Search Results (19)

In this study, six club raspberry varieties were examined for their aromatic profiles and sensory qualities, and statistical approaches were used to determine how aroma components affect consumer impressions. Analysis of the aroma’s chemical composition was performed utilizing headspace SPME and GC-MS. MS-DIAL -v5.5.250627 software was used to identify components from commercial libraries, after 10 repetitions for each variety, followed by manual verification. A sensory evaluation of fresh fruits, with 55 volunteers, was statistically analyzed and linked to chemical composition using multivariate analysis and the OPLS-HDA classification method, which was employed for the first time. Tula Magic was scored the highest in the sensory evaluation compared to Adelita, Himbo Top, Glen Dee, San Rafael, and Cascade Harvest. 2-Heptanol (fresh, lemongrass-like, herbal, floral, fruity, green), heptanal (fresh, aldehydic, fatty, green, herbal), and 2-methyl-6-hepten-1-ol (oily-green, herbaceous-citrusy) separated Tula Magic from the other varieties assessed. The same components were recognized in OPLS as positive contributors to the flavor score, while terpenoids like trans-β-ionone, α-ionone, and α,β-dihydro-β-ionone, as well as 2-heptanone, scored slightly lower. This suggests that a fine balance between the individual components is key to the overall aroma sensation. Full article

A drastic alteration in the potency or efficacy of bioactive compounds due to the addition of a single methyl group is known as the magic methyl effect. This effect has been demonstrated in O-methylated flavonoids, which show differences in physical and chemical properties from those of unmethylated flavonoids—O-methylation converts the hydrophilic hydroxy group into a hydrophobic methoxy group. However, differences in the physical and chemical properties between C-methylated and unmethylated flavonoids are smaller than those for O-methylated flavonoids. Therefore, predicting the magic methyl effect in C-methylated flavonoids is challenging. Eucalyptin and 8-desmethyleucalyptin are C-methylated flavonoids isolated from the leaves of plants, such as Eucalyptus sp. and Kalmia latifolia. These compounds contain 5-hydroxy-7,4′-dimethoxyflavone as the core skeleton. Eucalyptin has two C-methyl groups at the C-6 and C-8 positions, whereas 8-desmethyleucalyptin has one C-methyl group at the C-6 position. In this study, we synthesized eucalyptin and assessed its biological activities. The C-8 methyl group caused significant alterations in cytotoxic and antibiofilm activities. Herein, we report the magic methyl effects in eucalyptin, providing a basis for further chemical and biological studies on C-methylated flavonoids. Full article

Background: The protein kinases CLK and ROCK play key roles in cell growth and migration, respectively, and are potential anticancer targets. ROCK inhibitors have been approved by the FDA for various diseases and CLK inhibitors are currently being trialed in the clinic as anticancer agents. Compounds with polypharmacology are desired, especially in oncology, due to the potential for high efficacy as well as addressing resistance issues. In this report, we have identified and characterized novel, boron-containing dual CLK/ROCK inhibitors with promising anticancer properties. Methods: A library of boronic acid-based CLK/ROCKi was synthesized via Povarov/Doebner-type multicomponent reactions. Kinase inhibition screening and cancer cell viability assays were performed to identify the hit compounds. To gain insights into the probable binding modes of the compounds to the kinases, docking studies were performed. Cell cycle analysis, qPCR and immunoblotting were carried out to further characterize the mode(s) of action of the lead candidates. Results: At 25 nM, the top compounds HSD1400 and HSD1791 inhibited CLK1 and 2 and ROCK2 at greater than 70%. While HSD1400 also inhibited CLK4, the C1 methylated analog HSD1791 did not inhibit CLK4. Antitumor effects of the top compounds were evaluated and dose–response analysis indicated potent inhibition of renal cancer and leukemia cell growth. Immunoblotting results indicated that the top compounds induce DNA damage via upregulation of p-H2AX. Moreover, flow cytometry results demonstrated that the top compounds promote cell cycle arrest in the renal cancer cell line, Caki-1. qPCR and immunoblotting analysis upon HSD1791 dosing indicated suppression of cyclin D/Rb oncogenic pathway upon compound treatment. Conclusions: Novel boronic acid-containing pyrazolo[4,3-f]quinoline-based dual CLK/ROCK inhibitors were identified. The so-called “magic methylation” design approach was used to tune CLK selectivity. Additionally, the findings demonstrate potent in vitro anticancer activity of the lead candidates against renal cancer and leukemia. This adds to the growing list of boron-containing compounds that display biological activities. Full article

In this work, the mechanical properties of hydrogels based on linear polyethyleneimine (PEI) chemically crosslinked with ethyleneglycoldiglycidyl ether (EGDE) were improved by the ionic crosslinking with sodium tripolyphosphate (TPP). To this end, the quaternization of the nitrogen atoms present in the PEI structure was conducted to render a network with a permanent positive charge to interact with the negative charges of TPP. The co-crosslinking process was studied by ¹H high-resolution magic angle spinning (¹H HRMAS) NMR and X-ray photoelectron spectroscopy (XPS) in combination with organic elemental analysis and inductively coupled plasma mass spectrometry (ICP-MS). In addition, the mobility and confinement of water molecules within the co-crosslinked hydrogels were studied by low-field ¹H NMR. The addition of small amounts of TPP, 0.03 to 0.26 mmoles of TPP per gram of material, to the PEI-EGDE hydrogel resulted in an increase in the deformation resistance from 320 to 1080%, respectively. Moreover, the adsorption capacity of the hydrogels towards various emerging contaminants remained high after the TPP crosslinking, with maximum loading capacities (q_max) of 77, 512, and 55 mg g⁻¹ at pH = 4 for penicillin V (antibiotic), methyl orange (azo-dye) and copper(II) ions (metal ion), respectively. A significant decrease in the adsorption capacity was observed at pH = 7 or 10, with q_max of 356 or 64 and 23 or 0.8 mg g⁻¹ for methyl orange and penicillin V, respectively. Full article

Binding affinity is a fundamental parameter in drug design, describing the strength of the interaction between a molecule and its target protein. Accurately predicting binding affinity is crucial for the rapid development of novel therapeutics, the prioritization of promising candidates, and the optimization of their properties through rational design strategies. Binding affinity is determined by the mechanism of recognition between proteins and ligands. Various models, including the lock and key, induced fit, and conformational selection, have been proposed to explain this recognition process. However, current computational strategies to predict binding affinity, which are based on these models, have yet to produce satisfactory results. This article explores the connection between binding affinity and these protein-ligand interaction models, highlighting that they offer an incomplete picture of the mechanism governing binding affinity. Specifically, current models primarily center on the binding of the ligand and do not address its dissociation. In this context, the concept of ligand trapping is introduced, which models the mechanisms of dissociation. When combined with the current models, this concept can provide a unified theoretical framework that may allow for the accurate determination of the ligands’ binding affinity. Full article

Recently, we identified a novel mechanism of enzyme inhibition in N-myristoyltransferases (NMTs), which we have named ‘inhibitor trapping’. Inhibitor trapping occurs when the protein captures the small molecule within its structural confines, thereby preventing its free dissociation and resulting in a dramatic increase in inhibitor affinity and potency. Here, we demonstrate that inhibitor trapping also occurs in the kinases. Remarkably, the drug imatinib, which has revolutionized targeted cancer therapy, is entrapped in the structure of the Abl kinase. This effect is also observed in p38α kinase, where inhibitor trapping was found to depend on a ‘magic’ methyl group, which stabilizes the protein conformation and increases the affinity of the compound dramatically. Altogether, these results suggest that inhibitor trapping is not exclusive to N-myristoyltransferases, as it also occurs in the kinase family. Inhibitor trapping could enhance the binding affinity of an inhibitor by thousands of times and is as a key mechanism that plays a critical role in determining drug affinity and potency. Full article

One of the key scientific aspects of small-molecule drug discovery and development is the analysis of the relationship between its chemical structure and biological activity. Understanding the effects that lead to significant changes in biological activity is of paramount importance for the rational design and optimization of bioactive molecules. The “methylation effect”, or the “magic methyl” effect, is a factor that stands out due to the number of examples that demonstrate profound changes in either pharmacodynamic or pharmacokinetic properties. In many cases, this has been carried out rationally, but in others it has been the product of serendipitous observations. This paper summarizes recent examples that provide an overview of the current state of the art and contribute to a better understanding of the methylation effect in bioactive small-molecule drug candidates. Full article

Solid salts of the divinyl chloronium (C₂H₃)₂Cl⁺ cation (I) and unsaturated C₄H₆Cl⁺ and C₄H₇⁺ carbocations with the highly stable CHB₁₁Hal₁₁⁻ anion (Hal=F, Cl) were obtained for the first time. At 120 °C, the salt of the chloronium cation decomposes, yielding a salt of the C₄H₅⁺ cation. This thermally stable (up to 200 °C) carbocation is methyl propargyl, CH≡C-C⁺-H-CH₃ (VI), which, according to quantum chemical calculations, should be energetically much less favorable than other isomers of the C₄H₇⁺ cations. Cation VI readily attaches HCl to the formal triple C≡C bond to form the CHCl=CH-C⁺H-CH₃ cation (VII). In infrared spectra of cations I, VI, and VII, frequencies of C=C and C≡C stretches are significantly lower than those predicted by calculations (by 400–500 cm⁻¹). Infrared and ¹H/¹³C magic-angle spinning NMR spectra of solid salts of cations I and VI and high-resolution ¹H/¹³C NMR spectra of VII in solution in SO₂ClF were interpreted. On the basis of the spectroscopic data, the charge and electron density distribution in the cations are discussed. Full article

Polymerized, functionalized solution styrene–butadiene rubber (F-SSBR) is a new type of polymerized styrene–butadiene rubber solution containing specific terminal groups, which can be used in treads for high performances. However, the wet skid resistance related to safety, the rolling resistance to energy consumption, and the wear resistance to service life are often contradictory and form the performance “magic triangle”. In this work, oligomeric resins, including Coumarone resin, C₉ resin, C₅/C₉ resin and a styrene-α-methyl styrene copolymer (SSC), were used as tire functional additives and selected to replace treated distillate aromatic extract (TDAE) to improve the performances of silica-filled F-SSBR composites. The C₉ resin, C₅/C₉ resin and SSC could enhance the modulus at 300% and tensile strength of the F-SSBR composite. The four resins could improve the wet skid resistance and wear resistance of the composites. However, Coumarone resin caused poor silica dispersion in the F-SSBR matrix and eventually, the lower modulus, higher loss factor at 60 °C and the higher heat buildup in the composite were comparative to the composite with TDAE. Furthermore, the synergistic effect of the C₅/C₉ resin and SSC was found to improve the mechanical performance of the composites and it resulted in higher tensile strength and modulus, and a lower heat buildup, compared to the case when only TDAE was used. It is noted that the properties “magic triangle” was broken by the C₅/C₉ resin and SSC, and the C₅/C₉10T15 increased the wet skid resistance by 21.7%, fuel-saving rate by 2.3%, and wear resistance by 8.3%, while S20T5 increased the wet skid resistance by 30.4%, fuel-saving rate by 7%, and wear resistance by 25% compared with CG. Full article

C−H methylation of sp² and sp³ carbon centers is significant in many biological processes. Methylated drug candidates show unique properties due to the change in solubility, conformation and metabolic activities. Several photo-catalyzed, electrochemical, mechanochemical and metal-free techniques that are widely utilized strategies in medicinal chemistry for methylation of arenes and heteroarenes have been covered in this review. Full article

There is a considerable practical interest in discovering new ways to obtain organomolybdenum heterogeneous catalysts for olefin epoxidation that are easier to recover and reuse and display enhanced productivity. In this study, the complex salt (H₂pytz)[MoO₂Cl₂(pytz)] (1) (Hpytz = 5-(2-pyridyl)tetrazole) has been prepared, structurally characterized, and employed as a precursor for the hydrolysis-based synthesis of a microcrystalline molybdenum oxide/organic hybrid material formulated as [MoO₃(Hpytz)] (2). In addition to single-crystal X-ray diffraction (for 1), compounds 1 and 2 were characterized by FT-IR and Raman spectroscopies, solid-state ¹³C{¹H} cross-polarization (CP) magic-angle spinning (MAS) NMR, and scanning electron microscopy (SEM). Compounds 1 and 2 were evaluated as olefin epoxidation catalysts using the model reaction of cis-cyclooctene (Cy8) with tert-butyl hydroperoxide (TBHP), at 70 °C, which gave 100% epoxide selectivity up to 100% conversion. While 1 behaved as a homogeneous catalyst, hybrid 2 behaved as a heterogeneous catalyst and could be recovered for recycling without showing structural degradation or loss of catalytic performance over consecutive reaction cycles. The substrate scope was broadened to monoterpene DL-limonene (Lim) and biobased unsaturated fatty acid methyl esters, methyl oleate (MeOle), and methyl linoleate (MeLin), which gave predominantly epoxide products. Full article

Electrolytes based on ionic liquids (IL) are promising candidates to replace traditional liquid electrolytes in electrochemical systems, particularly in combination with carbon-based porous electrodes. Insight into the dynamics of such systems is imperative for tailoring electrochemical performance. In this work, 1-Methyl-1-propylpyrrolidinium bis(trifluoromethylsulfonyl)imide and 1-Hexyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide were studied in a carbon black (CB) host using spectrally resolved Carr-Purcell-Meiboom-Gill (CPMG) and 13-interval Pulsed Field Gradient Stimulated Echo (PFGSTE) Magic Angle Spinning Nuclear Magnetic Resonance (MAS-NMR). Data were processed using a sensitivity weighted Laplace inversion algorithm without non-negativity constraint. Previously found relations between the alkyl length and the aggregation behavior of pyrrolidinium-based cations were confirmed and characterized in more detail. For the IL in CB, a different aggregation behavior was found compared to the neat IL, adding the surface of a porous electrode as an additional parameter for the optimization of IL-based electrolytes. Finally, the suitability of MAS was assessed and critically discussed for investigations of this class of samples. Full article

With a high potential to generate biomass, maize stover arises as an outstanding feedstock for biofuel production. Maize stover presents the added advantage of being a multiple exploitation of the crop as a source of food, feed, and energy. In this study, contrasting groups of recombinant inbred lines (RILs) from a maize multiparent advanced generation intercross (MAGIC) population that showed variability for saccharification efficiency were screened by FTIR-ATR spectroscopy to explore compositional differences between high and low saccharification yielders. High and low saccharification efficiency groups differed in cell wall compositional features: high saccharification RILs displayed higher proportions of S subunits, aromatic compounds, and hemicellulose as opposed to low saccharification efficiency groups in which FTIR predicted higher proportions of lignin, more precisely lignin being richer in subunits G, and greater proportions of crystalline cellulose and acetyl methyl esters. The application of FTIR-ATR spectroscopy in this material allowed us to obtain a rapid and broad vision of cell wall compositional features in contrasting groups of saccharification efficiency. These results helped us to deepen our knowledge into the relationship between cell wall composition and biorefining potential; they also allowed us to establish new targets for future research regarding lignocellulosic bioconversion. Full article

Polymer networks were prepared by Steglich esterification using poly(sorbitol adipate) (PSA) and poly(sorbitol adipate)-graft-poly(ethylene glycol) mono methyl ether (PSA-g-mPEG₁₂) copolymer. Utilizing multi-hydroxyl functionalities of PSA, poly(ethylene glycol) (PEG) was first grafted onto a PSA backbone. Then the cross-linking of PSA or PSA-g-mPEG₁₂ was carried out with disuccinyl PEG of different molar masses (Suc-PEG_n-Suc). Polymers were characterized through nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). The degree of swelling of networks was investigated through water (D₂O) uptake studies, while for detailed examination of their structural dynamics, networks were studied using ¹³C magic angle spinning NMR (¹³C MAS NMR) spectroscopy, ¹H double quantum NMR (¹H DQ NMR) spectroscopy, and ¹H pulsed field gradient NMR (¹H PFG NMR) spectroscopy. These solid state NMR results revealed that the networks were composed of a two component structure, having different dipolar coupling constants. The diffusion of solvent molecules depended on the degree of swelling that was imparted to the network by the varying chain length of the PEG based cross-linking agent. Full article

Psilocybin-containing mushrooms, commonly known as magic mushrooms, have been used since ancient and recent times for depression and to improve quality of life. However, their anti-inflammatory properties are not known. The study aims at investing cytotoxicity; antioxidant; and, for the first time, anti-inflammatory effects of Psilocybe natalensis, a psilocybin-containing mushroom that grows in South Africa, on lipopolysaccharide-induced RAW 264.7 macrophages. Macrophage cells were stimulated with lipopolysaccharide and treated with different concentrations of Psilocybe natalensis mushroom extracted with boiling hot water, cold water and ethanol over 24 h. Quercetin and N-nitro-L-arginine methyl ester were used as positive controls. Effects of extracts on the lipopolysaccharide-induced nitric oxide, prostaglandin E₂, and cytokine activities were investigated. Phytochemical analysis, and the antioxidant and cytotoxicity of extracts, were determined. Results showed that the three extracts inhibited the lipopolysaccharide-induced nitric oxide, prostaglandin E₂, and interleukin 1β cytokine production significantly in a dose-dependent manner close to that of the positive controls. A study proposed that ethanol and water extracts of Psilocybe natalensis mushroom were safe at concentrations used, and have antioxidant and anti-inflammatory effects. Phytochemical analysis confirmed the presence of natural antioxidant and anti-inflammatory compounds in the mushroom extracts. Full article