Impact of polyphenols on receptor-ligand interactions by NMR: the case of neurotensin (NT)-neurotensin receptor fragment (NTS1) complex.

Ligand-receptor interactions can be implicated in many pathological events such as chronic neurodegenerative diseases. Thus, the discovery of molecules disrupting this type of interactions could be an interesting therapeutic approach. Polyphenols are well known for their affinity for proteins and several studies have characterized these direct interactions.

Gallotannins and Tannic Acid: First Chemical Syntheses and In Vitro Inhibitory Activity on Alzheimer's Amyloid β-Peptide Aggregation.

The screening of natural products in the search for new lead compounds against Alzheimer's disease has unveiled several plant polyphenols that are capable of inhibiting the formation of toxic β-amyloid fibrils. Gallic acid based gallotannins are among these polyphenols, but their antifibrillogenic activity has thus far been examined using "tannic acid", a commercial mixture of gallotannins and other galloylated glucopyranoses. The first total syntheses of two true gallotannins, a hexagalloylglucopyranose and a decagalloylated compound whose structure is commonly used to depict "tannic acid", are now described.

Unambiguous Determination of the Absolute Configuration of Dimeric Stilbene Glucosides from the Rhizomes of Gnetum africanum.

Dimeric stilbene glucosides 1-3 [two diastereomers of (-)-gnemonoside A (1a and 1b), (-)-gnemonoside C (2), and (-)-gnemonoside D (3)] as well as a mixture of the two enantiomers of gnetin C (4) were isolated from the rhizomes of Gnetum africanum. The two enantiomers of gnetin C, (+)-4 and (-)-4, were obtained from the aglycones of 1a and 1b, respectively. The configurations of these stilbenoids were investigated by NMR and vibrational circular dichroism (VCD) experiments.

Viniphenol A, a complex resveratrol hexamer from Vitis vinifera stalks: structural elucidation and protective effects against amyloid-β-induced toxicity in PC12 cells.

Stilbenes have received much attention during the last two decades following the discovery of resveratrol in wine. Since then, there have been a growing number of papers reporting various biological activities of naturally occurring stilbenes. The aim of this study was to determine new minor stilbenes from Vitis vinifera stalks.

Bioactive stilbenes from Vitis vinifera grapevine shoots extracts.

Background: Viticultural residues from commercial viticultural activities represent a potentially important source of bioactive stilbenes such as resveratrol. The main aim of the present study was therefore to isolate, identify and perform biological assays against amyloid-β peptide aggregation of original stilbenes from Vitis vinifera shoots.

Results: A new resveratrol oligomer, (Z)-cis-miyabenol C (3), was isolated from Vitis vinifera grapevine shoots together with two newly reported oligostilbenes from Vitis vinifera shoots, vitisinol C (1) and (E)-cis-miyabenol C (2), and six known compounds: piceatannol, resveratrol, (E)-ε-viniferin (trans-ε-viniferin), ω-viniferin, vitisinol C and (E)-miyabenol C.

Centrifugal partition chromatography applied to the isolation of oak wood aroma precursors.

Flavours extracted from oak wood during barrel ageing contribute to the organoleptic character of wines and spirits. The aim of this work was to identify the glycosidic precursors of the key volatile compounds responsible for oak wood aroma. Oak extract is a very complex matrix and, furthermore, precursors are present in very small quantities.

Anthocyanin phytochemical profiles and anti-oxidant activities of Vitis candicans and Vitis doaniana.

Introduction: Grapes are one of the most important fruit crops in the world. The quality of red grape berries greatly depends on skin colour, mainly due to the anthocyanin profile. Today, the American Vitis species have the greatest potential for breeding work.

3D NMR structure of a complex between the amyloid beta peptide (1-40) and the polyphenol ε-viniferin glucoside: implications in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. There is a consensus that Aβ is a pathologic agent and that its toxic effects, which are at present incompletely understood, may occur through several potential mechanisms. Polyphenols are known to have wide-ranging properties with regard to health and for helping to prevent various diseases like neurodegenerative disorders.

Chemical dereplication of wine stilbenoids using high performance liquid chromatography-nuclear magnetic resonance spectroscopy.

Wine is a major dietary source of numerous potentially health promoting stilbenoids that have been the subject of many qualitative and quantitative studies. However, our initial HPLC-MS analyses of crude wine samples demonstrated the presence of compounds with molecular weights matching characteristic stilbenoid dimers, trimers, and tetramers that were unaccounted for in the literature. Due to the likelihood that these are known compounds, a chemical dereplication method is highly desirable.

2-Arylbenzofuran-based molecules as multipotent Alzheimer's disease modifying agents.

The complex etiology of Alzheimer's disease prompts scientists to develop multi-target strategies to combat causes and symptoms. In line with this modern paradigm and as a follow-up to our previous studies, we designed and synthesized a focused collection of new 2-arylbenzofurans and evaluated their biological properties towards specific targets involved in AD, namely human AChE and human BuChE, and Aβ fibril formation. Selected compounds were also tested for their ability to inhibit Aβ neurotoxicity in terms of neuronal viability loss, and to prevent Aβ peptide-binding to cell membrane and intracellular reactive oxygen species (ROS) formation.

Intermolecular interactions between the neurotensin and the third extracellular loop of human neurotensin 1 receptor.

Neurotensin (NT) is a tridecapeptide hormone in the periphery and neurotransmitter in the brain that principally activates three receptor subtypes, named NTS1, NTS2, and NTS3. Since little is known about its structure in the presence of its principal receptor NTS1, we determined it using the key domain of the receptor, i.e.

Isorhapontigenin: a novel bioactive stilbene from wine grapes.

Stilbenes are a family of bioactive compounds found in plants. However, only a few stilbenes are present in the human diet. Grape and wine are the main dietary source of stilbenes, resveratrol and piceid being the most common ones.

Elucidation by NMR solution of neurotensin in small unilamellar vesicle environment: molecular surveys for neurotensin receptor recognition.

Neurotensin (NT) is a tridecapeptide, hormone in the periphery and neurotransmitter in the brain. We used high-resolution nuclear magnetic resonance (NMR) to resolve the three-dimensional structure of NT in a small unilamellar vesicle (SUV) environment. We demonstrate that if the dynamic of the association-dissociation processes of peptide to SUV binding is rapid enough, structural determination can be obtained by solution NMR experiments.

Wine polyphenols: potential agents in neuroprotection.

There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties.

Anthocyanin identification and composition of wild Vitis spp. accessions by using LC-MS and LC-NMR.

The composition and concentration of anthocyanins of grape berry skins were analyzed in order to assess phenotypic variation between four grape wine varieties belonging to 4 different species: Vitis vinifera, Vitis amurensis, Vitis cinerea and Vitis X champinii. High-performance liquid chromatography coupled to mass spectrometry (LC-MS) and NMR spectroscopy (LC-NMR) were used to separate and identify the structure of anthocyanins present in these species. Combination of LC-MS and LC-NMR data resulted in the identification of 33 anthocyanins.

Protective effect of ε-viniferin on β-amyloid peptide aggregation investigated by electrospray ionization mass spectrometry.

Abnormal β-amyloid peptide accumulation and aggregation is considered to be responsible for the formation and cerebral deposition of senile plaques in the brains of patients with Alzheimer's disease (AD). Inhibition of the formation of β-amyloid (Aβ) fibrils would be an attractive therapeutic target for the treatment of AD. Resveratrol and its derivatives exhibit a broad range of pharmacological properties such as protection against cardiovascular diseases and cancers, as well as promoting antiaging effects.

Identification of impact odorants contributing to fresh mushroom off-flavor in wines: incidence of their reactivity with nitrogen compounds on the decrease of the olfactory defect.

Analysis of wines from different grape varieties marked by sometimes intense aromatic nuances of fresh mushroom was performed by gas chromatography coupled with olfactometry. This analysis has led to the identification of several odoriferous zones, which were recalling a fresh mushroom odor. Two trace compounds responsible for these odoriferous zones, 1-nonen-3-one and 1-octen-3-one, have been identified and their content has been determined by using either a multidimensional gas chromatography technique coupled to olfactometry and mass spectrometry detection (in the case of 1-nonen-3-one) or the preparation of the derivative with O-2,3,4,5,6-pentafluorobenzylhydroxylamine hydrochloride in the presence of the deuterated form, as the internal standard (in the case of 1-octen-3-one), then gas chromatography coupled to mass spectrometry detection.

Neuroprotective properties of resveratrol and derivatives.

Stilbenoid compounds consist of a family of resveratrol derivatives. They have demonstrated promising activities in vitro and in vivo that indicate they may be useful in the prevention of a wide range of pathologies, such as cardiovascular diseases and cancers, as well have anti-aging effects. More recently stilbenoid compounds have shown promise in the treatment and prevention of neurodegenerative disorders, such as Huntington's, Parkinson's, and Alzheimer's diseases.

New stilbene dimers against amyloid fibril formation.

Twenty stilbene derivatives and moracin M extracted from natural products were tested against amyloid-beta peptide (Abeta) aggregation. Results of stilbene monomer derivatives indicated that interaction with resveratrol and piceid was specific. Concerning oligomers, scirpusin A and epsilon-viniferin glucoside demonstrated a strong inhibition of the aggregation process.

Design, synthesis, and biological evaluation of new 5-HT4 receptor agonists: application as amyloid cascade modulators and potential therapeutic utility in Alzheimer's disease.

Serotonin 5-HT(4) receptor (5-HT(4)R) agonists are of particular interest for the treatment of Alzheimer's disease because of their ability to ameliorate cognitive deficits and to modulate production of amyloid beta-protein (Abeta). However, despite the range of 5-HT(4)R agonists synthesized to date, potent and selective 5-HT(4)R agonists are still lacking. In the present study, two libraries of molecules based on the scaffold of ML10302, a highly specific and partial 5-HT(4)R agonist, were efficiently prepared by parallel supported synthesis and their binding affinities and agonist activities evaluated.

The polyphenol piceid destabilizes preformed amyloid fibrils and oligomers in vitro: hypothesis on possible molecular mechanisms.

Alzheimer's disease (AD) is characterized by deposits of amyloid in various tissues. The neuronal cytotoxicity of Abeta peptides is attributed not only to various mechanisms but also to amyloid fibrils and soluble oligomeric intermediates. Consequently, finding molecules to prevent or reverse the oligomerization and fibrillization of Abeta could be of therapeutic value in the treatment of AD.

Benzofuran-based hybrid compounds for the inhibition of cholinesterase activity, beta amyloid aggregation, and abeta neurotoxicity.

The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multitarget strategies to combat causes and symptoms. We therefore designed, synthesized, and tested new hybrid molecules linking a benzofuran ring to a N-methyl- N-benzylamine through a heptyloxy chain, affording a series of potential multifunctional drugs for AD. The cholinesterase inhibitory activity was extended to the inhibition of Abeta fibril formation for 1, 3, and 5.

New polyphenols active on beta-amyloid aggregation.

New polyphenol classes have been tested against amyloid-beta peptide aggregation. We have identified four novel polyphenols which could be efficient fibril inhibitors in Alzheimer's disease: malvidin and its glucoside and curculigosides B and D. We suggest that molecules with the particular C(6)-linkers-C(6) structure could be potent inhibitors.

NMR solution structure of neurotensin in membrane-mimetic environments: molecular basis for neurotensin receptor recognition.

Neurotensin (NT) is a 13-residue neuropeptide that exerts multiple biological functions in the central and peripheral nervous system. Little is known about the structure of this neuropeptide, and what is known only concerns its C-terminal part. We determined here for the first time the structure of the full-length NT in membrane-mimicking environments by means of classical proton-proton distance constraints derived from solution-state NMR spectroscopy.

Anthocyanone A: a quinone methide derivative resulting from malvidin 3-O-glucoside degradation.

A new compound resulting from the oxidative degradation of maldivin 3-O-glucoside under acid conditions was detected in a wine model solution stored under 90 and 25 degrees C. It was isolated by semipreparative HPLC, and its structure was elucidated by UV-vis spectra, mass spectrometry (LC/MS), and NMR spectroscopy (1-D and 2-D). The compound was identified as 8-beta-d-glucopyranosyl-2,4-dihydroxy-6-oxo-cyclohexa-2,4-dienyl acetic acid (anthocyanone A), which results from nucleophilic attack of hydrogen peroxide to maldivin 3-O-glucoside through a Baeyer-Villiger oxidation followed by other oxidations steps.