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.

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, resveratrolderived 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.

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 (IC 50 = 42.3 μM) and 10 (IC 50 = 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.

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.

Lignocellulosic fibres and microcrystalline cellulose have been obtained by simple alkaline treatment from softwood almond (Prunus dulcis Miller (D.A.) Webb.) shells constituting a large agro industrial waste in our territory. The materials have been characterized for the relative composition of lignin and holocellulose, applying a 13C CPMAS NMR spectroscopy methodology. The fibrous material allowed the manufacture of a handmade cardboard obtaining an ecological material suitable for packaging purposes. These fibers along with the obtained microcrystalline cellulose can represent a new fate for the almond shells that are mainly used as firewood.

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%), β-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.

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.

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).