Three series of linear extended benzofuran derivatives associating cyanovinyl unit and electron withdrawing systems such as paracyanophenyl (series 1) or pentafluorophenyl (series 2) moeities or the electron donor 3,4-dimethoxyphenyl (series 3) moiety have been prepared. The donor character of the benzofuran part is carried out either without modifying the conjugation by adding the electron donor methoxy groups to the 5 and 6 positions of the benzofuran (compounds BF2 and BF3) or by increasing the extension of the conjugation with the naphthofuran unit (BF4), and by the insertion of a furan ring between the benzofuran and the cyanovinylene bond (BF5). While all compounds show very low emission in solution, microcrystalline powders of almost all compounds show strong emission under excitation at 350 - 400 nm with emission colors ranging from blue - green to red. It is shown that this variation of the emission colors is essentially due to the type of stacking of the molecules in the solids for series 1 and 2. For series 3, it is above all the extension of the conjugation of the compounds which causes the red shift.
Deoxygenation of Oxiranes by λ3σ3‐Phosphorus Reagents – Computational Mechanistic and Stereochemical Study
The deoxygenation of parent and substituted oxiranes by λ3σ3-phosphorus reagents has been explored in detail, therefore unveiling mechanistic aspects as well as regio- and stereochemical consequences. Attack to a ring C atom is almost always preferred over one-step deoxygenation by direct P-to-O attack. In most cases a carbene transfer occurs as first step, leading to a phosphorane and a carbonyl unit that thereafter react in the usual Wittig fashion via the corresponding λ5σ5-1,2-oxaphosphetane intermediate. Betaines rarely constitute true minima after the first C-attack to oxiranes, at least in the gas-phase. Use of the heavier derivatives AsMe3 and SbMe3 as oxirane deoxygenating reagents was also mechanistically studied. The thermodynamic tendency of λ3σ3-phosphorus reagents to act as oxygen (O-attack) or carbene acceptors (C-attack) was theoretically studied by means of the thermodynamic oxygen-transfer potential (TOP) and the newly defined thermodynamic carbene-transfer potential (TCP) parameters, that were explored in a wider context together with many other acceptor centres.
Catalytic Reaction Mechanism of Bacterial GH92 α‐1,2‐Mannosidase: A QM/MM Metadynamics Study
The catalytic mechanism of a 𝐶𝑎+2-dependent family 92 α- mannosidase, which is abundantly present in human gut flora and malfunctions leading to the lysosomal storage disease a- mannosidosis, has been investigated using quantum mechanics/molecular mechanics and metadynamics methods. Computational efforts show that the enzyme follows a conformational itinerary of 0S2/B2,5 → [B2,5]‡ → 1𝑆5, and the 𝐶𝑎+2 ion serves a dual purpose, as it not only distorts the sugar ring but also plays a crucial role in orchestrating the arrangement of catalytic residues. This orchestration, in turn, contributes to the facilitation of 0S2 conformers for the ensuing reaction. This mechanistic insight is well-aligned with the experimental predictions of the catalytic pathway, and the computed energies are of the same order of magnitude as the experimental estimations. Hence, our results extend the mechanistic understanding of glycosidases.
Hyaluronic Acid/Dipeptide Two‐Component Supramolecular Hydrogels: Synergistic Enhancement of Rheology and ECM Mimetics for Suspended Cell Growth
The combination of polymers and low molecular weight (LMW) compounds is a powerful approach to prepare new supramolecular materials – i.e. hydrogels. Here we prepare two-component hydrogels made by a well-known and biologically-active polymer, hyaluronic acid (HA), and a dipeptide-based supramolecular gelator. We undertake a detailed study of different compositions including macroscopic (hydrogel formation, rheology) and micro/nanoscopic characterization (electron microscopy, X-ray powder diffraction). We observe that the two components mutually benefit in the new material: a minimum amout of HA (1-5 mol% of COOH groups) helps to reduce the polymorphism of the LMW component leading to reproducible hydrogels with improved mechanical properties; the LMW component network holds HA without the need of irreversible covalent crosslinking. These materials have a great potential for biomedical application as, for instance, extracellular matrix mimetics for cell growth. As a proof of concept, we have observed that this material is effective for cell growth in suspension and avoids cell sedimentation even in the presence of competing cell-adhesive surfaces, which can be of interest for advanced cell delivery techniques.
Overcoming Biochemical Limitations of Galactose Oxidase through the Design of a Solid‐Supported Self‐Sufficient Biocatalyst
Galactose Oxidase (GalOx) has gained significant interest in biocatalysis due to its ability for selective oxidation beyond the natural oxidation of galactose. However, the practical application of GalOx has been hindered by the limited availability of active and stable biocatalysts, as well as the inherent biochemical limitations such as oxygen (O2) dependency and the need for activation. In this study, we addressed these challenges by immobilizing GalOx into agarose-based and Purolite supports. Additionally, we identified and quantified the oxygen supply limitation into solid catalysts by intraparticle oxygen sensing showing a trade-off between the amount of protein loaded onto the solid support and the catalytic effectiveness. Furthermore, we coimmobilized a heme-containing protein along with the enzyme to function as an activator. To evaluate the application of the immobilized GalOx, we conducted the oxidation of galactose in an instrumented aerated reactor. The results showcased the efficient performance of the immobilized enzyme in the 8 h reaction cycle. Notably, the GalOx immobilized into dextran sulfate-activated agarose exhibited improved stability, overcoming the need for a soluble activator supply, and demonstrated exceptional performance in galactose oxidation. These findings offer promising prospects for the utilization of GalOx in technical biocatalytic applications.
Essential Oil Composition of Fruits of 8 Ferulago species Growing in Türkiye and Multivariate Statistical Analyses
In this study, the composition of the volatile oils obtained from the fruits of 8 Ferulago species (Ferulago cassia Boiss., F. isaurica Peşmen, F. humilis Boiss., F. macrosciadia Boiss. & Balansa, F. setifolia K.Koch, F. silaifolia (Boiss.) Boiss., F. syriaca Boiss., F. trojana Akalın & Pimenov) growing naturally in Turkey were examined by means of GC/MS and GC-FID and α-pinene was determined to be present in the fruits of four species along with other monoterpenes as major components. Principal Component Analyses (PCA) and Hierarchical Cluster Analysis (HCA) was performed, utilizing ten major components in the eight essential oils. Also, a Venn diagram was used to demonstrate chemotaxonomical variations in the composition of the essential oils of eight Ferulago species.
Triterpenoids from Meehania fargesii with Cytotoxic Activity1
Abstract
In the investigation of Meehania fargesii, eighteen triterpenoids were isolated and identified, including a previously unknown compound with an 13,27-cycloursane skeleton, using techniques like 1D and 2D NMR, and HR-MS. Furthermore, the cytotoxicity of these compounds were evaluated against HCT116, MCF-7, and AGS cell lines using the CCK-8 method to examine their structure–activity relationship. Remarkably, compounds 13 and 16 exhibited higher cytotoxicity across all three cell lines compared to the positive drug. Western blot analysis revealed that these compounds activated apoptosis in HCT116 cells by promoting the Bax protein and inhibiting the Bcl-2 protein. This suggests that compounds 13 and 16 have potential as apoptosis-inducing agents in HCT116 cells.
Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma, Alzheimer’s Disease and Diabetes Mellitus
Abstract
Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones with good yields (85–94 %) and their structures were characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (1H-NMR, 13C-NMR), and High-Resolution Mass Spectroscopy (HR-MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α-Glucosidase (α-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I–II (hCA I–II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the Ki values in the range of 12.73±1.26–93.42±9.44 nM for AChE, 8.48±0.92–25.84±2.59 nM for BChE, 66.17±5.16–818.06±44.41 for α-Glu, 2.56±0.26–88.23±9.72 nM for hCA I, and 1.68±0.14–85.43±7.41 nM for hCA II. Molecular docking study was performed to understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated.
Four New Stilbene Derivatives Isolated from Gnetum latifolium var. funiculare Markgr. and Their Inhibition of NO Production in LPS‐activated RAW264.7 Cells
Abstract
Gnetum latifolium var. funiculare Markgr. is a medicinal plant and widely distributed in mountainous areas of Vietnam. Phytochemical investigation on the trunks of this plant afforded eight stilbene derivatives (1–8) including for new compounds (1–4). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Among the isolates, compounds 1–3 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with the IC50 values ranging from 46.81 to 68.10 μM, compounds 4 and 6 showed weak effects with the IC50 values of 96.57 and 79.46 μM, respectively, compared to that of the positive control compound, dexamethasone (IC50 14.20 μM).
Clove Buds Volatile Compounds: Inhibitory Activity on Mycobacterium Growth and Molecular Docking on Mmr Efflux Pump Drug Resistance
Abstract
Syzygium aromaticum is used in traditional and modern medicine for its various and outstanding pharmacological properties. Here, we studied the chemical composition of hexane extract and non-polar fractions (NPF) obtained from the maceration and fractionation of clove buds, in order to evaluate their in vitro antimycobacterial activity, as well as their contribution against efflux pump (EP) resistance through molecular docking experiments. The gas chromatography-mass spectrometry (GC–MS) analysis of the volatile profiles revealed the presence of eugenol, followed by eugenyl acetate, and β-caryophyllene as common major compounds. According to Resazurin microtiter assay (REMA), Mycobacterium tuberculosis H37Rv strain was sensitive to all volatile samples at concentration range between 10 and 100 μg/mL. The NPF of ethanol extract was the best inhibitor with a MIC=10 μg/mL. The in silico study revealed a strong binding affinity between eugenol and Mmr EP protein (−8.1 Kcal/mol), involving two binding modes of hydrogen bond and π-alkyl interactions. The non-polarity character of clove volatile constituents, and their potential additive or synergistic effects could be responsible for the antimycobacterial activity. In addition, these findings suggest the benefic effect of eugenol in the management of mycobacterium drug resistance, whether as potential inhibitor of Mmr drug EP, or modulator during combination therapy.