Sulla (Hedysarum coronarium L.) is a biennal forage legume originated from the Mediterranean basin and used for animal feeding due to its high forage quality and palatability. Several species of Hedysarum have been considered for their nutritional, pharmaceutical, and biological properties, and different applications have been reported, both for human consumption and animal nutrition. Although a systematic investigation of the chemical constituents of Hedysarum spp. has been performed in order to provide chemotaxonomic evidences for the genus and to support the pharmacological application of several species within the genus, few data are available on the chemical constituents of H. coronarium, and only the content of condensed tannins and flavonoids in leaves has been previously reported. In the present paper, results from a detailed chemical analysis of the extracts from the leaves and flowers of H. coronarium grown wild in southern Italy are presented. Identification of the main specialized metabolites within the chemical classes of flavonoids, proanthocyanidins and saponins, is described, including considerations on their content in the two plant organs. Information acquired from this study expands the knowledge on H. coronarium as a source of valuable phytochemicals for different applications in human and animal health and nutrition.

A new glucosyl flavone, 5,7,2′,5′-tetrahydroxyflavone 7-O-β-d-glucopyranoside, named loeflingiin, together with apigenin 6-C-glucoside (isovitexin), coumarins citropten and isompinellin, triterpenoids betulin and betulinic acid, and a mixture of phytosterols β-sitosterol, stigmasterol and campesterol were isolated for the first time from the leaves of wild Plantago loeflingii L. (Plantaginaceae) collected in the Iraqi Kurdistan region. The plant is used by local people to treat wounds and as a vulnerary remedy. The structures of isolated compounds were determined by spectroscopic analysis. The activities of isovitexin and loeflingiinon the viability of breast (MCF7), ovarian (BG-1), endometrial (Ishikawa), and mesothelioma (IST-MES1) human cancer cells and two normal cell lines were determined with an MTT assay. Notably, the new 7-O-glucosyl flavone showed effects higher than cisplatin against the Ishikawa and IST-MESI cell lines. The significant biological activities exhibited by all the compounds isolated from P. loeflingii provided scientific evidence to support the use of the plant in the Kurdish traditional medicine.

The generation and trapping of two new nitrosocarbonyl intermediates bearing carbohydrate-based chiral substituents is achieved by the mild oxidation of the corresponding nitrile oxides with tertiary amine N-oxides. Their capture with suitable dienes and alkenes afforded the corresponding hetero Diels–Alder cycloadducts and ene adducts from fair to excellent yields. The entire methodology looks highly promising by the easy conversion of aldoximes into hydroxymoyl halides, widening the access to nitrosocarbonyls, versatile tools in organic synthesis.

Human Apolipoprotein E (APOE) is a crucial lipid transport glycoprotein involved in various biological processes, including lipid metabolism, immune response, and neurodegeneration. Elevated APOE levels are linked to poor prognosis in several cancers and increased risk of Alzheimer's disease (AD). Therefore, modulating APOE expression presents a promising therapeutic strategy for both cancer and AD. Considering the pivotal role of G-quadruplex (G4) structures in medicinal chemistry as modulators of gene expression, here we present a newly discovered G-quadruplex (G4) structure within the ApoE gene promoter. Bioinformatic analysis identified 21 potential G4-forming sequences in the ApoE promoter, with the more proximal to the transcription start site, pApoE, showing the highest G-score. Biophysical studies confirmed the folding of pApoE into a stable parallel G4 under physiological conditions, supported by circular dichroism, NMR spectroscopy, UV-melting, and quantitative PCR stop assay. Moreover, the ability to modulate pApoE-G4 folding was demonstrated using G4-stabilizing ligands (HPHAM, Braco19, and PDS), which increased the thermal stability of pApoE-G4. In contrast, peptide nucleic acid conjugates synthesized to disrupt G4 formation, effectively hybridizing with pApoE sequences, confirming the potential to unfold G4 structures. Overall, our findings provide a mainstay for future therapeutic approaches targeting ApoE-G4s to regulate APOE expression, offering potential advancements in cancer and AD treatment.

G-rich repetitive nucleic acid sequences can fold into G-quadruplexes (G4s) upon coordination with potassium ions (K+). Small natural and synthetic molecules (G4 ligands) can bind to and stabilize G4 structures in vitro, thereby interfering with biological processes involving G4-containing genes. Therefore, G4 ligands represent highly valuable tools for unveiling G4 biological functions. Together with non-covalent reversible G4 ligands, reactive compounds capable of forming covalent bonds with G4s upon thermal and photochemical activation represent a new class of promising G4 ligands with the potential to be harnessed for the identification and isolation of G4s from a biological environment. In particular, photoaffinity labelling (PAL) encompasses the potential to obtain spatial and temporal control over the alkylation event. However, to date, only a few examples of covalent G4 ligands for PAL approaches have been described, and very low alkylation yields plague all of them. Herein, the synthesis of new families of photoactivatable G4 ligands functionalized with different warheads (e.g., benzophenones and diazirines) is described, as well as their photoreactivity in the presence of three different G4s: 22AG, cMyc, and 25CEBwt. Among the different compounds, diazirine derivatives displayed the highest G4 selectivity and unprecedented high alkylation yields (up to 70%) together with a remarkable selective N- and O-alkylation reaction only on thymine and guanine nucleobases as identified by using a prototype ligand. These new compounds pave the way for the development of new methodologies, allowing for functional investigation and druggability of G4 in cells.