Showing papers by "Artur M. S. Silva published in 2020"

The Antioxidant Activity of Prenylflavonoids.

Abstract: Prenylated flavonoids combine the flavonoid moiety and the lipophilic prenyl side-chain. A great number of derivatives belonging to the class of chalcones, flavones, flavanones, isoflavones and other complex structures possessing different prenylation patterns have been studied in the past two decades for their potential as antioxidant agents. In this review, current knowledge on the natural occurrence and structural characteristics of both natural and synthetic derivatives was compiled. An exhaustive survey on the methods used to evaluate the antioxidant potential of these prenylflavonoids and the main results obtained were also presented and discussed. Whenever possible, structure-activity relationships were explored.

Iron: A Worthy Contender in Metal Carbene Chemistry

Abstract: Carbene transfer reactions hold a pivotal role in organic synthesis, allowing the prompt construction of complex molecules from accessible reagents. Iron complexes emerged as promising catalysts fo...

Microwave-Assisted Extraction of Phlorotannins from Fucus vesiculosus.

Abstract: Microwave-assisted extraction (MAE) was carried out to maximize the extraction of phlorotannins from Fucus vesiculosus using a hydroethanolic mixture as a solvent, as an alternative to the conventional method with a hydroacetonic mixture. Optimal MAE conditions were set as ethanol concentration of 57% (v/v), temperature of 75 °C, and time of 5 min, which allowed a similar recovery of phlorotannins from the macroalgae compared to the conventional extraction. While the phlorotannins richness of the conventional extract was slightly superior to that of MAE (11.1 ± 1.3 vs. 9.8 ± 1.8 mg PGE/g DWextract), both extracts presented identical phlorotannins constituents, which included, among others, tetrafucol, pentafucol, hexafucol, and heptafucol structures. In addition, MAE showed a moderate capacity to scavenge ABTS•+ (IC50 of 96.0 ± 3.4 µg/mL) and to inhibit the activity of xanthine oxidase (IC50 of 23.1 ± 3.4 µg/mL) and a superior ability to control the activity of the key metabolic enzyme α-glucosidase compared to the pharmaceutical drug acarbose.

Phlorotannins from Fucus vesiculosus: Modulation of Inflammatory Response by Blocking NF-κB Signaling Pathway.

Abstract: Due to their large spectrum of bioactive properties, much attention has recently been drawn to phlorotannins—i.e., phenolic compounds characteristic from brown macroalgae. This study aimed to evaluate the antioxidant and anti-inflammatory properties of F. vesiculosus phlorotannin extracts and purified fractions. Overall, the crude extract and its ethyl acetate fraction (EtOAc) showed good radical scavenging activity, particularly towards nitric oxide (NO•). Subsequent subfractions of EtOAc (F1 to F9) with different molecular weights were then shown to inhibit lipopolysaccharide-induced NO• production in macrophages, with stronger effects being observed for fractions of lower MWs. Of the three intracellular markers analyzed, inducible NO• synthase showed the highest sensitivity to almost all the phlorotannin-rich samples, followed by interleukin 1β and cyclooxygenase 2, which was only inhibited by F2. Furthermore, this subfraction inhibited the phosphorylation and degradation of inhibitory protein κBα, thus preventing the activation of NF-κB and blocking the inflammatory cascade at the transcriptional level. This sample was characterized by the presence of a major compound with a deprotonated molecular ion at m/z 507 with a fragmentation pattern coherent with that of a phlorotannin derivative. Overall, this work unveiled some of the mechanistic aspects behind the anti-inflammatory capacity of phlorotannins from F. vesiculosus, endorsing its use as a possible natural source of anti-inflammatory compounds.

Inclusion Complex of Resveratrol with γ-Cyclodextrin as a Functional Ingredient for Lemon Juices.

Abstract: Microencapsulated resveratrol (RSV) is a pertinent ingredient in functional foods to be used in the prevention and management of cardiovascular diseases. Gamma-cyclodextrin (γ-CD) was evaluated for its RSV inclusion ability. Inclusion procedures comprised mixing equal concentration of an aqueous solution of γ-CD with an ethanol solution of RSV and freeze-drying to obtain a solid material. Solid-state characterization by vibrational spectroscopy, thermogravimetry, and powder X-ray diffraction (PXRD) confirmed the formation of the γ-CD·RSV complex in a ratio of 1:1. PXRD suggested that cyclodextrin molecules in the complex are stacked in infinite channels holding the RSV inside, with a wide inter-channel space where 14 water molecules are retained. Fresh lemon juices supplemented with 0.625 mg/mL of RSV in its free (RSV-juice) or complexed (γ-CD·RSV-juice) form were stored along 28 days under dark and room temperature or at 4 °C. Initially, the RSV level in γ-CD·RSV-juice was about nine times higher than in RSV-juice (43.1% and 4.8%, respectively), suggesting that the RSV complexation promoted its solubility in the lemon juice, a fact that was still noticed after 28 days of storage. Moreover, regardless the fact that the antioxidant capacity was similar among the juices, the loss of antiradical ABTS•+ capacity in γ-CD·RSV-juice was reduced compared to that of the RSV-juice. Overall, this study allowed concluding that γ-CD can serve as a carrier of RSV, promoting its solubility and eventually protecting its antioxidant stability in lemon juices for at least 28 days.

Application of Hydroxytyrosol in the Functional Foods Field: From Ingredient to Dietary Supplements.

Abstract: Hydroxytyrosol (HT) is an amphipathic functional phenol found in the olive tree, both in its leaves and fruits, in free or bound forms, as well as in olive oil and by-products of olive oil manufacture. The European Food Safety Authority recommends regular consumption of HT due to its several beneficial effects on human health, which are closely associated to its antioxidant activity. These reasons make HT an excellent candidate for application as a functional ingredient in the design of novel food products. Patents already exist for methodologies of extraction, purification, and application of HT in supplements and food products. The present review discusses the impact of HT incorporation on food properties and its effects on consumers, based on relevant data related to the use of HT as a functional ingredient, both as a pure compound or in the form of HT-rich extracts, in various food products, namely in edible oils, beverages, bakery products, as well animal-based foods such as meat, fishery and dairy products.

A 1000-year-old mystery solved: Unlocking the molecular structure for the medieval blue from Chrozophora tinctoria, also known as folium

Abstract: The molecular structure of the medieval watercolor known as folium has finally been solved in the 21st century. The interdisciplinary approach taken was the key to producing extracts that had been prepared following medieval instructions, and shows the blue/purple chromophore as the major dye in Chrozophora tinctoria fruits (shell). A multi-analytical characterization of its structure was made using HPLC-DAD-MS, GC-MS, NMR (1H, 13C, COSY, HSQC, HMBC, INADEQUATE), and computational studies. The results demonstrate that the blue compound corresponds to 6'-hydroxy-4,4'-dimethoxy-1,1'-dimethyl-5'-{[3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-[3,3'-bipyridine]-2,2',5,6(1H,1'H)-tetraone, a hermidin derivative, which we named chrozophoridin. Experimental data and computational modeling studies show that this mono-glycosylated dimer is represented by two stable isomers (atropisomers). This is an indispensable piece of knowledge for the characterization of this medieval dye in works of art such as medieval manuscript illuminations and for testing its stability and contributes to the preservation of our cultural heritage.

Characterization and Cytotoxicity Assessment of the Lipophilic Fractions of Different Morphological Parts of Acacia dealbata.

Abstract: Acacia dealbata biomass, either from forest exploitation or from the management of invasive species, can be a strategic topic, namely as a source of high-value compounds. In this sense, the present study aimed at the detailed characterization of the lipophilic components of different morphological parts of A. dealbata and the evaluation of their cytotoxicity in cells representative of different mammals’ tissues. The chemical composition of lipophilic extracts from A. dealbata bark, wood and leaves was evaluated using gas chromatography-mass spectrometry (GC–MS). Terpenic compounds (representing 50.2%–68.4% of the total bark and leaves extracts, respectively) and sterols (60.5% of the total wood extract) were the main components of these extracts. Other constituents, such as fatty acids, long-chain aliphatic alcohols, monoglycerides, and aromatic compounds were also detected in the studied extracts. All the extracts showed low or no cytotoxicity in the different cells tested, demonstrating their safety profile and highlighting their potential to be used in nutraceutical or pharmaceutical applications. This study is therefore an important contribution to the valorization of A. dealbata, demonstrating the potential of this species as a source of high value lipophilic compounds.

Flavonoid Profile of the Genista tridentata L., a Species Used Traditionally to Treat Inflammatory Processes

Abstract: Ethnopharmacological surveys on Portuguese flora reveal that Genista tridentata L. is a shrub used in traditional medicine for the treatment of various inflammation-related health problems, although scientific support of its benefits is still necessary. In order to establish the anti-inflammatory potential of G. tridentata and support its traditional use, ethanolic extracts of three sections of the plant (root, stem, and leaves) were subjected to in vitro evaluation of anti-inflammatory activity using lipopolysaccharide (LPS)-stimulates macrophages as an inflammation model. Simultaneously, we also aimed to establish the extracts’ flavonoids profile. The ethanolic extracts, obtained by Soxhlet extraction, profile of the three sections confirmed their richness in flavonoids, being three prenylated flavonoids isolated and characterized in the root, including a new natural compound, the 3-methoxymundulin. The extracts from the three plant sections showed strong antioxidant activity at the cellular level and significantly inhibit the LPS-triggered NO production by downregulating Nos2 gene transcription and consequently iNOS expression. Additionally, root and stem extracts also decreased the LPS-induced transcription of the pro-inflammatory genes Il1b, Il6, and Ptgs2. Thus, the results support the anti-inflammatory properties attributed to G. tridentate preparations. Relevantly, the roots of the shrub, plant part not used, is an unexplored source of compounds with pharmacological and nutraceutical value.

Styrylpyrazoles: Properties, Synthesis and Transformations.

Abstract: The pyrazole nucleus and its reduced forms, pyrazolines and pyrazolidine, are privileged scaffolds in medicinal chemistry due to their remarkable biological activities. A huge number of pyrazole derivatives have been studied and reported over time. This review article gives an overview of pyrazole derivatives that contain a styryl (2-arylvinyl) group linked in different positions of the pyrazole backbone. Although there are studies on the synthesis of styrylpyrazoles dating back to the 1970s and even earlier, this type of compound has rarely been studied. This timely review intends to summarize the properties, biological activity, methods of synthesis and transformation of styrylpyrazoles; thus, highlighting the interest and huge potential for application of this kind of compound.

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET).

Abstract: The need for increasingly personalized medicine solutions (precision medicine) and quality medical treatments, has led to a growing demand and research for image-guided therapeutic solutions. Positron emission tomography (PET) is a powerful imaging technique that can be established using complementary imaging systems and selective imaging agents-chemical probes or radiotracers-which are drugs labeled with a radionuclide, also called radiopharmaceuticals. PET has two complementary purposes: selective imaging for diagnosis and monitoring of disease progression and response to treatment. The development of selective imaging agents is a growing research area, with a high number of diverse drugs, labeled with different radionuclides, being reported nowadays. This review article is focused on the use of pyrazoles as suitable scaffolds for the development of 18F-labeled radiotracers for PET imaging. A brief introduction to PET and pyrazoles, as key scaffolds in medicinal chemistry, is presented, followed by a description of the most important [18F]pyrazole-derived radiotracers (PET tracers) that have been developed in the last 20 years for selective PET imaging, grouped according to their specific targets.

Structural Features and Pro-Inflammatory Effects of Water-Soluble Organic Matter in Inhalable Fine Urban Air Particles.

Abstract: The impact of inhalable fine particulate matter (PM2.5, aerodynamic diameter <2.5 μm) on public health is of great concern worldwide. Knowledge on their harmful effects are mainly due to studies ca...

Structural Specificity of Flavonoids in the Inhibition of Human Fructose 1,6-Bisphosphatase

Abstract: Liver fructose 1,6-bisphosphatase (FBPase) is a recognized regulatory enzyme of the gluconeogenesis pathway, which has emerged as a valid target to control gluconeogenesis-mediated overproduction o...

UHPLC-DAD-ESI-MSn profiling variability of the phenolic constituents of Artemisia campestris L. populations growing in Algeria

Abstract: Due to its health-promoting properties, Artemisia campestris L. is an important crop widely used in the south Mediterranean basin as a food spice, and also in folk medicine. In this study, crude methanolic fraction was fractionated using two different solvents (ethyl-acetate AC and dichloromethane DCM). 19 individuals representing two different subspecies of A. campestris were investigated. A total of 86 compounds were identified. Several major and minor compounds were tentatively identified for the first time for this plant subspecies. The AC and DCM fractions exhibited different profiles compositions. Furthermore, both fractions presented a large variability of the percentage of their components. The AC fraction was rich in hydroxycinnamic acids and flavonoids aglycones. Major compounds for this fraction were 3,5-dicaffeoylquinic (7.0–50.03%), 4,5-dicaffeoylquinic acid derivative (0.11–11.15%) and luteolin (0–14.2%). Alternatively, for DCM fraction, it was mainly made up by flavonols and flavones classes'. The major identified components were 3-O-methylquercetin (8.7–19.1%), casticin III (0.0–9.3%), cirsiliol (3.89–14.0), eupatorin-5-methylether (3.4–11.5%), eupatorin (4.04–12.00%), eupafolin (1.4–9.55%) and 5,8,4′-trihydroxy-7-methoxyflavone (0.0–15.41%). Cluster analysis showed the presence two mains clusters and were depending on the solvent used. The chemical variation among the populations should lead to the selection of plants with high potential in order to use them in health care and food industry.

Ionic Liquids and Ohmic Heating in Combination for Pd-catalyzed Cross-coupling Reactions: Sustainable Synthesis of Flavonoids

Abstract: In order to meet the increasing demand for environmentally benign chemical processes, we developed a Suzuki-Miyaura reaction protocol based on the combination of ohmic heating (ΩH) and supported ionic liquid phase catalysis (SILPC) in aqueous media. This methodology was applied to the synthesis of a series of flavonoid derivatives, including isoflavones, styrylisoflavones, and diarylalkenylisoflavones.

Genista tridentata L.: A Rich Source of Flavonoids with Anti-inflammatory Activity.

Abstract: Background: Genista tridentata L. is an endemic species from the Iberian Peninsula used in Portuguese traditional medicine to treat inflammation-related diseases; this and other health-promoting effects are usually associated with the flavonoids produced by this species. In fact, anti-inflammatory properties were established for several of these flavonoid derivatives. Methods: A careful survey of the reported data, using mainly the Scopus database and Genista tridentata and Pterospartum tridentatum as keywords, was done. We have examined the papers involving the plant and those about the most relevant flavonoids anti-inflammatory activity. Results: The literature survey demonstrates that species are used to treat several health problems such as antihyperglycemia, hypertension, and inflammatory episodes. It was also possible to establish its richness in flavonoid derivatives, from which several are potential anti-inflammatory agents. Conclusions: From our described and discussed analysis, it can be concluded that Genista tridentata is an excellent source of bioactive flavonoids. Moreover, its traditional use to treat inflammation episodes may be due to its flavonoid content, from which genistein, biochanin A, rutin, and daidzein can be emphasized.

1,2,4-Triphenylpyrroles: Synthesis, Structure and Luminescence Properties

Abstract: Pyrroles are widely found in natural products and play an important role in biological processes. Certain pyrrole derivatives are fluorescent and may be used as molecular probes or biomarkers in the diagnosis of diseases, such as Alzheimer’s or Parkinson’s. Herein is reported the synthesis of five new pyrrole derivatives bearing phenyl rings on positions 1, 2, and 4, with electron-donating groups at the periphery. The introduction of more or stronger electron-donating groups red-shifts and increases the efficiency of the fluorescence emission.

Structural Characterization of Dissolved Organic Matter in Permafrost Peatland Lakes

Abstract: Thermokarst lakes result from the thawing of ice-rich permafrost and are widespread across northern landscapes. These waters are strong emitters of methane, especially in permafrost peatland regions, where they are stained black by high concentrations of dissolved organic matter (DOM). In the present study, we aimed to structurally characterize the DOM from a set of peatland thermokarst lakes that are known to be intense sites of microbial decomposition and methane emission. Samples were collected at different depths from three thermokarst lakes in the Sasapimakwananisikw (SAS) River valley near the eastern Hudson Bay community of Kuujjuarapik–Whapmagoostui (Nunavik, Canada). Samples were analyzed by spectrofluorometry, Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and elemental analysis. Fluorescence analyses indicated considerable amounts of autochthonous DOM in the surface waters of one of SAS 1A, indicating a strong bioavailability of labile DOM, and consequently a greater methanogenic potential. The three lakes differed in their chemical composition and diversity, suggesting various DOM transformations phenomena. The usefulness of complementary analytical approaches to characterize the complex mixture of DOM in permafrost peatland waters cannot be overlooked, representing a first step towards greater comprehension of the organic geochemical properties of these permafrost-derived systems.