1.
Pyranoid Spirosugars as Enzyme Inhibitors.
La Ferla, B, D'Orazio, G
Current organic synthesis. 2021;(1):3-22
Abstract
BACKGROUND Pyranoid spirofused sugar derivatives represent a class of compounds with a significant impact in the literature. From the structural point of view, the rigidity inferred by the spirofused entity has made these compounds object of interest mainly as enzymatic inhibitors, in particular, carbohydrate processing enzymes. Among them glycogen phosphorylase and sodium glucose co-transporter 2 are important target enzymes for diverse pathological states. Most of the developed compounds present the spirofused entity at the C1 position of the sugar moiety; nevertheless, spirofused entities can also be found at other sugar ring positions. The main spirofused entities encountered are spiroacetals/thioacetals, spiro-hydantoin and derivatives, spiro-isoxazolines, spiro-aminals, spiro-lactams, spiro-oxathiazole and spiro-oxazinanone, but also others are present. OBJECTIVES The present review focuses on the most explored synthetic strategies for the preparation of this class of compounds, classified according to the position and structure of the spirofused moiety on the pyranoid scaffold. Moreover, the structures are correlated to their main biological activities or to their role as chiral auxiliaries. CONCLUSION It is clear from the review that, among the different derivatives, the spirofused structures at position C1 of the pyranoid scaffold are the most represented and possess the most relevant enzymatic inhibitor activities. Nevertheless, great efforts have been devoted to the introduction of the spirofused entity also in the other positions, mainly for the preparation of biologically active compounds but also for the synthesis of chiral auxiliaries useful in asymmetric reactions; examples of such auxiliaries are the spirofused chiral 1,3-oxazolidin-2-ones and 1,3-oxazolidine-2-thiones.
2.
bioNMR-based identification of natural anti-Aβ compounds in Peucedanum ostruthium.
Palmioli, A, Bertuzzi, S, De Luigi, A, Colombo, L, La Ferla, B, Salmona, M, De Noni, I, Airoldi, C
Bioorganic chemistry. 2019;:76-86
Abstract
The growing interest in medicinal plants for the identification of new bioactive compounds and the formulation of new nutraceuticals and drugs prompted us to develop a powerful experimental approach allowing the detailed metabolic profiling of complex plant extracts, the identification of ligands of macromolecular targets of biomedical relevance and a preliminary characterization of their biological activity. To this end, we selected Peucedanum ostruthium, a plant traditionally employed in Austria and Italy for its several potential therapeutic applications, as case study. We combined the use of NMR and UPLC-HR-MS for the identification of the metabolites present in its leaves and rhizome extracts. Due to the significant content of polyphenols, particularly chlorogenic acids, recently identified as anti-amyloidogenic compounds, polyphenols-enriched fractions were prepared and tested for their ability to prevent Aβ1-42 peptide aggregation and neurotoxicity in a neuronal human cell line. STD-NMR experiments allowed the detailed identification of Aβ oligomers' ligands responsible for the anti-amyloidogenic activity. These data provide experimental protocols and structural information suitable for the development of innovative molecular tools for prevention, therapy and diagnosis of Alzheimer's disease.
3.
Flavonoids in the Treatment of Alzheimer's and Other Neurodegenerative Diseases.
Airoldi, C, La Ferla, B, D Orazio, G, Ciaramelli, C, Palmioli, A
Current medicinal chemistry. 2018;(27):3228-3246
Abstract
Flavonoids are phytochemicals present in almost all terrestrial plants and, as a consequence, in plant-based foods, and thus consumed by humans through diet. Recent evidences suggest that several flavonoids have positive effects against dementia and Alzheimer's disease, reversing age-related declines in neurocognitive performances. In this review, we provide a general classification of natural and synthetic flavonoids, a description of their physico-chemical properties, in particular their redox properties and stability, and an extensive overview about their biological activities and structure-activity relationship in the field of neurodegenerative diseases. In addition, a section will be dedicated to the synthetic strategies for the preparation of bioactive derivatives. This information will be essential for the design and development of new drugs that can improve brain functions.
4.
A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation.
Mezzasalma, V, Manfrini, E, Ferri, E, Sandionigi, A, La Ferla, B, Schiano, I, Michelotti, A, Nobile, V, Labra, M, Di Gennaro, P
BioMed research international. 2016;2016:4740907
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A controlled balance between the healthy and harmful intestinal bacterial species is fundamental for maintaining a healthy gut. Recent studies have shown a correlation between microbiota imbalance and onset of IBS-related symptoms, however the available data remains limited and inconclusive. The aim of this trial was to assess the efficacy of multispecies probiotic supplementation on the gut microbiota of 150 patients diagnosed with IBS. Participants were randomly divided into three groups receiving either one of two probiotic mixtures or the placebo for 90 days. Stool samples were analysed and both symptom and quality of life questionnaires were recorded. The multispecies probiotic supplementation administered in this study demonstrated significant amelioration of IBS symptoms and improvement in quality of life. This supports the role of the gut microbiome in IBS and the potential role of multispecies probiotics in managing this disorder.
Abstract
Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated. Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics. Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period. Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219.