Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, with no cure and preventive therapy. Misfolding and extracellular aggregation of Amyloid-β (Aβ) peptides are recognized as the main cause of AD progression, leading to the formation of toxic Aβ oligomers and to the deposition of β-amyloid plaques in the brain, representing the hallmarks of AD. Given the urgent need to provide alternative therapies, natural products serve as vital resources for novel drugs. In recent years, several natural compounds with different chemical structures, such as polyphenols, alkaloids, terpenes, flavonoids, tannins, saponins and vitamins from plants have received attention for their role against the neurodegenerative pathological processes. However, only for a small subset of them experimental evidences are provided on their mechanism of action. This review focuses on those natural compounds shown to interfere with Aβ aggregation by direct interaction with Aβ peptide and whose inhibitory mechanism has been investigated by means of biophysical and structural biology experimental approaches. In few cases, the combination of approaches offering a macroscopic characterization of the oligomers, such as TEM, AFM, fluorescence, together with high-resolution methods could shed light on the complex mechanism of inhibition. In particular, solution NMR spectroscopy, through peptide-based and ligand-based observation, was successfully employed to investigate the interactions of the natural compounds with both soluble NMR-visible (monomer and low molecular weight oligomers) and NMR-invisible (high molecular weight oligomers and protofibrils) species. The molecular determinants of the interaction of promising natural compounds are here compared to infer the chemical requirements of the inhibitors and the common mechanisms of inhibition. Most of the data converge to indicate that the Aβ regions relevant to perturb the aggregation cascade and regulate the toxicity of the stabilized oligomers, are the N-term and β1 region. The ability of the natural aggregation inhibitors to cross the brain blood barrier, together with the tactics to improve their low bioavailability are discussed. The analysis of the data ensemble can provide a rationale for the selection of natural compounds as molecular scaffolds for the design of new therapeutic strategies against the progression of early and late stages of AD.

Fibroblast growth factors (FGFs) are recognized targets for the development of therapies against angiogenesis-driven diseases, including cancer. The formation of a ternary complex with the transmembrane tyrosine kinase receptors (FGFRs), and heparan sulphate proteoglycans (HSPGs) is required for FGF2 pro-angiogenic activity. Here by using a combination of techniques including Nuclear Magnetic Resonance, Molecular Dynamics, Surface Plasmon Resonance and cell-based binding assays we clarify the molecular mechanism of inhibition of an angiostatic small molecule, sm27, mimicking the endogenous inhibitor of angiogenesis, thrombospondin-1. NMR and MD data demonstrate that sm27 engages the heparin-binding site of FGF2 and induces long-range dynamics perturbations along FGF2/FGFR1 interface regions. The functional consequence of the inhibitor binding is an impaired FGF2 interaction with both its receptors, as demonstrated by SPR and cell-based binding assays. We propose that sm27 antiangiogenic activity is based on a twofold–direct and allosteric–mechanism, inhibiting FGF2 binding to both its receptors.

Water-blown polyurethane (PU) foams were prepared by bio-polyols from epoxidized linseed oils and caprylic acid in combination with toluene diisocianate (TDI). A series of terpenes (menthol, geraniol, terpineol, and borneol), natural compounds with recognized antibacterial properties, were included in the starting formulations to confer bactericidal properties to the final material. Foams additivated with Irgasan^®, a broad-spectrum antimicrobial molecule, were prepared as reference. The bactericidal activity of foams against planktonic and sessile E. coli (ATCC 11229) and S. aureus (ATCC 6538) was evaluated following a modified AATCC 100-2012 static method. Menthol-additivated foams showed broad-spectrum antibacterial activity, reducing Gram+ and Gram− viability by more than 60%. Foams prepared with borneol and terpineol showed selective antibacterial activity against E. coli and S. aureus, respectively. NMR analysis of foams leaking in water supported a bactericidal mechanism mediated by contact killing rather than molecule release. The results represent the proof of concept of the possibility to develop bio-based PU foams with intrinsic bactericidal properties through a simple and innovative synthetic approach.