Insights into Molecular Interactions and Biological Effect of Natural Stilbenoids at the TRPA1 Ion Channel.

Natural stilbenoids, polyphenolic compounds notably found in Scots pine and Norway spruce, have been shown to exhibit analgesic and anti-inflammatory effects through the TRPA1 channel, making them promising hits for the development of novel agents to treat inflammatory diseases and pain. In this study, we computationally investigated the putative binding sites of natural stilbenoids at the TRPA1 channel. Specifically, we employed molecular docking and MD simulation approaches to explore three known ligand binding sites at TRPA1.

Investigating the Effectiveness of Different Porous Nanoparticles as Drug Carriers for Retaining the Photostability of Pinosylvin Derivative.

Pinosylvin monomethyl ether (PsMME) is a natural compound known for its valuable bioactive properties, including antioxidant and anti-inflammatory effects. However, PsMME's susceptibility to photodegradation upon exposure to ultraviolet (UV) radiation poses a significant limitation to its applications in the pharmaceutical field. This study, for the first time, introduces a strategy to enhance the photostability of PsMME by employing various nanoformulations.

Formation of Tetrahydrofurano-, Aryltetralin, and Butyrolactone Norlignans through the Epoxidation of 9-Norlignans.

Epoxidation of the C=C double bond in unsaturated norlignans derived from hydroxymatairesinol was studied. The intermediate epoxides were formed in up to quantitative conversions and were readily further transformed into tetrahydrofuran, aryltetralin, and butyrolactone products-in diastereomeric mixtures-through ring-closing reactions and intramolecular couplings. For epoxidation, the classical Prilezhaev reaction, using stoichiometric amounts of -chloroperbenzoic acid (CPBA), was used.

Synthesis and Evaluation of Anisomelic acid-like Compounds for the Treatment of HPV-Mediated Carcinomas.

The vast majority of cervical and 75% of oropharyngeal carcinomas are triggered by infection with a type of high-risk oncogenic human papillomavirus (HPV). It is well-known that E6 and E7 oncoproteins are critical for viral-induced cancer, and hence, they represent valuable targets for therapeutic intervention in HPV-mediated cancers. Our earlier research on the cembranoid, anisomelic acid (AA) showed that, AA has the potential to induce apoptosis in HPV cells by the depletion of E6 and E7 oncoproteins.

Tsuji-Wacker-Type Oxidation beyond Methyl Ketones: Reacting Unprotected Carbohydrate-Based Terminal Olefins through the "Uemura System" to Hemiketals and α,β-Unsaturated Diketones.

Aerobic Pd(AcO)/pyridine-catalyzed oxidation of unprotected carbohydrate-based terminal alkenes was studied. In accordance with previous reports, the initial reaction step gave methyl ketones. However, our substrates partially gave subsequent α,β-water elimination and alcohol oxidation to α,β-unsaturated 2,5-diketones.

Oxidative Transformations of Lignans.

Numerous oxidative transformations of lignan structures have been reported in the literature. In this paper we present an overview on the current findings in the field. The focus is put on transformations targeting a specific structure, a specific reaction, or an interconversion of the lignan skeleton.

Chemical characterization of high-molar-mass fractions in a Norway spruce knotwood ethanol extract.

The low-molar-mass (LMM) fraction, only, i.e., the GC-eluting compounds, which are mainly lignans, has been characterized in Norway spruce knotwood hydrophilic extracts previously.

Content, composition, and stereochemical characterisation of lignans in berries and seeds.

In seed extracts of five oilseed species, in bran extracts of three cereal species, and in seed and/or whole berry extracts of 10 berry species, the concentrations of a large number of lignans and the enantiomeric composition of selected lignans were determined. In the case of sesame and hemp seeds, the lignan content and composition of the whole seeds was compared to that of the hulled seeds. The results showed that cloudberry seeds are the third most lignan-rich food source after linseeds and whole sesame seeds, and that most of the berry species analysed were more lignan-rich than the cereal brans.

Lignans as food constituents with estrogen and antiestrogen activity.

Phytoestrogens are plant-derived food ingredients assumed to contribute to the prevention of hormone-dependent cancers, osteoporosis, cardiovascular disease, and menopausal symptoms. Lignans occur in numerous food plants and various structures; they are common constituents of human diet, and estrogen activity has been assessed for lignan metabolites formed in the mammalian intestine. We examined natural lignans and semisynthetic norlignans for estrogen and antiestrogen activity.

A selective de-O-methylation of guaiacyl lignans to corresponding catechol derivatives by 2-iodoxybenzoic acid (IBX). The role of the catechol moiety on the toxicity of lignans.

We report here the first selective de-O-methylation of a large panel of guaiacyl lignans to the corresponding catechol derivatives by using IBX as primary oxidant under green conditions (dimethyl carbonate-H(2)O solvent) through an in situ reduction procedure. The influence of the catechol moiety on the cytotoxicity and genotoxicity of new lignan derivatives has been investigated. The results obtained indicated that the presence of the catechol moiety sharply enhances the clastogenic potential (e.

Identification of lignans by liquid chromatography-electrospray ionization ion-trap mass spectrometry.

The fragmentation pattern of 30 compounds belonging to different classes of the lignan family was studied by liquid chromatography-electrospray ionization ion-trap mass spectrometry. On the basis of the observed fragmentation patterns, identification of different types of lignans was achieved. For example, dibenzylbutyrolactone lignans showed a characteristic fragmentation pathway by the loss of 44 Da (CO(2)) from the lactone moiety, whereas dibenzylbutanediols showed a loss of 48 Da by a combined loss of formaldehyde and water from the 1,4-butanediol moiety.

Chemical studies on antioxidant mechanisms and free radical scavenging properties of lignans.

The antioxidant activity, in terms of radical scavenging capacity, of altogether 15 different lignans was measured by monitoring the scavenging of the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The effect of differences in skeletal arrangement or the degree of oxidation of the lignans was investigated in a structure-activity relationship study. A large variety in the radical scavenging capacities of the different lignans was observed and related to some structural features.

The plant lignans matairesinol and secoisolariciresinol administered to Min mice do not protect against intestinal tumor formation.

The lignans matairesinol (MAT) and secoisolariciresinol (SECO) were fed to Min mice at 0.02% (w/w) in diet to study their effects on intestinal tumor development. The mean number (67 vs.

New lignan metabolites in rat urine.

Ten potential lignan metabolites were quantified in rat urine extracts using liquid chromatography-tandem mass spectrometry. The rats were orally administered with the plant lignans 7-hydroxymatairesinol, matairesinol, lariciresinol or secoisolariciresinol, or with the mammalian lignan enterolactone. The samples were enzymatically hydrolysed and solid-phase extracted before analysis.

Reactions of the natural lignan hydroxymatairesinol in basic and acidic nucleophilic media: formation and reactivity of a quinone methide intermediate.

The chemical properties and synthetic modifications of the natural lignan hydroxymatairesinol in basic and acidic nucleophilic media were studied. Hydroxymatairesinol presumably reacts via a quinone methide and a carbonium ion mechanism under basic and acidic conditions, respectively. In these conditions the benzylic hydroxyl group was displaced by nucleophiles yielding new 7-substituted butyrolactone lignans.

A new lariciresinol-type butyrolactone lignan derived from hydroxymatairesinol and its identification in spruce wood.

When the natural lignan hydroxymatairesinol (1) was treated with an alkaline aqueous solution, it partially rearranged to isomeric forms of a lariciresinol-type butyrolactone lignan. The two major diastereomers formed (2 and 3) were isolated by column and medium-pressure chromatography, and their structures were elucidated by MS and NMR techniques. These previously unknown butyrolactone lignans were identified as naturally occurring in spruce knotwood by GC, GC-MS, and HPLC-ESI MS/MS analyses.

Antioxidant activity of knotwood extractives and phenolic compounds of selected tree species.

The antioxidant potency and the radical scavenging capacity of superoxide and peroxyl radicals were assessed for 13 hydrophilic knotwood extracts of commercially important wood species, or fractions thereof, as well as for five pure wood-derived lignans and the flavonoid taxifolin. The chemical composition of the knotwood extracts was determined by gas chromatography combined with mass spectrometry. Most of the investigated wood species were rich in hydrophilic extractives (10-20% of the dry wood) with one or a few compounds dominating in each extract.

Synthesis of R-(-)-imperanene from the natural lignan hydroxymatairesinol.

A convenient and high yielding method for the synthesis of R-(-)-imperanene, starting from the readily available natural lignan hydroxymatairesinol from Norway spruce, was developed. Hydroxymatairesinol was degraded in strongly basic aqueous conditions to (E)-4-(4-hydroxy-3-methoxyphenyl)-2-(4-hydroxy-3-methoxyphenylmethyl)but-3-enoic acid, which was esterified and then reduced by LiAlH(4) to afford R-(-)-imperanene. The configuration at the crucial stereocenter was preserved in the synthesis, and the obtained product was identified by optical rotation measurements and chiral HPLC analyses as the R-(-)-enantiomer (ee 86-92%).