DataSheet1.docx

<p>Aim of the study: The aim of the present study was to investigate the effects of phytochemically characterized extracts connected with the traditional use (infusions and ethanolic extracts) of different parts of Syringa vulgaris (common lilac) on the pro-inflammatory functions of neutrophils. Active compounds were isolated from the most promising extract(s) using bioassay-guided fractionation, and their activity and molecular mechanisms of action were determined.</p><p>Methods: The extracts were characterized using a HPLC-DAD- MSⁿ method. The effects on ROS, MMP-9, TNF-α, IL-8, and MCP-1 production by neutrophils were measured using luminol-dependent chemiluminescence and enzyme-linked immunosorbent assay (ELISA) methods. The effects on p38MAPK, ERK1/2, JNK phosphorylation, and NF-kB p65 translocation were determined using western blots.</p><p>Results: The major compounds detected in the extracts and infusions belong to structural groups, including caffeic acid derivatives, flavonoids, and iridoids. All extracts and infusions were able to significantly reduce ROS and IL-8 production. Bioassay-guided fractionation led to the isolation of the following secoiridoids: 2″-epiframeroside, oleonuezhenide, oleuropein, ligstroside, neooleuropein, hydroxyframoside, and framoside. Neooleuropein appeared to be the most active compound in the inhibition of cytokine production by attenuating the MAP kinase pathways.</p><p>Conclusion: The present study demonstrated that common lilac, which is a traditionally used medicinal plant in Europe, is a valuable source of active compounds, especially neooleuropein.</p

π‑Philic Molecular Recognition in the Solid State as a Driving Force for Mechanochemical Formation of Apremilast Solvates and Cocrystals

(<i>S</i>)-<i>N</i>-{2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1<i>H</i>-isoindol-4-yl}­acetamide (Apremilast, APR), a novel anti-inflammatory drug used in psoriasis (Ps) and psoriatic arthritis (PsA) treatment, forms in the solid state well organized structures with a π-philic pocket susceptible to aromatic–aromatic interactions. It has been proven that such specific arrangement is preserved even after melting the APR sample. The empty π-philic APR pocket can be filled with different small molecules (dichloromethane, ethyl acetate, acetonitrile, toluene, benzene, pyridine) by means of mechanochemical grinding forming appropriate solvatomorphs; however, the strong preference for favorable interactions with aromatic species is unquestionable. During grinding of APR with a mixture of solvents (dichloromethane, acetonitrile, toluene), only toluene is embedded into the crystal lattice. Hence, it has been concluded that APR in the solid state behaves as a selective π-philic mechanoreceptor. The strong tendency for π-philic molecular recognition was employed in a mechanochemical process as a driving force for the formation of pharmaceutical cocrystals with coformers, which belong to the group of aromatic natural products (catechol, pyrogallol, resorcinol). The obtained cocrystals were characterized by advanced one-dimensional and two-dimensional solid state NMR techniques, differential scanning calorimetry, and powder X-ray diffraction. The molecular structure of APR/catechol cocrystal was refined employing an NMR crystallography approach, comparing the set of experimental NMR data (¹H δ_iso, ¹³C δ_iso) with computed shielding parameters calculated by means of the GIPAW method

Approach toward the Understanding of Coupling Mechanism for EDC Reagent in Solvent-Free Mechanosynthesis

A unique approach in mechanosynthesis, joining solid-state NMR spectroscopy, X-ray crystallography, and theoretical calculations, is employed for the first time to study the mechanism of the formation of the C–N amide bond using EDC·HCl as a coupling reagent. It has been proved that EDC·HCl, which in the crystal lattice exists exclusively in the cyclic form (X-ray data), easily undergoes transformation to a pseudocyclic stable intermediate in reaction with carboxylic acid forming a low-melt phase (differential scanning calorimetry, solid-state NMR). The obtained intermediate is reactive and can be further used for synthesis of amides in reaction with appropriate amines

Trimeric and Tetrameric A‑Type Procyanidins from Peanut Skins

Peanut skins are a rich source of oligomeric and polymeric procyanidins. The oligomeric fractions are dominated by dimers, trimers, and tetramers. A multistep chromatographic fractionation led to the isolation of four new A-type procyanidins of tri- and tetrameric structures. The structures of the new trimers were defined by NMR, electronic circular dichroism, and MS data as epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin B (<b>3</b>), and epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→6)-catechin, peanut procyanidin C (<b>4</b>). The new tetramers were defined as epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→6)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin E (<b>1</b>), and epicatechin-(4β→8,2β→O→7)-epicatechin-(4β→6)-epicatechin-(4β→8,2β→O→7)-epicatechin, peanut procyanidin F (<b>2</b>). In addition, both A-type dimers A1, epicatechin-(4β→8,2β→O→7)-catechin, and A2, epicatechin-(4β→8,2β→O→7)-epicatechin, as well as two known peanut trimers, <i>ent-</i>epicatechin-(4β→6)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin A (<b>5</b>), and epicatechin-(4β→8)-epicatechin-(4β→8,2β→O→7)-catechin, peanut procyanidin D (<b>6</b>), were also isolated. Dimer A1, the four trimers, and two tetramers were evaluated for anti-inflammatory activity in an in vitro assay, in which LPS-stimulated macrophages were responding with secretion of TNF-α, a pro-inflammatory cytokine. Tetramer F (<b>2</b>) was the most potent, suppressing TNF-α secretion to 82% at 8.7 μM (10 μg/mL), while tetramer E (<b>1</b>) at the same concentrations caused a 4% suppression. The results of the TNF-α secretion inhibition indicate that small structural differences, as in peanut procyanidin tetramers E and F, can be strongly differentiated in biological systems