Antiviral, virucidal and antioxidant properties of Artemisia annua against SARS-CoV-2.

Natural products are a rich source of bioactive molecules that have potential pharmacotherapeutic applications. In this study, we focused on Artemisia annua (A. annua) and its enriched extracts which were biologically evaluated in vitro as virucidal, antiviral, and antioxidant agents, with a potential application against the COVID-19 infection. The crude extract showed virucidal, antiviral and antioxidant effects in concentrations that did not affect cell viability. Scopoletin, arteannuin B and artemisinic acid (single fractions isolated from A. annua) exerted a considerable virucidal and antiviral effect in vitro starting from a concentration of 50 µg/mL. Data from Surface Plasmon Resonance (SPR) showed that the inhibition of the viral infection was due to the interaction of these compounds with the 3CLpro and Spike proteins of SARS-CoV-2, suggesting that the main interaction of compounds may interfere with the viral pathways during the insertion and the replication process. The present study suggests that natural extract of A. annua and its components could have a key role as antioxidants and antiviral agents and support the fight against SARS-CoV-2 variants and other possible emerging Coronaviruses.

Chemical composition of the essential oil of Cyanus adscendens (Bartl.) Soják and C. orbelicus (Velen.) Soják growing wild in Bulgaria, and PCA analysis of genus Cyanus Mill.

Cyanus Mill. genus, belonging to the Asteraceae family, includes more than 50 taxa, mainly growing in Central and Southern Europe, North Africa, Asia Minor, and the Caucasus. Previous investigations on Cyanus taxa have shown that they are rich source of flavonoids and phenolic compounds but, differently from species of genus Centaurea, almost devoid of sesquiterpene lactones. In the present study, the chemical composition of the essential oils from aerial parts of Cyanus adscendens (CA) and C. orbelicus (CO), collected in Bulgaria, and not previously investigated, was evaluated by GC-MS. The main components of CA were α-bergamotene (31.3%), (Z,Z,Z)-9,12,15-octadecatrien-1-ol (14.5%) and calarenepoxide (11.0%). Caryophyllene oxide (12.0%), together with α-cadinol (10.9%) and spathulenol (8.8%), were recognized as the main constituent of C. orbelicus EO. Furthermore, a complete review on the composition of all essential oils of the Cyanus taxa studied so far has been inserted and cluster analysis (PCA) was carried out.

Efficient 2-Step Enzymatic Cascade for the Bioconversion of Oleuropein into Hydroxytyrosol.

Among the plant bioactive components, oleuropein (OLE) is the most abundant phenolic compound in all parts of olive trees (Olea europaea L.), particularly concentrated in olive leaves. It has been shown to present various remarkable biological actions, such as antimicrobial, antioxidant, anticancer and anti-inflammatory ones. On the other hand, hydroxytyrosol (HT), the main degradation product of OLE, is considered one of the most powerful antioxidant agents, with higher beneficial properties than the OLE parent compound. In this work, oleuropein was efficiently transformed into hydroxytyrosol using a 2-step biotransformation involving a thermo-halophilic ß-glucosidase from Alicyclobacillus herbarius (Ahe), which gave the corresponding aglycone with complete conversion (>99%) and rapid reaction times (30 min), and an acyltransferase from Mycobacterium smegmatis (MsAcT), here employed for the first time for its hydrolytic activity. After cascade completion, hydroxytyrosol was obtained in excellent yield (>99% m.c., 96% isolated yield) in 24 h. Starting from a natural substrate and employing enzymatic approaches, the final hydroxytyrosol can be claimed and commercialized as natural too, thus increasing its market value.

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).

Antioxidant Activity of Citrus Limonoids and Investigation of Their Virucidal Potential against SARS-CoV-2 in Cellular Models.

The COVID-19 pandemic represents an unprecedented global emergency. Despite all efforts, COVID-19 remains a threat to public health, due to the complexity of mass vaccination programs, the lack of effective drugs, and the emergence of new variants. A link has recently been found between the risk of developing a severe COVID-19 infection and a high level of oxidative stress. In this context, we have focused our attention on natural compounds with the aim of finding molecules capable of acting through a dual virucidal-antioxidant mechanism. In particular, we studied the potential of grapefruit seed extracts (GSE) and their main components, belonging to the class of limonoids. Using chemical and biological approaches including isolation and purification of GSE, antioxidant and virucidal assays, we have shown that grapefruit seed constituents, belonging to the class of limonoids, are endowed with remarkable virucidal, antioxidant and mitoprotective activity.

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae.

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.

Inhibitory activity of stilbenes against filamentous fungi.

Stilbenoids (resveratrol and its derivatives) are secondary metabolites produced by plants as defence mechanism to microbial infection. These compounds are known for their anti-inflammatory action and health benefits in preventing a wide range of disorders (e.g. cancer and cardiovascular diseases). However, their antimicrobial properties are less investigated. A series of 8 stilbenoid compounds were synthesized and their antifungal activity against 19 wild strains of filamentous fungi and yeasts (isolated from the environment and food) was tested in vitro. Using an agar diffusion assay, compounds were tested at the concentration of 100 µg/ml on filamentous fungi and yeasts at 104 CFU/ml. The results showed that tested derivatives possess moderate antifungal activity: in particular, monomeric stilbenoids 3'-hydroxy-pterostilbene and piceatannol, and dimeric stilbenoids (±)-trans-δ-viniferin and pallidol were active against mycotoxigenic fungi.

The Essential Oil Compositions of Three Teucrium Taxa Growing Wild in Sicily: HCA and PCA Analyses.

The chemical composition and the qualitative and quantitative variability of the essential oils of three taxa belonging to the Teucrium genus were studied. The investigated taxa, that grow wild in Sicily, were Teucrium flavum L. (section Chamaedrys (Mill.) Scheb.), Teucrium montanum and Teucrium capitatum L. of section Polium (Mill.) Scheb. Essential oils were extracted by hydrodistillation and analyzed by GC-MS. In total, 74 compounds were identified. Sesquiterpene hydrocarbons were found to be the main group for T. flavum (48.3%). T. capitatum consisted essentially of monoterpene hydrocarbons (72.7%), with α-pinene (19.9%), ß-pinene (27.6%) and sylvestrene (16.6%) as the most abundant compounds whereas ledene oxide (12.1%), epiglobulol (13.5%) and longifolenaldehyde (14.5%) were identified as the main constituents among the oxygenated sesquiterpenes (63.5%) of T. montanum. Furthermore, a complete literature review on the composition of the essential oils of all the other accessions of these Teucrium taxa, studied so far, was performed. Hierarchical Cluster Analysis (HCA) and Principal Component Analyses (PCA) were used in order to demonstrate geographical variations in the composition of the essential oils.

Natural and nature-inspired stilbenoids as antiviral agents.

Viruses continue to be a major threat to human health. In the last century, pandemics occurred and resulted in significant mortality and morbidity. Natural products have been largely screened as source of inspiration for new antiviral agents. Within the huge class of plant secondary metabolites, resveratrol-derived stilbenoids present a wide structural diversity and mediate a great number of biological responses relevant for human health. However, whilst the antiviral activity of resveratrol has been extensively studied, little is known about the efficacy of its monomeric and oligomeric derivatives. The purpose of this review is to provide an overview of the achievements in this field, with particular emphasis on the source, chemical structures and the mechanism of action of resveratrol-derived stilbenoids against the most challenging viruses. The collected results highlight the therapeutic versatility of stilbene-containing compounds and provide a prospective insight into their potential development as antiviral agents.

Stilbenoids: A Natural Arsenal against Bacterial Pathogens.

The escalating emergence of resistant bacterial strains is one of the most important threats to human health. With the increasing incidence of multi-drugs infections, there is an urgent need to restock our antibiotic arsenal. Natural products are an invaluable source of inspiration in drug design and development. One of the most widely distributed groups of natural products in the plant kingdom is represented by stilbenoids. Stilbenoids are synthesised by plants as means of protection against pathogens, whereby the potential antimicrobial activity of this class of natural compounds has attracted great interest in the last years. The purpose of this review is to provide an overview of recent achievements in the study of stilbenoids as antimicrobial agents, with particular emphasis on the sources, chemical structures, and the mechanism of action of the most promising natural compounds. Attention has been paid to the main structure modifications on the stilbenoid core that have expanded the antimicrobial activity with respect to the parent natural compounds, opening the possibility of their further development. The collected results highlight the therapeutic versatility of natural and synthetic resveratrol derivatives and provide a prospective insight into their potential development as antimicrobial agents.

Solid state 13C-NMR methodology for the cellulose composition studies of the shells of Prunus dulcis and their derived cellulosic materials.

Lignocellulosic fibers and microcellulose have been obtained by simple alkaline treatment from softwood almond shells. In particular, the Prunus dulcis Miller (D.A.) Webb. was considered as a agro industrial waste largely available in southern Italy. The materials before and after purification have been characterized by 13C CPMAS NMR spectroscopy methodology. A proper data analysis provided the relative composition of lignin and holocellulose at each purification step and the results were compared with thermogravimetric analysis and FT-IR. To value the possibility of using this material in a circular economy framework, the fibrous cellulosic material was used to manufacture a handmade cardboard. The tensile performances on the prepared cardboard proved its suitability for packaging purposes as a sustainable material. These fibers along with the obtained microcellulose can represent a new use for the almond shells that are mainly used as firewood.

Structural Requirements of Benzofuran Derivatives Dehydro-δ- and Dehydro-ε-Viniferin for Antimicrobial Activity Against the Foodborne Pathogen Listeria monocytogenes.

In a recent study, we investigated the antimicrobial activity of a collection of resveratrol-derived monomers and dimers against a series of foodborne pathogens. Out of the tested molecules, dehydro-δ-viniferin and dehydro-ε-viniferin emerged as the most promising derivatives. To define the structural elements essential to the antimicrobial activity against the foodborne pathogen L. monocytogenes Scott A as a model Gram-positive microorganism, the synthesis of a series of simplified benzofuran-containing derivatives was carried out. The systematic removal of the aromatic moieties of the parent molecules allowed a deeper insight into the most relevant structural features affecting the activity. While the overall structure of compound 1 could not be altered without a substantial loss of antimicrobial activity, the structural simplification of compound 2 (minimal inhibitory concentration (MIC) 16 µg/mL, minimal bactericidal concentration (MBC) >512 µg/mL) led to the analogue 7 with increased activity (MIC 8 µg/mL, MBC 64 µg/mL).

Synthesis of Rosmarinic Acid Amides as Antioxidative and Hypoglycemic Agents.

Type 2 diabetes mellitus (T2DM) is an important metabolic disorder for which there is an urgent need for new antidiabetic drugs. α-Glucosidase inhibition is an established protocol for T2DM therapy. Because hyperglycemia causes oxidative tissue damage, the development of agents with both α-glucosidase inhibition and antioxidant activity from natural or natural-derived polyphenols such derivatives of rosmarinic acid (RA) represents an attractive therapeutic option. We report a study on amides 1-10 derived from RA and their evaluation for yeast α-glucosidase inhibition and antioxidant activity (DPPH and ORAC tests). All amides showed higher inhibitory activity than that of RA, were by far more potent than the antidiabetic drug acarbose, and proved to be effective antioxidants. A molecular docking study displayed significant binding interactions of RA amides with the active site of α-glucosidase. This in silico optimization study led to the design and synthesis of amides 9 (IC50 = 42.3 µM) and 10 (IC50 = 35.2 µM), showing the most potent α-glucosidase inhibition and good antioxidative properties. A kinetic study showed that 10 acts as a mixed type inhibitor.

Chemical composition of the essential oils of Centaurea tomentella Hand.-Mazz. and C. haussknechtii Boiss. (Asteraceae) collected wild in Turkey and their activity on microorganisms affecting historical art craft.

In the present study the chemical composition of the essential oils from aerial parts of Centaurea tomentella Hand.-Mazz. and C. haussknechtii Boiss. collected in Turkey was evaluated by GC and GC-MS. The main components of C. tomentella L. were hexadecanoic acid (19.7%), caryophyllene oxide (6.6%) and spathulenol (4.8%) whereas C. haussknechtii was rich in hexadecanoic acid (26.2%), (Z,Z)-9,12-octadecadienoic acid (19.3%), heptacosane (5.3%) and nonacosane (5.1%). Antibacterial and antifungal activities against some microorganisms infesting historical art craft, were also determined.

Investigating the Antiproliferative and Antioxidant Properties of Pancratium maritimum L. (Amaryllidaceae) Stems, Flowers, Bulbs, and Fruits Extracts.

Pancratium maritimum stems, flowers, bulbs, and fruits extracts were investigated for their antiproliferative and antioxidant properties. Total phenols and total flavonoids were also determined. The in vitro antiproliferative activity was tested against seven cancer cell lines such as C32, HeLa, MDA-MB-231, PC3, A549, MCF-7, and LNCaP by using SRB assay. Interesting results were obtained with stems ethanol extract (ET1) against C32 cells (IC50 of 27.1 µg/mL) and fruits aqueous extract (AQ) against MCF-7 cell line (IC50 of 36.5 µg/mL). To define the antioxidant activity, four tests such as DPPH, ABTS FRAP, and ß-carotene bleaching tests were used. The most promising ABTS scavenging capacity was observed with fruits ethanol extract (ET1) that showed an IC50 value of 6.9 µg/mL. According to the correlation results, the phenols and flavonoids content could provide a fundamental contribution to the antioxidant and antiproliferative activity of P. maritimum extracts.