytope andF is a face ofC. We describe the combinatorial structure of such quotients, and show that under suitable restrictions the pair (C, F) is determined by the combinatorial type ofC/F. We describe alternative constructions of these quotients by “splitting vertices” of lower-dimensional cyclic polytopes. Using Gale diagrams, we show that every simpliciald-polytope withd+3 vertices is isomorphic to a quotient of a cyclic polytope.     

Synthesis of a Helical Bilayer Nanographene

A rigid, inherently chiral bilayer nanographene has been synthesized as both the racemate and enantioenriched M isomer (with 93 % ee) in three steps from established helicenes. This folded nanographene is composed of two hexa‐peri‐hexabenzocoronene layers fused to a [10]helicene, with an interlayer distance of 3.6 Å as determined by X‐ray crystallography. The rigidity of the helicene linker forces the layers to adopt a nearly aligned AA‐stacked conformation, rarely observed in few‐layer graphene. By combining the advantages of nanographenes and helicenes, we have constructed a bilayer system of 30 fused benzene rings that is also chiral, rigid, and remains soluble in common organic solvents. We present this as a molecular model system of bilayer graphene, with properties of interest in a variety of potential applications.     

Structural characterization of a lariat ether based on 4,10-diaza-2,3,11,12-dibenzo-18-crown-6 and of a coordination Pb(II) complex using picrate as co-ligand

A new lariat ether, N,N′-di(methylenecarboxyethoxy)-4,10-diaza-2,3,11,12-dibenzo-18-crown-6, C₂₈H₃₈N₂O₈, has been characterized and tested for Pb²⁺ extraction in a picrate medium. The isolated complex, [(picrato-O,O′)-(N,N′-di-methylenecarboxyethoxy-4,10-diaza-2,3,11,12-dibenzo-18-crown-6)]-lead(II) picrate, [C₃₄H₄₀N₅O₁₅Pb]⁺[C₆H₂N₃O₇]⁻, includes a 7-coordinated Pb²⁺ cation complex where sidearms of the macrocycle are involved in complexation, with Pb‐O bond lengths of 2.587(4) and 2.617(4) ?. Picrate ions serve both as co-ligand and as anion for charge balance. Both free ligand and Pb²⁺ complex have been X-ray characterized: a = 18.4723(16), b = 24.0057(19), c = 14.4309(14) ?, β = 112.962(7)°, P2₁/c, for the ligand; a = 12.7591(15), b = 21.951(2), c = 16.4389(15) ?, β = 97.144(8)°, P2₁/n, for the complex.