Synthesis and quantification of oligoesters migrating from starch-based food packaging materials.

The term oligomer refers to structurally diverse compounds coming from incomplete polymerisation or polymer degradation. Their ability to migrate into foodstuffs along with recent studies about their bioavailability and toxicity have risen concerns about the scarcity of standards needed to perform thorough analytical and toxicological studies. In this work, migration extracts of three starch-based biopolymers films for the packaging of fruits and vegetables were analysed according to European legislation 10/2011.

A new synthetic route towards multifunctionalized cyclic amidrazones for feeding chemical space.

In the context of growing impetus to develop new molecular scaffolds as well as a variety of 3D fragments to escape from flatland, we have reintroduced the accessibility of the underexplored azaheterocyclic amidrazones as promising bioisosteres. Herein, we present an original and versatile approach to synthesize cyclic amidrazones functionalized at different positions of the scaffold in view of diversifying the substitution pattern towards multifunctionalization, extension or fusion of the ring system and 3D-shaping of fragments. This unprecedented synthetic route represents a sweet achievement to cover further lead-like chemical space.

An attempt to prepare sulfonyl analogues of fotemustine: unexpected rearrangement to sulfamate during nitrosation step.

This paper describes a flexible strategy to access diethyl ((((-(2-chloroethyl)--nitrososulfamoyl)amino)arylmethyl) phosphonates, as aryl analogues of fotemustine. The new aryl sulfamidophosphonates prepared from 2-chloroethylamine were successfully obtained under eco-environmental conditions using ultrasound irradiation. These compounds did not produce the expected nitroso analogues of fotemustine after the nitrosation reaction but the corresponding sulfamates which were fully characterized.

Synthesis and biological evaluation of DIDS analogues as efficient inhibitors of RAD51 involved in homologous recombination.

RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study.

Identification of sulfonamide compounds active on the insect nervous system: Molecular modeling, synthesis and biological evaluation.

Insect nicotinic acetylcholine receptors (nAChRs) are a recognized target for insecticide design. In this work, we have identified, from a structure-based approach using molecular modeling tools, ligands with potential selective activity for pests versus pollinators. A high-throughput virtual screening with the Openeye software was performed using a library from the ZINC database, thiacloprid being used as the target structure.

Impairments in learning and memory performances associated with nicotinic receptor expression in the honeybee Apis mellifera after exposure to a sublethal dose of sulfoxaflor.

Sulfoxaflor is a new insecticide which acts on the nicotinic acetylcholine receptor (nAChRs) in a similar way to neonicotinoids. However, sufloxaflor (SFX) is thought to act in a different manner and is thus proposed as an alternative in crop protection. The goal of this study is to evaluate the toxicity of SFX and its sublethal effect on the honeybee Apis mellifera after acute exposure.

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression.

The young population, which is particularly at risk of sepsis, is, paradoxically, rarely studied. Acute stimulation of O-GlcNAcylation, a post-translational modification involved in metabolic regulation, cell survival and stress response, is beneficial in young rats with sepsis. Considering that sepsis impacts the gene expression profile and that O-GlcNAcylation is a regulator of transcription, the aims of this study are to (i) unveil beneficial mechanisms of O-GlcNAcylation and (ii) decipher the relationship between O-GlcNAcylation and transcription during sepsis.

Thorough investigation of non-volatile substances extractible from inner coatings of metallic cans and their occurrence in the canned vegetables.

Since the decline of the use of bisphenol A, the chemistry of the varnishes and coatings which are applied to the inner surfaces of metallic food contact materials is poorly documented. We hypothesised that can coatings are now diverse and bring forth various non-intentionally added substances (NIAS) to be described. Investigating complex components such as NIAS requires demanding non-targeted approaches.

Synthesis of novel -nucleoside analogues bearing an anomeric cyano and a 1,2,3-triazole nucleobase as potential antiviral agents.

A linear sequence to access a novel series of -nucleosides bearing a quaternary carbon at the anomeric position tethered to a 4-substituted 1,2,3-triazole ring is described. Most of the compounds were obtained from a -1 alkynyl furanoside, by a tandem or two-step CuAAC/functionalisation sequence, along with a diastereoselective cyanation of the furanoside derivatives in acidic conditions.

Rational modification, synthesis and biological evaluation of N-substituted phthalazinone derivatives designed to target interleukine-15 protein.

Interleukin (IL)-15 is a pleiotropic cytokine structurally close to IL-2 and sharing with the IL-2Rβ and γc receptor (R) subunits. IL-15 plays important roles in innate and adaptative immunity, supporting the activation and proliferation of NK, NK-T, and CD8 T cells. Over-expression of IL-15 has been shown to participate to the development of inflammatory and autoimmune diseases and diverse T cell malignancies.

A regioselective C7 bromination and C7 palladium-catalyzed Suzuki-Miyaura cross-coupling arylation of 4-substituted NH-free indazoles.

A direct and efficient regioselective C7-bromination of 4-substituted 1-indazole has been achieved. Subsequently, a successful palladium-mediated Suzuki-Miyaura reaction of C7-bromo-4-substituted-1-indazoles with boronic acids has been performed under optimized reaction conditions. A series of new C7 arylated 4-substituted 1-indazoles was obtained in moderate to good yields.

Protein O-GlcNAcylation levels are regulated independently of dietary intake in a tissue and time-specific manner during rat postnatal development.

Aim: Metabolic sources switch from carbohydrates in utero, to fatty acids after birth and then a mix once adults. O-GlcNAcylation (O-GlcNAc) is a post-translational modification considered as a nutrient sensor. The purpose of this work was to assess changes in protein O-GlcNAc levels, regulatory enzymes and metabolites during the first periods of life and decipher the impact of O-GlcNAcylation on cardiac proteins.

Synergic effect of a quinuclidine benzamide complexed with borane, the LMA10233, in combination with seven pesticides.

Some quinuclidine benzamide compounds have been found to modulate nicotinic acetylcholine receptors in both mammals and insects. In particular, the quaternarization of 3-amino quinuclidine benzamide derivatives with dichloromethane gave charged N-chloromethylated quinuclidine compounds, disclosing an antagonist profile on homomeric α7 nAChRs. Here, we synthesized and studied the toxicological effect of LMA10233, a quinuclidine-borane complex analogue, the LMA10233, on the pea aphid Acyrthosiphon pisum and found that LMA10233 only exhibit proper toxicity on A.

Gap-134, a Connexin43 activator, prevents age-related development of ventricular fibrosis in Scn5a mice.

Down-regulation of Connexin43 (Cx43) has often been associated with the development of cardiac fibrosis. We showed previously that Scn5a heterozygous knockout mice (Scn5a), which mimic familial progressive cardiac conduction defect, exhibit an age-dependent decrease of Cx43 expression and phosphorylation concomitantly with activation of TGF-β pathway and fibrosis development in the myocardium between 45 and 60 weeks of age. The aim of this study was to investigate whether Gap-134 prevents Cx43 down-regulation with age and fibrosis development in Scn5a mice.

Second Coordination Sphere Effects in an Evolved Ru Complex Based on Highly Adaptable Ligand Results in Rapid Water Oxidation Catalysis.

A new Ru complex containing the deprotonated 2,2':6',2''-terpyridine-6,6''-diphosphonic acid (HtPa) and pyridine (py) of general formula [Ru(HtPa-κ-NO)(py)], , has been prepared and thoroughly characterized by means of spectroscopic and electrochemical techniques, X-ray diffraction analysis, and density functional theory (DFT) calculations. Complex presents a dynamic behavior in the solution that involves the synchronous coordination and the decoordination of the dangling phosphonic groups of the tPa ligand. However, at oxidation state IV, complex becomes seven coordinated with the two phosphonic groups now bonded to the metal center.

Lipidic synthetic alkaloids as SK3 channel modulators. Synthesis and biological evaluation of 2-substituted tetrahydropyridine derivatives with potential anti-metastatic activity.

Small Conductance Calcium (Ca)-activated potassium (K) channels (SKCa) are now proved to be involved in many cancer cell behaviors such as proliferation or migration. The SK3 channel isoform was particularly described in breast cancer where it can be associated with the Orai1 Ca channel to form a complex that regulates the Ca homeostasis during tumor development and acts as a potent mediator of bone metastases development in vivo. Until now, very few specific blockers of Orai1 and/or SK3 have been developed as potential anti-metastatic compounds.

Binding of Sulfoxaflor to -AChBP: Computational Insights from Multiscale Approaches.

Structural features and binding properties of sulfoxaflor (SFX) with -AChBP, the surrogate of the insect nAChR ligand binding domain (LBD), are reported herein using various complementary molecular modeling approaches (QM, molecular docking, molecular dynamics, and QM/QM'). The different SFX stereoisomers show distinct behaviors in terms of binding and interactions with -AChBP. Molecular docking and Molecular Dynamics (MD) simulations highlight the specific intermolecular contacts involved in the binding of the different SFX isomers and the relative contribution of the SFX functional groups.

Mode of action of sulfoxaflor on α-bungarotoxin-insensitive nAChR1 and nAChR2 subtypes: Inhibitory effect of imidacloprid.

Cockroach neurosecretory cells, dorsal unpaired median (DUM) neurons, express two distinct α-bungarotoxin-insensitive nicotinic acetylcholine receptor subtypes, nAChR1 and nAChR2 which are differently sensitive to the neonicotinoid insecticides and intracellular calcium pathways. The aim of this study is to determine whether sulfoxaflor acts as an agonist of nAChR1 and nAChR2 subtypes. We demonstrated that 1 mM sulfoxaflor induced high current amplitudes, compared to acetylcholine, suggesting that it was a full agonist of DUM neuron nAChR subtypes.

3,4-Dideoxy-3,3,4,4-tetrafluoro- and 4-OH epimeric 3-deoxy-3,3-difluoro-α-GalCer analogues: Synthesis and biological evaluation on human iNKT cells stimulation.

iNKT cells recognize CD1d/α-galactosylceramide (α-GalCer) complexes via their invariant TCR receptor and stimulate the immune response. Many α-GalCer analogues have been investigated to interrogate this interaction. Following our previous work related to the modification of the hydrogen bond network between α-GalCer and CD1d, we have now focused our attention on the synthesis of 3-deoxy-3,3-difluoro- and 3,4-dideoxy-3,3,4,4-tetrafluoro-α-GalCer analogues, and studied their ability to stimulate human iNKT cells.

Function-Oriented Synthesis toward Peloruside A Analogues.

A convergent and rapid synthesis of original C2,C3-unsaturated, C11,C13-keto-enol macrocycles with a peloruside A skeleton has been developed. These original unsaturated macrocycles constitute valuable platforms to access peloruside A analogues with high diversity. The four-fragment strategy implemented features two aldol-type couplings with the central C12-C14 building block TES-diazoacetone and a late-stage ring-closing metathesis.

Di- and heptavalent nicotinic analogues to interfere with α7 nicotinic acetylcholine receptors.

In the field of nicotinic acetylcholine receptors (nAChRs), recognized as important therapeutic targets, much effort has been dedicated to the development of nicotinic analogues to agonize or antagonize distinct homo- and heteropentamers nAChR subtypes, selectively. In this work we developed di- and heptavalent nicotinic derivatives based on ethylene glycol (EG) and cyclodextrin cores, respectively. The compounds showed a concentration dependent inhibition of acetylcholine-induced currents on α7 nAChR expressed by Xenopus oocytes.

Synthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents.

Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways.

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step.

In this paper, a new access to several chiral 3-aminoglycals as potential precursors for glycosylated natural products is reported from a common starting material, (-)-methyl-L-lactate. The stereodivergent strategy is based on the implementation of a ring-closing metathesis of vinyl ethers as key step of reaction sequences developed.

Stereospecific C-Glycosylation by Mizoroki-Heck Reaction: A Powerful and Easy-to-Set-Up Synthetic Tool to Access α- and β-Aryl-C-Glycosides.

A stereospecific Mizoroki-Heck cross-coupling of differently substituted glycals with haloarenes resulting in the exclusive formation of either α- or β-aryl-C-glycosides depending solely on the configuration at C3 was achieved. The reaction was easy to set up because no specific precautions were required concerning moisture or oxygen, and it proceeded by a chirality transfer from C3 to C1. After optimization of cross-coupling conditions, various prepared glycals (7 examples) and arenes (10 examples) were tested, leading stereospecifically to the corresponding aryl-C-glycosides with a carbonyl group at C3, thus opening up new horizons for the total synthesis of glycosylated natural products.