The Effects of a Cultivar and Production System on the Qualitative and Quantitative Composition of Bioactive Compounds in Spring Wheat (Triticum sp.).

Spelt Triticum aestivum L. subsp. spelta (cv. Wirtas), einkorn Triticum monococcum L. (cv. Samopsza) and emmer Triticum dicoccum Schrank (Schuebl) (cv. Plaskurka biala and Plaskurka ciemna) spring wheat cultivars were analyzed and compared to common wheat Triticum aestivum L. subsp. aestivum (cv. Harenda, Kandela, Mandaryna, Serenada, Goplana, Kamelia, Nimfa, Rusalka, Struna, Zadra) cultivated in an organic production system. Moreover, the performance of four common wheat cultivars (cv. Harenda, Kandela, Mandaryna, Serenada) grown in organic, conventional and integrated production systems were compared. The UHPLC-DAD-MS and TLC-DPPH• analyses of specific substances (phenolic acids and alkylresorcinols) were evaluated to ascertain the potential of spring wheat cultivars for promoting human health and suitability for cultivation in an organic production system. The highest yield was observed for the T. aestivum L. subsp. aestivum (modern hull-less) cv. Nimfa (4.45 t/ha), which also demonstrated the lowest resistance to Fusarium spp. infection. Among the contemporary hull-less cultivars, cv. Mandaryna and cv. Harenda exhibited the highest resistance to this pathogen (2.4% and 3.7% of grains infected by Fusarium, respectively), while simultaneously displaying the highest organic phenolic acid content (900.92 and 984.55 µg/g of the grain) and the highest antioxidant potential. It is noteworthy that the cereal hulls of T. monococcum L. (old hulled) (cv. Samopsza) exhibited a markedly elevated content of phenolic acids (approximately 4000 µg/g of the grain). This may have contributed to the reduced incidence of Fusarium infection (9.3% of grains infected) observed in the grains of this cultivar. Furthermore, the hulls proved to be a rich source of phenolics with high antioxidant activity, which is beneficial for human and animal health.

Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1-15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 µM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

Assessment of 5-Hydroxymethylfurfural in Food Matrix by an Innovative Spectrophotometric Assay.

Foods contaminants pose a challenge for food producers and consumers. Due to its spontaneous formation during heating and storage, hydroxymethylfurfural (HMF) is a prevalent contaminant in foods rich in carbohydrates and proteins. Colorimetric assays, such as the Seliwanoff test, offer a rapid and cost-effective method for HMF quantification but require careful optimization to ensure accuracy. We addressed potential interference in the Seliwanoff assay by systematically evaluating parameters like incubation time, temperature, and resorcinol or hydrochloric acid concentration, as well as the presence of interfering carbohydrates. Samples were analyzed using a UV-Vis spectrophotometer in scan mode, and data obtained were validated using HPLC, which also enabled quantification of unreacted HMF for assessing the protocol's accuracy. Incubation time and hydrochloric acid percentage positively influenced the colorimetric assay, while the opposite effect was observed with the increase in resorcinol concentration. Interference from carbohydrates was eliminated by reducing the acid content in the working reagent. HPLC analyses corroborated the spectrophotometer data and confirmed the efficacy of the proposed method. The average HMF content in balsamic vinegar samples was 1.97 ± 0.94 mg/mL. Spectrophotometric approaches demonstrated to efficiently determine HMF in complex food matrices. The HMF levels detected in balsamic vinegars significantly exceeded the maximum limits established for honey. This finding underscores the urgent need for regulations that restrict contaminant levels in various food products.

Designing a Hypoxia-Activated Sensing Platform Using an Azo Group-Triggered Reaction with the Formation of Silicon Nanoparticles.

Hypoxia is known as a specific signal of various diseases, such as liver fibrosis. We designed a hypoxia-sensitive fluorometric approach that cleaved the azo bond (N═N) in the presence of hypoxia-controlled agents (sodium dithionite and azoreductase). 4-(2-Pyridylazo) resorcinol (Py-N═N-RC) bears a desirable hypoxia-responsive linker (N═N), and its azo bond breakup can only occur in the presence of sodium dithionite and azoreductase and leads to the release of 2,4-dihydroxyaniline, which can react with 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane to generate yellow fluorescent silicon nanoparticles. This approach exhibited high selectivity and sensitivity toward both sodium dithionite and azoreductase over other potential interferences. The mouse liver microsome, which is known to contain azoreductase, was applied and confirmed the feasibility of the designed platform. Py-N═N-RC is expected to be a practical substrate for hypoxia-related biological analyses. Furthermore, silicon nanoparticles were successfully applied for Hela cell imaging owing to their negligible cytotoxicity and superb biocompatibility.

Moment analysis method for determination of rate constants of solute permeation across interface of spherical molecular aggregates by means of high-performance liquid chromatography.

A moment analysis method was developed for the study of solute permeation at the interface of spherical molecular aggregates. At first, new moment equations were developed for determining the partition equilibrium constant (Kp) and permeation rate constants (kin and kout) of solutes from the first absolute (µ1A) and second central (µ2C) moments of elution peaks measured by using high-performance liquid chromatography (HPLC). Then, the method was applied to the analysis of mass transfer phenomena of three solutes, i.e., hydroquinone, resorcinol, and catechol, at the interface of sodium dodecylsulfate (SDS) micelles. HPLC data were measured by using an ODS column and an aqueous phosphate buffer solution (pH = 7.0) as the mobile phase solvent. Pulse response experiments were conducted while changing SDS concentration (5 - 20 mmol dm-3) in the mobile phase under the conditions that the surface of ODS stationary phase was dynamically coated by SDS monomers. In order to demonstrate the effectiveness of the moment analysis method using HPLC, the values of Kp, kin, and kout were determined for the three solutes as 35 - 69, 2.4 × 10-8 - 1.4 × 10-6 m s-1, and 7.0 × 10-10 - 2.1 × 10-8 m s-1, respectively. Their values increase with an increase in the hydrophobicity of the solutes. The method has some advantages for the study of interfacial solute permeation of molecular aggregates. For example, neither immobilization nor chemical modification of both solute molecules and molecular aggregates is required when elution peaks are measured by using HPLC. Interfacial solute permeation takes place in the mobile phase without any chemical reaction or physical action on molecular aggregates. The values of Kp, kin, and kout were analytically determined from those of µ1A and µ2C by using the moment equations. The results of this study must contribute to the dissemination of an opportunity for studying the interfacial solute permeation of molecular aggregates to many researchers because of extremely high versatility of HPLC.

Indicator displacement-based colorimetric assay for dibutyl phthalate in pharmaceutical products with titanium(IV)-pyridylazo resorcinol (PAR).

Taking advantage of the competitive binding affinity towards Ti(IV) between 4-(2-pyridylazo) resorcinol (PAR) and phthalate, a simple indicator displacement (ID)-based colorimetric assay was designed for indirect determination of a well-known phthalic acid ester, dibutyl phthalate (DBP). The indicator PAR and Ti(IV) formed a purplish-red-colored Ti(IV)-PAR complex (λmax = 540 nm) at a 1:1 ratio. In the presence of pre-hydrolyzed DBP, colorless complex formation of phthalate ion (emerging from alkaline hydrolysis of DBP) with Ti(IV) resulted in a hypsochromic shift in absorbance maximum, accompanying a color change from purplish-red to yellowish-orange (λmax = 390 nm) by the release of PAR from Ti(IV)-PAR system. Based on this mechanism, the linear response range of the system for DBP was found to lie between 0.16 and 0.37 mmol L-1 with an experimental detection limit of 11.6 µmol L-1. The recommended Ti(IV)-PAR system was successfully applied to DBP-containing pharmaceutical products (as real sample) after a simple clean-up process for removing possible water-soluble interferents. The analytical results obtained from the recommended method (by applying the standard addition approach) and the reference liquid chromatography-tandem mass spectrometric (LC-MS/MS) method were statistically compared using DBP-extract of the drug samples. Consequently, a simple and selective colorimetric ID strategy was proposed for the analysis of DBP in pharmaceuticals for the first time.

[Development of Organocatalytic Reactions for the Synthesis of Natural Products and Pharmaceuticals].

This review describes novel organocatalytic methods for the enantioselective construction of spiroindans and spirochromans and the application of the methods to the total synthesis of natural products. We developed an intramolecular Friedel-Craftstype 1,4-addition in which the substrates were a resorcinol derivative and 2-cyclohexenone linked by an alkyl chain. The reaction proceeded smoothly in the presence of a cinchonidine-based primary amine (30 mol%) with water and p-bromophenol as additives. A variety of spiroindanes were obtained with high enantioselectivity under these conditions. The reaction was applied in the first total synthesis of the unusual proaporphine alkaloid (-)-misramine, which included the key steps of enantioselective spirocyclization and double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. The total synthesis of misrametine was achieved by selective demethylation of the methoxy group from the precursor to misramine. Next, a method for highly enantioselective organocatalytic construction of spirochromans containing a tetrasubstituted stereocenter was developed. An intramolecular oxy-Michael addition was catalyzed by a bifunctional cinchona alkaloid thiourea catalyst. A variety of spirochroman compounds containing a tetrasubstituted stereocenter were obtained with excellent enantioselectivity of up to 99% enantiomeric excess. The reaction was applied to the asymmetric formal synthesis of (-)-(R)-cordiachromene.

Preparation of molecularly imprinted polymer for the specific adsorption and selective extraction of alkylresorcinols from whole wheat flour.

Alkylresorcinols are important biomarkers for evaluating whole wheat foods. However, their structures encompass a broad spectrum of homologs, making isolating and analyzing individual alkylresorcinol notably challenging. Herein, we synthesized highly selective molecularly imprinted polymers (MIPs) utilizing a facile and cost-effective precipitation polymerization method and 5-heneicosylresorcinol (ARC21:0) as the template molecule. Various crucial preparation parameters were systematically optimized, such as different porogens, functional monomers, imprinting ratios, and polymerization time. The polymers were characterized through scanning electron microscopy and Fourier transform infrared spectroscopy, and their adsorption performances were thoroughly evaluated. MIPs exhibited a notably enhanced adsorption capacity compared with that of non-imprinted polymers, reaching an optimal adsorption amount of 71.75 mg·mL-1 and imprinting factor of 2.02. Altogether, the synthesized MIPs showed superior affinity and selectivity for ARC21:0, as confirmed by their selective extraction, suggesting their potential applications in the analysis, separation, and monitoring of ARC21:0 in whole wheat foods.

Alkylresorcinol detection and identification in archaeological pottery using ultra-high-performance liquid chromatography-quadrupole/Orbitrap mass spectrometry.

RATIONALE: Alkylresorcinols (AR) are cereal-specific biomarkers and have recently been found in archaeological pots. However, their low concentrations and high susceptibility to degradation make them difficult to detect using conventional gas chromatography mass spectrometry (GC/MS). Here we describe the development of a more sensitive liquid chromatography mass spectrometry (LC/MS) method to detect these compounds. METHOD: A method based on the use of ultra-high-performance liquid chromatography (UHPLC) coupled to an Orbitrap mass analyser was established and validated for the detection of low-concentration ARs in pottery. During the preliminary experiments, UHPLC-Q/Orbitrap MS (ultra-high-performance liquid chromatography-quadrupole/Orbitrap mass spectrometry) was demonstrated to be more sensitive, and a wide range of AR homologues in cereal extracts were detected, unlike UHPLC-QTOFMS (ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry) and GC/MS. The developed method was utilised to profile AR homologue distribution in modern cereal samples and reanalyse AR-containing pots from the archaeological site of Must Farm. RESULTS: A highly sensitive LC/MS method with a limit of detection (LOD) of 0.02 µg/g and a limit of quantification (LOQ) of 0.06 µg/g was used to profile ARs in five modern cereal grains. The obtained LOD is 250 times lower than that obtained using the conventional GC/MS approach. AR 21:0 was the most abundant homologue in all four Triticum spp.-einkorn, emmer, Khorasan wheat and common wheat. Meanwhile, AR 25:0 was the predominant homologue in barley, potentially enabling differentiation between wheat and barley. The developed LC/MS-based method was successfully used to analyse ARs extracted from Must Farm potsherds and identified the cereal species most likely processed in the pots-emmer wheat. CONCLUSION: The described method offers an alternative and more sensitive approach for detecting and identifying ARs in ancient pottery. It has been successfully utilised to detect AR homologues in archaeological samples and discriminate which cereal species-wheat and barley-were processed in the pots.

Comprehensive analysis of resorcinyl-imidazole Hsp90 inhibitor design.

Human Hsp90 chaperones are implicated in various aspects of cancer. Due to this, Hsp90 has been explored as potential target in cancer treatment. Initial attempts to use Hsp90 inhibitors in drug trials failed due to toxicity and inefficacy. The next generation of drugs were less toxic but still insufficiently effective in a clinical setting. Recently, a lot of effort is being put into understanding the consequences of Hsp90 isoform selective inhibition, expecting that this might hold the key in targeting Hsp90 for disease treatment. Here we investigate a series of compounds containing the aryl-resorcinol scaffold with a 5-membered ring as a promising class of new human Hsp90 inhibitors, reaching nanomolar affinity. We compare how the replacement of 5-membered ring, from thiadiazole to imidazole, as well as a variety of their substituents, influences the potency of these inhibitors for Hsp90 alpha and beta isoforms. To further elucidate the dissimilarity in ligand selectivity between the isoforms, a mutant protein was constructed and tested against the ligand library. In addition, we performed a series of molecular dynamics (MD) and docking simulations to further explain our experimental findings as well as evaluated key compounds in cell assays. Our results deepen the understanding of Hsp90 isoform ligand selectivity and serve as an informative base for further Hsp90 inhibitor optimization.

Molecularly Imprinted Electrochemical Sensor Based on α-Cyclodextrin Inclusion Complex and MXene Modification for Highly Sensitive and Selective Detection of Alkylresorcinols in Whole Wheat Foods.

Authenticating whole wheat foods poses a significant challenge for both the grain industry and consumers. Alkylresorcinols (ARs), serving as biomarkers of whole wheat, play a crucial role in assessing the authenticity of whole wheat foods. Herein, we introduce a novel molecularly imprinted electrochemical sensor with modifications involving a molecularly imprinted polymer (MIP) and MXene nanosheets, enabling highly sensitive and selective detection of ARs. Notably, we specifically chose 5-heneicosylresorcinol (AR21), the predominant homologue in whole wheat, as the template molecule. α-Cyclodextrin and acrylamide served as dual functional monomers, establishing a robust multiple interaction between the MIP and AR21. As a result, the sensor exhibited a wide linear range of 0.005 to 100 µg·mL-1 and a low detection limit of 2.52 ng·mL-1, demonstrating exceptional selectivity and stability. When applied to commercial whole wheat foods, the assay achieved satisfactory recoveries and accuracy, strongly validating the practicality and effectiveness of this analytical technique.

Silver ion chromatography enables the separation of 2-methylalkylresorcinols from alkylresorcinols.

Alkylresorcinols (∑ARs) is the generic term for a highly varied class of lipids found mainly in cereals. These bioactive compounds consist mainly of 5-alkylresorcinols (ARs), which differ in length, unsaturation, and substituents on the alkyl side chain on C-5. In addition, 2-methyl-5-alkylresorcinols (mARs) are scarcely studied minor compounds that are supposed to exist with the same structural diversity. In the first step, ∑ARs were enriched by solid-phase extraction from wheat grain and quinoa seed extracts. The subsequent application of silver ion chromatography (SIC), silica gel, coated with 20% AgNO3 , then deactivated with 1% water) enabled an unprecedented full separation of saturated mARs from conventional ARs. Specifically, saturated mARs were eluted with n-hexane/ethyl acetate (92:8, v/v), and conventional ARs with n-hexane/ethyl acetate (80:20, v/v). The unpreceded separation indicated that the SIC method could be useful not only for separations according to the degree of unsaturation, but also in the case of steric hindrance by additional (alkyl) substituents. Continued fractionation enabled the collection of unsaturated ARs in wheat and quinoa extracts. In this way, 35 ∑ARs (including five mARs) were detected by gas chromatography/mass spectrometry analysis in wheat and 45 ∑ARs (including 21 mARs) in quinoa. These included several low abundant and partly unknown ∑ARs such as 1,3-dihydroxy-5-tricosadienylbenzene.

Identification of a novel extracellular inhibitor of FGF2/FGFR signaling axis by combined virtual screening and NMR spectroscopy approach.

The aberrant activation of the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor (FGFR) signalling pathway drives severe pathologies, including cancer development and angiogenesis-driven pathologies. The perturbation of the FGF2/FGFR axis via extracellular allosteric small inhibitors is a promising strategy for developing FGFR inhibitors with improved safety and efficacy for cancer treatment. We have previously investigated the role of new extracellular inhibitors, such as rosmarinic acid (RA), which bind the FGFR-D2 domain and directly compete with FGF2 for the same binding site, enabling the disruption of the functional FGF2/FGFR interaction. To select ligands for the previously identified FGF2/FGFR RA binding site, NMR data-driven virtual screening has been performed on an in-house library of non-commercial small molecules and metabolites. A novel drug-like compound, a resorcinol derivative named RBA4 has been identified. NMR interaction studies demonstrate that RBA4 binds the FGF2/FGFR complex, in agreement with docking prediction. Residue-level NMR perturbations analysis highlights that the mode of action of RBA4 is similar to RA in terms of its ability to target the FGF2/FGFR-D2 complex, inducing perturbations on both proteins and triggering complex dissociation. Biological assays proved that RBA4 inhibited FGF2 proliferative activity at a level comparable to the previously reported natural product, RA. Identification of RBA4 chemical groups involved in direct interactions represents a starting point for further optimization of drug-like extracellular inhibitors with improved activity.

Analysis of the multi-physiological and functional mechanism of wheat alkylresorcinols based on reverse molecular docking and network pharmacology.

Alkylresorcinols (ARs) are phenolic lipids present in the bran part of whole grain wheat and rye, which possess antioxidant, anti-inflammatory, anti-cancer and anti-tumor properties. The physiological activities of ARs have been proven to be diverse; however, the specific molecular mechanisms are still unclear. In this study, reverse virtual screening and network pharmacology were used to explore the potential molecular mechanisms of the physiological function of ARs and their endogenous metabolites. The Metascape database was used for GO enrichment and KEGG pathway analysis. Furthermore, molecular docking was used to investigate the interactions between active compounds and potential targets. The results showed that the bioavailability of most ARs and their endogenous metabolites was 0.55 and 0.56, while the bioavailability of certain endogenous metabolites was only 0.11. Multiplex analysis was used to screen 73 important targets and 4 core targets (namely, HSP90AA1, EP300, HSP90AB1 and ERBB2) out of the 163 initial targets. The important targets involved in the key KEGG pathway were pathways in cancer (hsa05200), lipid and atherosclerosis (hsa05417), Th17 cell differentiation (hsa04659), chemical carcinogenesis-receptor activation (hsa05207), and prostate cancer (hsa05215). The compounds involved in the core targets were AR-C21, AR-C19, AR-C17, 3,5-DHPHTA-S, 3,5-DHPHTA-G, 3,5-DHPPTA, 3,5-DHPPTA-S, 3,5-DHPPTA-G, 3,5-DHPPTA-Gly and 3,5-DHPPA-G. The interaction force between them was mainly related to hydrogen bonds and van der Waals. Overall, the physiological activities of ARs are not only related to their multiple targets, but may also be related to the synergistic effect of their endogenous metabolites.

An efficient differential sensing strategy for phenolic pollutants based on a nanozyme with polyphenol oxidase activity.

To realize the efficient differential sensing of phenolic pollutants in sewage, a novel sensing strategy was successfully developed based on a nanozyme (GMP-Cu) with polyphenol oxidase activity. Phenolic pollutants can be oxidized using GMP-Cu, and the oxidation products reacts subsequently with 4-aminoantipyrine to produce a quinone-imine compound. The absorption spectra of final quinone-imine products that resulted from different phenolic pollutants showed obvious differences, which were due to the interaction difference between GMP-Cu and phenolic pollutants, as well as the different molecular structures of the quinone-imine products from different phenolic pollutants. Based on the difference in the absorption spectra, a novel differential sensing strategy was developed. A genetic algorithm was used to select the characteristic wavelengths at different enzymatic reaction times. Hierarchical cluster analysis and PLS-DA algorithms were utilized for the discriminant sensing of seven representative phenolic pollutants, including hydroquinone, resorcinol, catechol, resorcinol, phenol, p-chlorophenol, and 2,4-dichlorophenol. A scientific wavelength selection algorithm and a recognition algorithm resulted in the successful identification of phenolic pollutants in sewage with a discriminant accuracy of 100%, and differentiation of the phenolic pollutants regardless of their concentration. These results indicated that a sensing strategy can be used as an effective tool for the efficient identification and differentiation of phenolic pollutants in sewage.

Environmental monitoring of trace metal pollutants using cellulosic-paper incorporating color change of azo-chromophore.

An essential requirement for colorimetric paper-sensor is to allow the target analytes (heavy metal ions) to access the chromophore while maintaining strong chromophore immobilization on the porous substrate surface. This work evaluates the selection of sensitive chromophores (dithizone, 1-(2-pyridylazo) 2-naphthol and 4-(2-pyridylazo)-resorcinol) and their immobilization strategies on paper sensors. Dithizone (DTz) are capable of producing a significant color transition at unadjusted pH, observed by UV-Vis absorption spectroscopy and visible recognition. After immobilizing DTz on a paper substrate (cellulose acetate/chitosan substrate), the DTz-paper sensor showed a distinctive color change from blue-green to peach-pink upon reaction with Pb2+ ions, and the color intensity was proportional to the metal concentration. Quantitative analysis using RGB (R:Red; G:Green; B:Blue) plots showed that increasing DTz concentration on the CA/CS paper sensor increases the difference in total color intensity (∆IT) and the difference in red code intensity (∆IR). This is due to the formation of more DTz-Pb2+ complexes on the CA/CS paper substrate. The CA/CS paper strips immobilized with 100 ppm DTz showed practical potential for rapid detection of heavy metal ions. The DTz-CA/CS paper sensor showed significant color change when detecting spiked heavy metals ions (0.1 ppm Pb2+, 2.0 ppm Zn2+, and 0.2 ppm Cu2+) in river water samples that prepared at the maximum permissible limit for industrial effluent in Malaysia.

Sesquiterpene and Sorbicillinoid Glycosides from the Endophytic Fungus Trichoderma longibrachiatum EN-586 Derived from the Marine Red Alga Laurencia obtusa.

An unusual sesquiterpene glycoside trichoacorside A (1) and two novel sorbicillinoid glycosides sorbicillisides A (2) and B (3), together with a known compound sorbicillin (4), were isolated and identified from the culture extract of an endophytic fungus Trichoderma longibrachiatum EN-586, obtained from the marine red alga Laurencia obtusa. Trichoacorside A (1) is the first representative of a glucosamine-coupled acorane-type sesquiterpenoid. Their structures were elucidated based on detailed interpretation of NMR and mass spectroscopic data. The absolute configurations were determined by X-ray crystallographic analysis, chemical derivatization, and DP4+ probability analysis. The antimicrobial activities of compounds 1-4 against several human, aquatic, and plant pathogens were evaluated.

Anion-Based Self-assembly of Resorcin[4]arenes and Pyrogallol[4]arenes.

Spatial sequestration of molecules is a prerequisite for the complexity of biological systems, enabling the occurrence of numerous, often non-compatible chemical reactions and processes in one cell at the same time. Inspired by this compartmentalization concept, chemists design and synthesize artificial nanocontainers (capsules and cages) and use them to mimic the biological complexity and for new applications in recognition, separation, and catalysis. Here, we report the formation of large closed-shell species by interactions of well-known polyphenolic macrocycles with anions. It has been known since many years that C-alkyl resorcin[4]arenes (R4C) and C-alkyl pyrogallol[4]arenes (P4C) narcissistically self-assemble in nonpolar solvents to form hydrogen-bonded capsules. Here, we show a new interaction model that additionally involves anions as interacting partners and leads to even larger capsular species. Diffusion-ordered spectroscopy and titration experiments indicate that the anion-sealed species have a diameter of >26 Å and suggest stoichiometry (M)6(X-)24 and tight ion pairing with cations. This self-assembly is effective in a nonpolar environment (THF and benzene but not in chloroform), however, requires initiation by mechanochemistry (dry milling) in the case of non-compatible solubility. Notably, it is common among various polyphenolic macrocycles (M) having diverse geometries and various conformational lability.

Synthesis and Antimicrobial Activity of δ-Viniferin Analogues and Isosteres.

The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5'-(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 µg/mL).

Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.