Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors

The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases. However, the development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. We previously reported 7H-furo[3,2-g]chromen-7-one (psoralen)-based compounds with an oxathiazolone warhead as selective inhibitors of the chymotrypsin-like (β5i) subunit of immunoproteasome. Here, we describe the influence of the electrophilic warhead variations at position 3 of the psoralen core on the inhibitory potencies. Despite mapping the chemical space with different warheads, all compounds showed decreased inhibition of the β5i subunit of immunoproteasome in comparison to the parent oxathiazolone-based compound. Although suboptimal, these results provide crucial information about structure–activity relationships that will serve as guidance for the further design of (immuno)proteasome inhibitors.     

Identification of Organic Volatile Markers Associated with Aroma during Maturation of Strawberry Fruits

In the present study, organic volatile markers of three strawberry varieties (Albion, Festival and Frontera) during the maturation process were investigated. Forty metabolites associated with aroma in fresh strawberries were monitored during seven stages of maturation using gas chromatography–mass spectrometry (GC-MS) equipped with headspace-solid phase microextraction (HS-SPME). The data were evaluated using multivariate analysis to observe correlations between the organic volatile compound profile and the seven phenological stages of maturation for each strawberry variety. The dynamic levels of butanoic acid methyl ester, hexanoic acid methyl ester, octylcyclohexane, cyclohexane,1,1,2-trimethyl, linalool, tetradecane, and α-muurolene underwent distinctive changes in concentration during the maturation process. The multivariate analysis also allowed the identification of these compounds as possible volatile markers to measure the maturation of strawberry fruits in all three varieties. These findings highlight the importance of the timing of harvest and maturation stage in each variety to preserve or improve the desirable aromatic characteristics of strawberry fruits.     

Bioactive Phenolic Compounds from Primula veris L.: Influence of the Extraction Conditions and Purification

Our experiments may help to answer the question of whether cowslip (Primula veris L.) is a rich source of bioactive substances that can be obtained by efficient extraction with potential use as a food additive. A hypothesis assumed that the type of solvent used for plant extraction and the individual morphological parts of Primula veris L. used for the preparation of herbal extracts will have key impacts on the efficiency of the extraction of bioactive compounds, and thus, the health-promoting quality of plant concentrates produced. Most analysis of such polyphenolic compound contents in extracts from Primula veris L. has been performed by using chromatography methods such as ultra-performance reverse-phase liquid chromatography (UPLC−PDA−MS/MS). Experiments demonstrated that the most effective extraction agent for fresh study material was water at 100 °C, whereas for dried material it was 70% ethanol. The richest sources of polyphenolic compounds were found in cowslip primrose flowers and leaves. The aqueous and ethanol extracts from Primula veris L. were characterized by a quantitatively rich profile of polyphenolic substances, and a high antioxidative potential. Selective extraction with the use of mild conditions and neutral solvents is the first step to obtaining preparations from cowslip primrose with a high content of bioactive substances.     

Medicinal Properties and Bioactive Compounds from Wild Mushrooms Native to North America

Mushrooms, the fruiting bodies of fungi, are known for a long time in different cultures around the world to possess medicinal properties and are used to treat various human diseases. Mushrooms that are parts of traditional medicine in Asia had been extensively studied and this has led to identification of their bioactive ingredients. North America, while home to one of the world’s largest and diverse ecological systems, has not subjected its natural resources especially its diverse array of mushroom species for bioprospecting purposes: Are mushrooms native to North America a good source for drug discovery? In this review, we compile all the published studies up to September 2020 on the bioprospecting of North American mushrooms. Out of the 79 species that have been investigated for medicinal properties, 48 species (60%) have bioactivities that have not been previously reported. For a mere 16 selected species, 17 new bioactive compounds (10 small molecules, six polysaccharides and one protein) have already been isolated. The results from our literature search suggest that mushrooms native to North America are indeed a good source for drug discovery.     

Probiotic Yoghurts with Sea Buckthorn,Elderberry, and Sloe Fruit Purees

Elderberries, sea buckthorn, and sloe berries are fruits of wild-grown bushes, valued in folk medicine for their health-promoting properties but still rarely applied in food. The aim of the present study was to produce probiotic yoghurts with a 10% addition of sweetened purees prepared from elderberries (EPY), sea buckthorn (SBPY), and sloe berries (SPY) and to assess their chemical composition, acidity, content of polyphenols and anthocyanins, ferric reducing antioxidant power (FRAP) and antiradical power (ARP), level of starter microbiota, concentration of acetaldehyde and diacetyl, syneresis, instrumentally measured color and texture parameters, and sensory acceptance. The results were compared to those obtained for plain probiotic yoghurt (PPY) and the changes tracked during 1 month of cold storage at 2 week intervals. The addition of elderberry and sloe berries significantly increased the antioxidant capacity of probiotic yoghurts, probably due to a high content of polyphenols, especially anthocyanins. However, anthocyanins were more stable in the EPY when compared to the SPY. All yoghurt treatments were characterized by good sensory quality and viability of starter microorganisms, including probiotic strains during cold storage. Elderberries promoted the evolution of diacetyl in yoghurts during storage and, together with sloe berries, produced increased syneresis and the greatest changes in color profile compared to PPY.     

Statistics of the Popularity of Chemical Compounds in Relation to the Non-Target Analysis

The idea of popularity/abundance of chemical compounds is widely used in non-target chemical analysis involving environmental studies. To have a clear quantitative basis for this idea, frequency distributions of chemical compounds over indicators of their popularity/abundance are obtained and discussed. Popularity indicators are the number of information sources, the number of chemical vendors, counts of data records, and other variables assessed from two large databases, namely ChemSpider and PubChem. Distributions are approximated by power functions, special cases of Zipf distributions, which are characteristic of the results of human/social activity. Relatively small group of the most popular compounds has been denoted, conventionally accounting for a few percent (several million) of compounds. These compounds are most often explored in scientific research and are practically used. Accordingly, popular compounds have been taken into account as first analyte candidates for identification in non-target analysis.     

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC₅₀ (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC₅₀ (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots’ crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.     

Comparative Studies of Selected Criteria Enabling Optimization of the Extraction of Polar Biologically Active Compounds from Alfalfa with Supercritical Carbon Dioxide

The aim of this research was to provide crucial and useful data about the selection of the optimization criteria of supercritical carbon dioxide extraction of alfalfa at a quarter-technical plant. The correlation between more general output, including total phenolics and flavonoids content, and a more specified composition of polar constituents was extensively studied. In all alfalfa extracts, polar bioactive constituents were analyzed by both spectrometric (general output) and chromatographic (detailed output) analyses. Eight specific phenolic acids and nine flavonoids were determined. The most dominant were salicylic acid (221.41 µg g⁻¹), ferulic acid (119.73 µg g⁻¹), quercetin (2.23 µg g⁻¹), and apigenin (2.60 µg g⁻¹). For all seventeen analyzed compounds, response surface methodology and analysis of variance were used to provide the optimal conditions of supercritical fluid extraction for each individual constituent. The obtained data have shown that eight of those compounds have a similar range of optimal process parameters, being significantly analogous for optimization based on total flavonoid content.     

Modern Synthetic Strategies with Organoselenium Reagents: A Focus on Vinyl Selenones

In recent years, vinyl selenones were rediscovered as useful building blocks for new synthetic transformations. This review will highlight these advances in the field of multiple-bond-forming reactions, one-pot synthesis of carbo- and heterocycles, enantioselective construction of densely functionalized molecules, and total synthesis of natural products.     

Effect of Filtrated Osmotic Solution Based on Concentrated Chokeberry Juice and Mint Extract on the Drying Kinetics,Energy Consumption and Physicochemical Properties of Dried Apples

Background: Filtration of osmotic solution affects selective penetration during osmotic dehydration (OD), and after drying is finished, this can influence the chemical composition of the material, which is also modified by OD. Methods: Osmotic dehydration was carried out in filtrated and non-filtrated concentrated chokeberry juice with the addition of mint infusion. Then, this underwent convective drying, vacuum-microwave drying and combined convective pre-drying, followed by vacuum-microwave finishing drying. Drying kinetics were presented and mathematical models were selected. The specific energy consumption for each drying method was calculated and the energy efficiency was determined. Results and Discussion: The study revealed that filtration of osmotic solution did not have significant effect on drying kinetics; however, it affected selective penetration during OD. The highest specific energy consumption was obtained for the samples treated by convective drying (CD) (around 170 kJ·g⁻¹ fresh weight (fw)) and the lowest for the samples treated by vacuum-microwave drying (VMD) (around 30 kJ·g⁻¹ fw), which is due to the differences in the time of drying and when these methods are applied. Conclusions: Filtration of the osmotic solution can be used to obtain the desired material after drying and the VMD method is the most appropriate considering both phenolic acid content and the energy aspect of drying.