In light of pressing global nutritional needs, the valorization of agri-food waste constitutes a vital strategy for enhancing human health and nutrition, while simultaneously supporting planetary health. This integrated approach is increasingly indispensable within sustainable and equitable food systems. Recently, a sustainability-driven focus has shifted attention toward the valorization of the agri-food by-products as rich sources of bioactive compounds useful in preventing or treating chronic diseases. Agri-food by-products, often regarded as waste, actually hold great potential as they are rich in bioactive components, dietary fiber, and other beneficial nutrients from which innovative food ingredients, functional foods, and even therapeutic products are developed. This review aims to provide a comprehensive analysis of the current advances in recovering and applying such compounds from agri-food waste, with a particular focus on their roles in human health, sustainable packaging, and circular economy strategies. Methods: This review critically synthesizes recent scientific literature on the extraction, characterization, and utilization of bioactive molecules from agri-food by-products. After careful analysis of the PubMed and Scopus databases, only English-language articles from the last 10 years were included in the final narrative review. The analysis also encompasses applications in the nutraceutical, pharmaceutical, and food packaging sectors. Results: Emerging technologies have enabled the efficient and eco-friendly recovery of compounds such as polyphenols, carotenoids, and dietary fibers that demonstrate antioxidant, antimicrobial, and anti-inflammatory properties. These bioactive compounds support the development of functional foods and biodegradable packaging materials. Furthermore, these valorization strategies align with global health trends by promoting dietary supplements that counteract the effects of the Western diet and chronic diseases. Conclusions: Valorization of agri-food by-products offers a promising path toward sustainable development by reducing waste, enhancing public health, and driving innovation. This strategy not only minimizes waste and supports sustainability, but also promotes a more nutritious and resilient food system.

In the quest for selective G-quadruplex (G4)-targeting chemotypes, natural compounds have been thus far poorly explored, though representing appealing candidates due to the high structural diversity of their scaffolds. In this regard, a unique high diversity in-house library composed of ca. one thousand individual natural products was investigated. The combination of molecular docking-based virtual screening and the G4-CPG experimental screening assay proved to be useful to quickly and effectively identify—out of many natural compounds—five hit binders of telomeric and oncogenic G4s, i.e., Bulbocapnine, Chelidonine, Ibogaine, Rotenone and Vomicine. Biophysical studies unambiguously demonstrated the selective interaction of these compounds with G4s compared to duplex DNA. The rationale behind the G4 selective recognition was suggested by molecular dynamics simulations. Indeed, the selected ligands proved to specifically interact with G4 structures due to peculiar interaction patterns, while they were unable to firmly bind to a DNA duplex. From biological assays, Chelidonine and Rotenone emerged as the most active compounds of the series against cancer cells, also showing good selectivity over normal cells. Notably, the anticancer activity correlated well with the ability of the two compounds to target telomeric G4s.

The plants of the Moraceae family are producers of a great variety of polyphenolic natural products. Among these, the Diels–Alder type adducts (DAAs) are endowed with a unique cyclohexene scaffold, since they are biosynthesized from [4+2] cycloaddition of different polyphenolic precursors such as chalcones and dehydroprenyl polyphenols. To date, more than 150 DAAs have been isolated and characterized from Moraceous and related plants. The main source of DAAs is the mulberry root bark, also known as “Sang-Bai-Pi” in Traditional Chinese Medicine, but they have also been isolated from root bark, stem barks, roots, stems or twigs, leaves, and callus cultures of Moraceous and other related plants. Since 1980, many biological activities of DAAs have been identified, including anti-HIV, antimicrobial, anti-inflammatory, and anticancer ones. For these reasons, natural DAAs have been intensively investigated, and a lot of efforts have been made to study their biosynthesis and to establish practical synthetic access. In this review, we summarized all the updated knowledge on biosynthesis, chemoenzymatic synthesis, racemic and enantioselective total synthesis, and biological activity of natural DAAs from Moraceous and related plants.

In today’s post-antibiotic era, the search for new antimicrobial compounds is of major importance and nature represents one of the primary sources of bioactive molecules. In this work, through a cheminformatics approach, we clustered an in-house library of natural products and their derivatives based on a combination of fingerprints and substructure search. We identified the prenylated emodine-type anthranoid ferruginin A as a novel antimicrobial compound. We tested its ability to inhibit and kill a panel of Gram-positive and Gram-negative bacteria, and compared its activity with that of two analogues, vismione B and ferruanthrone. Furthermore, the capability of these three anthranoids to disrupt staphylococcal biofilm was investigated, as well as their effect on the viability of human keratinocytes. Ferruginin A showed a potent activity against both the planktonic and biofilm forms of Gram-positive bacteria (i.e., Staphylococcus aureus and S. epidermidis) and had the best therapeutic index compared to vismione B and ferruanthrone. In conclusion, ferruginin A represents a promising scaffold for the further development of valuable antimicrobial agents.

The gold-catalyzed cyclization of 2,2-bis(3-arylprop-2-yn1-yl)malonic acid has been proposed as an efficient approach to substituted 3,8-dibenzyl-2,7-dioxaspiro[4.4]nonane-1,6-diones. The reaction proceeds smoothly in mild reaction conditions to give the desired products in quantitative yields in the presence of variously substituted starting materials. In addition, the synthesis of γ-arylidene spirobislactone bearing different substituents on the two aromatic rings has been achieved. This kind of compound could be of great interest in pharmaceutical science given the widespread presence of this scaffold in bioactive natural and synthetic products.

Zn complexes of naringenin and its chalcone were analyzed by ion spectroscopy, showing similar IR spectra coherent with an isomerization equilibrium. Gas-phase activation causes oxidative Zn ⁰ loss yielding two isomers via a Zn-promoted phenol shift.