286 results on '"LA FERLA, B"'
Search Results
102. Mapping the way to process improvement
- Author
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La Ferla, B., primary
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- 2003
- Full Text
- View/download PDF
103. ChemInform Abstract: Easy and Stereoselective Synthesis of the Phosphono Analogue of α ‐L‐Rhamnose 1‐Phosphate
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CIPOLLA, L., primary, LA FERLA, B., additional, NICOTRA, F., additional, and PANZA, L., additional
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- 1997
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- View/download PDF
104. Conversion of lactose into mimics of N-acetyllactosamine
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LUIGI LAY, Cipolla, L., La Ferla, B., Peri, F., Nicotra, F., Lay, L, Cipolla, L, LA FERLA, B, Peri, F, and Nicotra, F
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Lactose, carbohydrates, glycomimetics - Abstract
The α-C-Glycoside of N-acetyllactosamine 8 was synthesised from lactose by acetylation, conversion into the allyl α-C-glycoside 4, exchanging the protecting groups for benzyl ethers, selective deprotection at the gluco-C-2 by iodocyclisation-reductive elimination, and conversion of the free hydroxyl group into an acetamido group by oxidation, oximation, stereoselective reduction and acetylation. Isomerization of the C-glycosidic appendage by conversion into a 2-oxypropyl group and treatment with base gave, after acetylation, the β-C-glycoside of N-acetyllactosamine 11.
105. Erratum: Arabinose-derived bicyclic amino acids - Synthesis, conformational analysis and construction of an αvβ3-selective RGD peptide (Journal of the Chemical Society. Perkin Transactions 1 (2002) (638))
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FRANCESCO PERI, Bassetti, R., Caneva, E., Gioia, L., La Ferla, B., Presta, M., Tanghetti, E., and Nicotra, F.
106. Arabinose-derived bicyclic amino acids: Synthesis, conformational analysis and construction of an αvβ3-selective RGD peptide
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Peri, F., Bassetti, R., Caneva, E., Gioia, L., La Ferla, B., Marco PRESTA, Tanghetti, E., and Nicotra, F.
107. Sugar-derived amino acids: Powerful secondary structure-inducing elements in the design of novel peptidomimetics
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FRANCESCO PERI, Cipolla, L., Forni, E., La Ferla, B., and Nicotra, F.
108. Curcumin derivatives: Aβ-ligands as potential diagnostic and therapeutic tools for alzheimer's disease
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La Ferla, B., Cristina Airoldi, and D Orazio, G.
109. ChemInform Abstract: Direct Synthesis of the Isosteric Phosphono Analogues of α-L-Rhamnose 1-Phosphate and β-L-Fucose 1-Phosphate.
- Author
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CIPOLLA, L., LA FERLA, B., PANZA, L., and NICOTRA, F.
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- 1999
- Full Text
- View/download PDF
110. Nitrogen-Doped Carbon Quantum Dots for Biosensing Applications: The Effect of the Thermal Treatments on Electrochemical and Optical Properties
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Francesco Ghezzi, Riccardo Donnini, Antonio Sansonetti, Umberto Giovanella, Barbara La Ferla, Barbara Vercelli, Ghezzi, F, Donnini, R, Sansonetti, A, Giovanella, U, La Ferla, B, and Vercelli, B
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optical and electrochemical propertie ,Organic Chemistry ,Pharmaceutical Science ,nitrogen-doped carbon quantum dots ,Analytical Chemistry ,hydrothermal synthesi ,hydrothermal synthesis ,Chemistry (miscellaneous) ,thermal treatment ,optical and electrochemical properties ,Drug Discovery ,nitrogen-doped carbon quantum dot ,Molecular Medicine ,Physical and Theoretical Chemistry - Abstract
The knowledge of the ways in which post-synthesis treatments may influence the properties of carbon quantum dots (CDs) is of paramount importance for their employment in biosensors. It enables the definition of the mechanism of sensing, which is essential for the application of the suited design strategy of the device. In the present work, we studied the ways in which post-synthesis thermal treatments influence the optical and electrochemical properties of Nitrogen-doped CDs (N-CDs). Blue-emitting, N-CDs for application in biosensors were synthesized through the hydrothermal route, starting from citric acid and urea as bio-synthesizable and low-cost precursors. The CDs samples were thermally post-treated and then characterized through a combination of spectroscopic, structural, and electrochemical techniques. We observed that the post-synthesis thermal treatments show an oxidative effect on CDs graphitic N-atoms. They cause their partially oxidation with the formation of mixed valence state systems, [CDs]0+, which could be further oxidized into the graphitic N-oxide forms. We also observed that thermal treatments cause the decomposition of the CDs external ammonium ions into ammonia and protons, which protonate their pyridinic N-atoms. Photoluminescence (PL) emission is quenched.
- Published
- 2023
111. Red-Emitting Carbon Quantum Dots for Biomedical Applications: Synthesis and Purification Issues of the Hydrothermal Approach
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Barbara La Ferla, Barbara Vercelli, La Ferla, B, and Vercelli, B
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hydrothermal approache ,red-emitting carbon quantum dot ,General Chemical Engineering ,sustainable strategie ,General Materials Science ,red-emitting carbon quantum dots ,hydrothermal approaches ,sustainable strategies - Abstract
The possibility of performing the synthesis of red-emitting carbon quantum dots (r-CDs), in a well-controllable, large scale and environmentally sustainable way is undoubtedly of fundamental importance, as it will pave the way to their employment in advanced medical large-scale applications. Knowledge of the difficulties involved in producing r-CDs with reproducible optical, structural, and chemical characteristics, might help in their large-scale production, making the process standardizable. In this work, we present an experimental study, also supported by results reported in the literature, on the issues encountered during the synthesis and post-synthesis purification treatments of r-CDS. We focused on the hydrothermal approach as it was found to be more suitable for future large-scale industrial applications. We propose three synthetic strategies and observed that employing p-phenylenediamine (p-PDA), as a precursor, the synthetic process showed low efficiency with low yields of r-CDs, large amounts of unreacted precursor, and reaction intermediates. Changing reaction parameters does not improve performance. The r-CDs obtained using citric acid (CA) and urea, as precursors, resulted to be sensitive to pH and difficult to separate from the reaction mixture. Furthermore, the proposed synthetic strategies show that the hydrothermal preparation of r-CDS requires approaches that are not fully sustainable.
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- 2023
112. Binary Biocompatible CNC–Gelatine Hydrogel as 3D Scaffolds Suitable for Cell Culture Adhesion and Growth
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Ilaria Rivolta, Luca Zoia, Anna Binda, Laura Cipolla, Barbara La Ferla, Zoia, L, Binda, A, Cipolla, L, Rivolta, I, and La Ferla, B
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Technology ,food.ingredient ,Biocompatibility ,Geography, Planning and Development ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Gelatin ,food ,Tissue engineering ,medicine ,Cell adhesion ,cellulose nanocrystals ,chemistry.chemical_classification ,Chemistry ,3D-scaffold, Gelatin, Cellulose Nanocrystals, Tissue Engineering ,technology, industry, and agriculture ,Adhesion ,Polymer ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,gelatine ,Chemical engineering ,Cell culture ,tissue engineering ,3D-scaffold ,Swelling ,medicine.symptom ,0210 nano-technology - Abstract
Binary nano-biocomposite 3D scaffolds of cellulose nanocrystals (CNCs) - gelatin were fabricated without the use of chemical cross-linking additives. Controlled oxidative treatment allowed the introduction of carboxyl or carbonyl functionalities on the surface of CNCs that were responsible for the cross-linking of gelatin polymers. The obtained composites were characterized for their physico-chemical properties, and their biocompatibility towards different cell cultures was eval-uated through MTT and LDH assays, cellular adhesion and proliferation experiments. Gelatin composites reinforced with carbonyl-modified CNCs showed the most performing swell-ing/degradation profile and the most promising adhesion and proliferation properties towards cell lines, suggesting their potential application in the field of tissue engineering
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- 2021
113. Synthesis of C-glycosides from unprotected O-glycosides
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LA FERLA, BARBARA, CIPOLLA, LAURA FRANCESCA, NICOTRA, FRANCESCO, Hogendorf, W, La Ferla, B, Cipolla, LF, Hogendorf, W, Nicotra, F, LA FERLA, B, and Cipolla, L
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no - Published
- 2011
114. Pyranoid Spirosugars as Enzyme Inhibitors
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Barbara La Ferla, Giuseppe D'Orazio, La Ferla, B, and D'Orazio, G
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Stereochemistry ,spiro-isoxazolines ,enzyme inhibitors ,enzyme inhibitor ,Biochemistry ,CHIM/06 - CHIMICA ORGANICA ,Moiety ,Spiro Compounds ,Sugar moiety ,sugar derivatives ,chemistry.chemical_classification ,Molecular Structure ,Processing enzymes ,Glycomimetic ,Glycogen Phosphorylase ,Organic Chemistry ,spirofused ,Sugar derivatives ,Enzyme ,chemistry ,Glycomimetics ,pyranoid structure ,Sugars ,sugar derivative - 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.
- Published
- 2021
115. Synthesis of Allyl and Dec-9-Enyl α-D-Mannopyranosides from D-Mannose
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M. Vacchini, L. Cipolla, R. Guizzardi, B. La Ferla, M. Lahmann, Kosma, P, Wrodnigg, TM, Stutz, A, Vacchini, M, Guizzardi, R, Cipolla, L, La Ferla, B, and Lahmann, M
- Subjects
Mannose derivatives, dec-9-enyl α-D-mannopyranosides ,CHIM/06 - CHIMICA ORGANICA - Published
- 2021
116. Targeting GRP receptor: Design, synthesis and preliminary biological characterization of new non-peptide antagonists of bombesin
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Cristina Airoldi, Martina Arici, Alexandre Orsato, Alessandro Palmioli, Cecilia Ceresa, Paola Coccetti, Barbara La Ferla, Gabriella Nicolini, Marcella Rocchetti, Elisabetta Donzelli, Farida Tripodi, Palmioli, A, Nicolini, G, Tripodi, F, Orsato, A, Ceresa, C, Donzelli, E, Arici, M, Coccetti, P, Rocchetti, M, La Ferla, B, and Airoldi, C
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GRP-R antagonist ,Antineoplastic Agents ,Circular dichroism ,01 natural sciences ,Biochemistry ,Epitope ,Gastrin Releasing Peptide (GRP) ,NMR-based structural and conformational analysi ,chemistry.chemical_compound ,Structure-Activity Relationship ,GRP-R ligand ,GRP receptors (GRP-R) ,CHIM/06 - CHIMICA ORGANICA ,Drug Discovery ,Gastrin-releasing peptide receptor ,Tumor Cells, Cultured ,Humans ,Receptor ,Bombesin (BN) ,Molecular Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Organic Chemistry ,MM and MD conformational studie ,Rational design ,Bombesin ,Biological activity ,Transmembrane protein ,0104 chemical sciences ,Receptors, Bombesin ,010404 medicinal & biomolecular chemistry ,CHIM/08 - CHIMICA FARMACEUTICA ,chemistry ,Drug Design ,Biophysics ,Pharmacophore ,Drug Screening Assays, Antitumor ,hormones, hormone substitutes, and hormone antagonists - Abstract
We report the rational design, synthesis, and in vitro preliminary evaluation of a new small library of non-peptide ligands of Gastrin Releasing Peptide Receptor (GRP-R), able to antagonize its natural ligand bombesin (BN) in the nanomolar range of concentration. GRP-R is a transmembrane G-protein coupled receptor promoting the stimulation of cancer cell proliferation. Being overexpressed on the surface of different human cancer cell lines, GRP-R is ideal for the selective delivery to tumor cells of both anticancer drug and diagnostic devices. What makes very challenging the design of non-peptide BN analogues is that the 3D structure of the GRP-R is not available, which is the case for many membrane-bound receptors. Thus, the design of GRP-R ligands has to be based on the structure of its natural ligands, BN and GRP. We recently mapped the BN binding epitope by NMR and here we exploited the same spectroscopy, combined with MD, to define BN conformation in proximity of biological membranes, where the interaction with GRP-R takes place. The gained structural information was used to identify a rigid C-galactosidic scaffold able to support pharmacophore groups mimicking the BN key residues’ side chains in a suitable manner for binding to GRP-R. Our BN antagonists represent hit compounds for the rational design and synthesis of new ligands and modulators of GRP-R. The further optimization of the pharmacophore groups will allow to increase the biological activity. Due to their favorable chemical properties and stability, they could be employed for the active receptor-mediated targeting of GRP-R positive tumors.
- Published
- 2020
117. PLGA Based Nanoparticles for the Monocyte-Mediated Anti-Tumor Drug Delivery System
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Marina Sironi, Alessandro Palmioli, Barbara La Ferla, Akihiro Maeda, Roberta Avigni, Paola Allavena, Allavena, P, Palmioli, A, Avigni, R, Sironi, M, La Ferla, B, and Maeda, A
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DOXORUBICIN ,0206 medical engineering ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Nanoparticle ,Bioengineering ,Antineoplastic Agents ,macromolecular substances ,02 engineering and technology ,Monocytes ,chemistry.chemical_compound ,Mice ,Drug Delivery Systems ,TUMOR ,Polylactic Acid-Polyglycolic Acid Copolymer ,In vivo ,medicine ,PLGA NP ,Animals ,General Materials Science ,Doxorubicin ,Drug Carriers ,Chemistry ,Monocyte ,technology, industry, and agriculture ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,PLGA ,medicine.anatomical_structure ,LIVE CELL-MEDIATED DRUG DELIVERY ,Toxicity ,Drug delivery ,Cancer research ,Nanoparticles ,0210 nano-technology ,Drug carrier ,medicine.drug - Abstract
Together with the development of new therapeutic agents, innovation in the delivery system of anti-tumor drugs is required to increase tumor-specificity and avoid unexpected toxicity. To achieve higher efficiency, we combined a live cell-mediated drug delivery system with nanotechnology, with the aim to prove that blood monocytes can be a cargo to deliver antitumor drugs encapsulated in Polymeric poly(D, L-lactide-co-glycolide) acid based nanoparticles (PLGA NPs). In this study, we have characterized how isolated purified monocytes efficiently internalize PLGA-NPs and have imaged in vivo their trafficking upon intravenous injection in tumor-bearing mice. Monocytes carrying PLGA-Cy7 NPs were able to reach the tumor site, with superior efficiency than free PLGA-Cy7 NPs, and the bio-distribution analysis confirmed that tumors were the most reached among peripheral tissues. We further demonstrate that monocytes carrying Doxorubicin encapsulated PLGA NPs (PLGA-Doxo) induced strong killing of co-cultured tumor cells. Our studies provide proof-of-concept evidence that monocytes can be exploited in approaches of live cell-mediated drug delivery systems for tumor therapy.
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- 2020
118. Hexosamine pathway inhibition overcomes pancreatic cancer resistance to gemcitabine through unfolded protein response and EGFR-Akt pathway modulation
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Jin Gu, Humberto De Vitto, Yupei Zhao, Ferdinando Chiaradonna, Yang Gang, Barbara La Ferla, Francesca Ricciardiello, Fangyu Zhao, Roberta Palorini, Taiping Zhang, Quanxiao Li, Wenfang Guan, Lei You, Marco Giampà, Ricciardiello, F, Gang, Y, Palorini, R, Li, Q, Giampà, M, Zhao, F, You, L, La Ferla, B, De Vitto, H, Guan, W, Gu, J, Zhang, T, Zhao, Y, and Chiaradonna, F
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0301 basic medicine ,Cancer Research ,Programmed cell death ,endocrine system diseases ,Phosphoacetylglucosamine mutase ,Deoxycytidine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,Pancreatic cancer ,Genetics ,medicine ,Animals ,Humans ,Epidermal growth factor receptor ,Molecular Biology ,PI3K/AKT/mTOR pathway ,biology ,Cell growth ,pancreatic cancer, drug resistance, cancer metabolism ,Hexosamines ,medicine.disease ,Xenograft Model Antitumor Assays ,Gemcitabine ,BIO/10 - BIOCHIMICA ,ErbB Receptors ,Pancreatic Neoplasms ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Unfolded Protein Response ,Unfolded protein response ,Cancer research ,biology.protein ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Different evidence has indicated metabolic rewiring as a necessity for pancreatic cancer (PC) growth, invasion, and chemotherapy resistance. A relevant role has been assigned to glucose metabolism. In particular, an enhanced flux through the Hexosamine Biosynthetic Pathway (HBP) has been tightly linked to PC development. Here, we show that enhancement of the HBP, through the upregulation of the enzyme Phosphoacetylglucosamine Mutase 3 (PGM3), is associated with the onset of gemcitabine (GEM) resistance in PC. Indeed, mRNA profiles of GEM sensitive and resistant patient-derived tumor xenografts (PDXs) indicate that PGM3 expression is specifically increased in GEM-resistant PDXs. Of note, PGM3 results also overexpressed in human PC tissues as compared to paired adjacent normal tissues and its higher expression in PC patients is associated with worse median overall survival (OS). Strikingly, genetic or pharmacological PGM3 inhibition reduces PC cell growth, migration, invasion, in vivo tumor growth and enhances GEM sensitivity. Thus, combined treatment between a specific inhibitor of PGM3, named FR054, and GEM results in a potent reduction of xenograft tumor growth without any obvious side effects in normal tissues. Mechanistically, PGM3 inhibition, reducing protein glycosylation, causes a sustained Unfolded Protein Response (UPR), a significant attenuation of the pro-tumorigenic Epidermal Growth Factor Receptor (EGFR)-Akt axis, and finally cell death. In conclusion this study identifies the HBP as a metabolic pathway involved in GEM resistance and provides a strong rationale for a PC therapy addressing the combined treatment with the PGM3 inhibitor and GEM.
- Published
- 2020
119. Electrochemical Characterization of CdSe Monolayers Modified with Glycosilated Molecules
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B. La Ferla, Gianni Zotti, Barbara Vercelli, Giuseppe D'Orazio, La ferla, B, D'Orazio, G, Zotti, G, and Vercelli, B
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Materials science ,02 engineering and technology ,010402 general chemistry ,Electrochemistry ,01 natural sciences ,Analytical Chemistry ,Cdse nanocrystals ,Jacalin ,Self assembling ,Monolayer ,CdSe Nanocrystals, self-assembling, a-mannose, b-galactose, Jacalin, Cyclic Voltammetry ,Molecule ,β-galactose ,α-mannose ,CdSe Nanocrystals · self-assembling · a-mannose · b-galactose · Jacalin · Cyclic Voltammetry ,021001 nanoscience & nanotechnology ,self-assembling ,0104 chemical sciences ,Characterization (materials science) ,CdSe Nanocrystals ,Chemical engineering ,CdSe Nanocrystal ,Cyclic voltammetry ,Cyclic Voltammetry ,0210 nano-technology - Abstract
Ultrathin films of CdSe nannocrystals (CdSe-NCs) modified with glycosilated molecules have shown interesting electrochemical properties which lead to the detection of lectin Jacalin.
- Published
- 2018
120. Nitrogen-doped carbon quantum dots obtained hydrothermally from citric acid and urea: The role of the specific nitrogen centers in their electrochemical and optical responses
- Author
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Barbara La Ferla, Barbara Vercelli, Antonio Sansonetti, Riccardo Donnini, Umberto Giovanella, Francesco Ghezzi, Vercelli, B, Donnini, R, Ghezzi, F, Sansonetti, A, Giovanella, U, and La Ferla, B
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General Chemical Engineering ,chemistry.chemical_element ,Protonation ,02 engineering and technology ,010402 general chemistry ,Electrochemistry ,01 natural sciences ,Redox ,Hydrothermal circulation ,Catalysis ,chemistry.chemical_compound ,Molecule ,Optical Properties ,Nitrogen-doped Carbon Quantum Dot ,Chemistry ,Hydrothermal Method ,021001 nanoscience & nanotechnology ,Nitrogen ,0104 chemical sciences ,Chemical engineering ,Nitrogen-doped Carbon Quantum Dots ,Redox Center ,Optical Propertie ,Redox Centers ,0210 nano-technology ,Citric acid - Abstract
The knowledge of how the different types of nitrogen centers affect the electrochemical and optical properties of Nitrogen-doped carbon quantum dots (N-CDs) is of paramount importance in the design and synthesis of these nanostructures. In fact, from the knowledge of the redox centers of N-CDs it is possible tune their energetic levels in order to realize the suitable matches for the design of opto-electronic, photovoltaic or catalytic devices. Herein we present a study of the electrochemical and the optical responses of N-CDs, obtained by hydrothermal method from citric acid and urea. The main issue is to investigate the role played by the specific nitrogen centers in their redox processes. From the voltammetric responses we showed that the observed oxidation processes of N-CDs involve their graphitic and pyrrolic N-atoms, respectively, while the reduction process regards their protonated pyridinic N-atoms. Then, from spectro-electrochemical determinations, we explained that the oxidation of the graphitic N-atoms is a two electron process that gives an N-oxide form through the reaction with a molecule of water and the loss of two protons. Finally we discussed the observed pH-dependence of both the optical and the electrochemical responses of our N-CDs to explain the role played by their pyridinic N-atoms.
- Published
- 2021
121. PVP-co-DMAEMA as Novel Polymeric Coating Material for Probiotic Supplements Delivery
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Barbara La Ferla, Jessica Zampolli, Giuseppe D'Orazio, Zahraa Zeaiter, Patrizia Di Gennaro, Alessandra De Giani, D'Orazio, G, De Giani, A, Zampolli, J, Zeaiter, Z, Di Gennaro, P, and La Ferla, B
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Materials science ,Polymers and Plastics ,Organic Chemistry ,polymer coating ,microencapsulation, pH responsiveness, polymer coating, probiotics ,engineering.material ,Condensed Matter Physics ,Microencapsulation ,pH responsiveness ,probiotics ,law.invention ,Probiotic ,Coating ,Chemical engineering ,law ,Polymer chemistry ,Materials Chemistry ,engineering ,Polymer coating ,Physical and Theoretical Chemistry - Abstract
The paper investigates the use of poly(1-vinylpyrrolidone-co-2-dimethylaminoethylmetacrilate) (PVP-co-DMAEMA) as a novel coating agent in the preparation of alginate-based microcapsule for the supplement delivery of probiotics. Probiotic Lactobacillus plantarum is used to study the viability of the encapsulated bacterium when exposed to conditions simulating the gastrointestinal tract and industrial process. Results demonstrate that the PVP-co-DMAEMA polymer constitutes a pH-responsive coating suitable for probiotic supplement delivery.
- Published
- 2019
122. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation
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Anna Sandionigi, Valerio Mezzasalma, Irene Schiano, Enrico Manfrini, Vincenzo Nobile, Patrizia Di Gennaro, Massimo Labra, Emanuele Ferri, Angela Michelotti, Barbara La Ferla, Mezzasalma, V, Manfrini, E, Ferri, E, Sandionigi, A, LA FERLA, B, Schiano, I, Michelotti, A, Nobile, V, Labra, M, and DI GENNARO, P
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Adult ,Male ,probiotics, irritable bowel syndrome, clinical study, microbiota, qPCR ,0301 basic medicine ,medicine.medical_specialty ,Constipation ,Adolescent ,Article Subject ,Placebo-controlled study ,lcsh:Medicine ,Gut flora ,Placebo ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Irritable Bowel Syndrome ,03 medical and health sciences ,Probiotic ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,Oral administration ,law ,Internal medicine ,medicine ,Humans ,Irritable bowel syndrome ,Aged ,General Immunology and Microbiology ,biology ,business.industry ,Probiotics ,lcsh:R ,General Medicine ,Middle Aged ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Dietary Supplements ,Clinical Study ,Female ,medicine.symptom ,Corrigendum ,business ,Follow-Up Studies - 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 numberISRCTN15032219.
- Published
- 2016
123. F-18-labeling syntheses and preclinical evaluation of functionalized nanoliposomes for Alzheimer's disease
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Cristiano Zona, Martti Kaasalainen, Sarita Forsback, Olof Solin, Massimo Masserini, Juha O. Rinne, Anniina Snellman, Merja Haaparanta-Solin, Francesca Re, Jarno Salonen, Francisco R. López-Picón, Barbara La Ferla, Francesco Nicotra, Johanna Rokka, Rokka, J, Snellman, A, Kaasalainen, M, Salonen, J, Zona, C, LA FERLA, B, Nicotra, F, Re, F, Masserini, M, Forsback, S, Lopez Picon, F, Rinne, J, Haaparanta Solin, M, and Solin, O
- Subjects
Male ,0301 basic medicine ,Fluorine Radioisotopes ,Pathology ,Pharmaceutical Science ,02 engineering and technology ,environment and public health ,Mice ,chemistry.chemical_compound ,Tissue Distribution ,ta317 ,Liposome ,Molecular Structure ,medicine.diagnostic_test ,Genes, Transgenic, Suicide ,Brain ,Phosphatidic acid ,Alzheimer's disease ,021001 nanoscience & nanotechnology ,Positron emission tomography ,Positron emission tomography (PET) ,Female ,0210 nano-technology ,Nucleophilic 18F-fluorination ,Biodistribution ,medicine.medical_specialty ,β-amyloid plaques ,β-amyloid plaque ,ta3112 ,03 medical and health sciences ,Alzheimer Disease ,In vivo ,Functionalized nanoliposome ,medicine ,Animals ,Technology, Pharmaceutical ,NLS ,business.industry ,Fluorine ,Nanostructures ,030104 developmental biology ,chemistry ,Positron-Emission Tomography ,Liposomes ,Biophysics ,Curcumin ,Autoradiography ,Radiopharmaceuticals ,business ,Ex vivo - Abstract
The aim of the present study was to synthesize functionalized (18)F-labeled NLs ((18)F-NLs) and evaluate their biological behavior in mouse models of Alzheimer's disease (AD) using positron emission tomography (PET) and ex vivo brain autoradiography. (18)F-fluorine was introduced to (18)F-NLs either by using a core forming (18)F-lipid or by encapsulating a (18)F-tracer, (18)F-treg-curcumin inside the NLs. Phosphatidic acid (PA) and curcumin derivative (Curc) functionalized (18)F-NLs with or without additional mApoE functionalization were produced using thin film hydration. The biodistribution and β-amyloid plaque-binding ability of (18)F-NLs were studied in wild type mice and AD mouse models using in vivo PET imaging and ex vivo brain autoradiography at 60min after (18)F-NL injection. Functionalized (18)F-NLs were successfully synthesized. The preclinical evaluation in mice showed that the functional group affected the biodistribution of (18)F-NLs. Further functionalization with mApoE increased the brain-to-blood ratio of (18)F-NLs but the overall brain uptake remained low with all functionalized (18)F-NLs. The liposomal encapsulation of (18)F-treg-curcumin was not successful and preclinical results of encapsulated (18)F-treg-curcumin and plain (18)F-treg-curcumin were identical. Although the studied functionalized (18)F-NLs were not suitable for PET imaging as such, the synthesis techniques introduced in this study can be utilized to modify the biological behavior of (18)F-labeled NLs.
- Published
- 2016
124. bioNMR-based identification of natural anti-Aβ compounds in Peucedanum ostruthium
- Author
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Cristina Airoldi, Laura Colombo, Mario Salmona, Ivano De Noni, Alessandro Palmioli, Barbara La Ferla, Ada De Luigi, Sara Bertuzzi, Palmioli, A, Bertuzzi, S, De Luigi, A, Colombo, L, La Ferla, B, Salmona, M, De Noni, I, and Airoldi, C
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Peucedanum ostruthium ,Peptide ,Human cell line ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,Nutraceutical ,CHIM/01 - CHIMICA ANALITICA ,Drug Discovery ,Alzheimer’s disease, anti-amyloidogenic compounds, chlorogenic acids, furanocoumarins, NMR spectroscopy, Peucedanum ostruthium, UPLC-HR-MS ,CHIM/06 - CHIMICA ORGANICA ,Structure–activity relationship ,Medicinal plants ,Molecular Biology ,Nuclear Magnetic Resonance, Biomolecular ,chemistry.chemical_classification ,Biological Products ,Amyloid beta-Peptides ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Plant Extracts ,Organic Chemistry ,Biological activity ,CHIM/10 - CHIMICA DEGLI ALIMENTI ,biology.organism_classification ,0104 chemical sciences ,Plant Leaves ,010404 medicinal & biomolecular chemistry ,CHIM/08 - CHIMICA FARMACEUTICA ,Polyphenol ,Apiaceae - 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.
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- 2018
125. Glycofunctionalization of Poly(lactic- co-glycolic acid) Polymers: Building Blocks for the Generation of Defined Sugar-Coated Nanoparticles
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Barbara La Ferla, Alessandro Palmioli, Palmioli, A, and La Ferla, B
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chemistry.chemical_classification ,education ,Organic Chemistry ,technology, industry, and agriculture ,Nanoparticle ,02 engineering and technology ,Polymer ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,Monomer ,chemistry ,Chemical engineering ,Dendrimer ,CHIM/06 - CHIMICA ORGANICA ,poly(lactic-co-glycolic acid), PLGA, chemoselective, glycodendrimers, surface-decorated nanoparticles ,Surface modification ,Monosaccharide ,Physical and Theoretical Chemistry ,0210 nano-technology ,Sugar ,Glycolic acid - Abstract
A set of poly(lactic- co-glycolic acid) polymers functionalized with different monosaccharides as well as glycodendrimers and surface-decorated nanoparticles (NPs) were synthesized and characterized. The functionalization of the polymer was carried out through amide bond formation with amino-modified sugar monomers and through a biocompatible chemoselective method exploiting the reducing end of a free sugar. The assemblage of the NPs adopting a nanoprecipitation method was straightforward and allowed the preparation of sugars/sugar dendrimer coated NPs.
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- 2018
126. Glycan Carriers As Glycotools for Medicinal Chemistry Applications
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Carlotta Ciaramelli, Alessandro Palmioli, Cristina Airoldi, Roberto Guizzardi, Laura Cipolla, Mattia Vacchini, Rana Edwards, Alice Paiotta, Barbara La Ferla, Vacchini, M, Edwards, R, Guizzardi, R, Palmioli, A, Ciaramelli, C, Paiotta, A, Airoldi, C, La Ferla, B, and Cipolla, L
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Glycan ,Dendrimers ,Computer science ,Chemistry, Pharmaceutical ,glycosensor ,02 engineering and technology ,Biosensing Techniques ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Polysaccharides ,CHIM/06 - CHIMICA ORGANICA ,Drug Discovery ,Animals ,Humans ,glyconanoparticle ,Pharmacology ,Drug Carriers ,biology ,glycodendrimer ,Organic Chemistry ,Proteins ,021001 nanoscience & nanotechnology ,3. Good health ,0104 chemical sciences ,glycosylated materials ,biology.protein ,Molecular Medicine ,Nanoparticles ,0210 nano-technology ,Literature survey ,Protein Binding - Abstract
Carbohydrates are one of the most powerful and versatile classes of biomolecules that nature uses to regulate organisms’ biochemistry, modulating plenty of signaling events within cells, triggering a plethora of physiological and pathological cellular behaviors. In this framework, glycan carrier systems or carbohydrate-decorated materials constitute interesting and relevant tools for medicinal chemistry applications. In the last few decades, efforts have been focused, among others, on the development of multivalent glycoconjugates, biosensors, glycoarrays, carbohydrate-decorated biomaterials for regenerative medicine, and glyconanoparticles. This review aims to provide the reader with a general overview of the different carbohydrate carrier systems that have been developed as tools in different medicinal chemistry approaches relying on carbohydrate-protein interactions. Given the extent of this topic, the present review will focus on selected examples that highlight the advancements and potentialities offered by this specific area of research, rather than being an exhaustive literature survey of any specific glyco-functionalized system.
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- 2018
127. Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis
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Giuseppina Votta, Isabella Raccagni, Ferdinando Chiaradonna, Luca De Gioia, Francesca Ricciardiello, Alice Paiotta, Silvia Valtorta, Laura Brunelli, Giuseppe D'Orazio, Rosa Maria Moresco, Barbara La Ferla, Roberta Palorini, Francesca Tinelli, Roberta Pastorelli, Ricciardiello, F, Votta, G, Palorini, R, Raccagni, I, Brunelli, L, Paiotta, A, Tinelli, F, D’Orazio, G, Valtorta, S, De Gioia, L, Pastorelli, R, Moresco, R, La Ferla, B, and Chiaradonna, F
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0301 basic medicine ,Cancer Research ,Immunology ,Triple Negative Breast cancer, Glycosylation, Therapy, Drug Discovery ,Apoptosis ,Triple Negative Breast Neoplasms ,Hexosamine Biosynthetic Pathway ,Article ,Cell Line ,Animals ,Cell Line, Tumor ,Cell Proliferation ,Enzyme Inhibitors ,Female ,Gene Expression Regulation, Neoplastic ,Hexosamines ,Humans ,MCF-7 Cells ,Mice ,Phosphoglucomutase ,Signal Transduction ,Xenograft Model Antitumor Assays ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Breast cancer ,breast cancer ,Settore BIO/10 - Biochimica ,medicine ,lcsh:QH573-671 ,Triple-negative breast cancer ,Neoplastic ,Tumor ,lcsh:Cytology ,Chemistry ,Cancer ,Settore CHIM/06 - Chimica Organica ,Cell Biology ,medicine.disease ,BIO/10 - BIOCHIMICA ,030104 developmental biology ,Gene Expression Regulation ,Cell culture ,Tumor progression ,Cancer cell ,Cancer research ,Unfolded protein response - Abstract
Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression. However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment. Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect. In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival. In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration. Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS. Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
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- 2018
128. Cellulose nanocrystals as promising nano-devices in the biomedical field
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Paolo Bigini, Luca Zoia, Barbara La Ferla, Patrizia Di Gennaro, La Ferla, B, Zoia, L, Bigini, P, and Di Gennaro, P
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Cellulose nanocrystals ,Bone targeting ,Materials science ,CNCs, bone targeting, antibacterial ,Field (physics) ,Nano devices ,Nanotechnology - Abstract
We present our application of cellulose nanocrystals (CNCs) in the biomedical field. With the aim of identifying novel nanoparticles for drug targeting, we fluorescently labelled the CNCs and carried out a biodistribution study in vivo. Results evidence that CNCs have a peculiar and transient tropism to the limb bones that is likely related to the interaction with the Ca2+ deposits in the bone matrix. We also analyzed and demonstrated the ability of CNCs to inhibit bacterial adhesion to host tissue. All these findings, taken together, make these nanoparticles very promising candidate for a potential development of nano-devices toward bone diseases, as well as new antibacterial agents.
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- 2018
129. Evaluation of the probiotic properties of new Lactobacillus and Bifidobacterium strains and their in vitro effect
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I. Presti, Massimo Labra, G. Bizzaro, Valerio Mezzasalma, Giuseppe D'Orazio, P. Di Gennaro, Angela Michelotti, M. Vassallo, Francesco Tursi, S. Giardina, B. La Ferla, Presti, I, D'Orazio, G, Labra, M, LA FERLA, B, Mezzasalma, V, Bizzarro, G, Giardina, S, Michelotti, A, Tursi, F, Vassallo, M, and DI GENNARO, P
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Intestinal microbiota ,Probiotics ,Lactobacillus ,Bifidobacterium ,Gut disorders ,Animals ,Anti-Bacterial Agents ,Antibiosis ,Antioxidants ,Bile Acids and Salts ,Cell Line ,DNA, Bacterial ,DNA, Ribosomal ,Epithelial Cells ,Fibroblasts ,Humans ,Hydrogen-Ion Concentration ,Mice, Inbred BALB C ,Molecular Sequence Data ,RNA, Ribosomal, 16S ,Sequence Analysis, DNA ,Vitamin B Complex ,Gut flora ,Applied Microbiology and Biotechnology ,law.invention ,Mice ,Probiotic ,law ,Medicine ,Inbred BALB C ,Irritable bowel syndrome ,biology ,Bacterial ,gut disorders ,General Medicine ,Bifidobacterium animalis ,Sequence Analysis ,probiotic ,Biotechnology ,16S ,Microbiology ,Lactobacillus rhamnosus ,Ribosomal ,Lactobacillu ,business.industry ,DNA ,biology.organism_classification ,medicine.disease ,RNA ,business ,Lactobacillus plantarum - Abstract
Probiotic ingestion is recommended as a preventive approach to maintain the balance of the intestinal microbiota and to enhance the human well-being. During the whole life of each individual, the gut microbiota composition could be altered by lifestyle, diet, antibiotic therapies and other stress conditions, which may lead to acute and chronic disorders. Hence, probiotics can be administered for the prevention or treatment of some disorders, including lactose malabsorption, acute diarrhoea, irritable bowel syndrome, necrotizing enterocolitis and mild forms of inflammatory bowel disease. The probiotic-mediated effect is an important issue that needs to be addressed in relation to strain-specific probiotic properties. In this work, the probiotic properties of new Lactobacillus and Bifidobacterium strains were screened, and their effects in vitro were evaluated. They were screened for probiotic properties by determining their tolerance to low pH and to bile salts, antibiotic sensitivity, antimicrobial activity and vitamin B8, B9 and B12 production, and by considering their ability to increase the antioxidant potential and to modulate the inflammatory status of systemic-miming cell lines in vitro. Three out of the examined strains presenting the most performant probiotic properties, as Lactobacillus plantarum PBS067, Lactobacillus rhamnosus PBS070 and Bifidobacterium animalis subsp. lactis PBSO75, were evaluated for their effects also on human intestinal HT-29 cell line. The obtained results support the possibility to move to another level of study, that is, the oral administration of these probiotical strains to patients with acute and chronic gut disorders, by in vivo experiments.
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- 2015
130. Flavonoids in the Treatment of Alzheimer's and Other Neurodegenerative Diseases
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Cristina Airoldi, Carlotta Ciaramelli, Barbara La Ferla, Giuseppe D Orazio, Alessandro Palmioli, Airoldi, C, La Ferla, B, D'Orazio, G, Ciaramelli, C, and Palmioli, A
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Analogues ,Disease ,Computational biology ,Biology ,01 natural sciences ,Biochemistry ,Antioxidants ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,Dementia ,Humans ,Analogue ,Pharmacology ,Flavonoids ,Synthetic approaches ,Neurodegenerative Disease ,fungi ,Organic Chemistry ,food and beverages ,Neurodegenerative Diseases ,Alzheimer's disease ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Neuroprotective Agents ,Flavonoid ,Molecular Medicine ,Synthetic approache ,Antioxidant ,Neurocognitive ,Alzheimer’s disease ,030217 neurology & neurosurgery ,Neurodegenerative diseases - 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.
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- 2017
131. Cellulose nanocrystals are effective in inhibiting host cell bacterial adhesion
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Jessica Zampolli, Giuseppe D'Orazio, L. Munizza, Matilde Forcella, B. La Ferla, P. Di Gennaro, Luca Zoia, Paola Fusi, D'Orazio, G, Munizza, L, Zampolli, J, Forcella, M, Zoia, L, Fusi, P, DI GENNARO, P, and LA FERLA, B
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Materials science ,Biomedical Engineering ,Biomaterial ,02 engineering and technology ,General Chemistry ,General Medicine ,Adhesion ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Bacterial cell structure ,0104 chemical sciences ,Cell biology ,Intestinal cell ,Cellulose nanocrystals ,Monolayer ,Fluorescence microscope ,Biophysics ,General Materials Science ,cellulose nanocrystals, bacterial adhesion, inhibition ,0210 nano-technology - Abstract
The use of cellulose nanocrystals (CNCs) as a biomaterial able to inhibit host cell bacterial adhesion is described. Pre-incubation of E. coli ATCC 25922 with a suspension of 0.1% CNCs afforded a significant 2 log reduction of bacterial adhesion to the intestinal cell monolayer HT29. This effect could be attributed to the interaction between the CNCs and the bacterial cell surface as confirmed using fluorescence microscopy experiments.
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- 2017
132. Synthesis and evaluation of a 18F-curcumin derivate for β-amyloid plaque imaging
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Merja Haaparanta-Solin, Barbara La Ferla, Juha O. Rinne, Anniina Snellman, Cristiano Zona, Olof Solin, Johanna Rokka, Gianluigi Forloni, Mario Salmona, Francesco Nicotra, Rokka, J, Snellman, A, Zona, C, LA FERLA, B, Nicotra, F, Salmona, M, Forloni, G, Haaparanta, M, Rinne, J, and Solin, O
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Male ,Fluorine Radioisotopes ,Curcumin ,Transgene ,Metabolite ,Clinical Biochemistry ,Pharmaceutical Science ,Heterologous ,Mice, Transgenic ,Plaque, Amyloid ,ta3112 ,Biochemistry ,Neuroprotection ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,In vivo ,CHIM/06 - CHIMICA ORGANICA ,Drug Discovery ,Animals ,Tissue Distribution ,ta116 ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Amyloid beta-Peptides ,Organic Chemistry ,In vitro ,Rats ,Mice, Inbred C57BL ,chemistry ,Blood-Brain Barrier ,Isotope Labeling ,Positron-Emission Tomography ,Positron emission tomography (PET), Nucleophilic 18F-fluorination, Curcumin, Alzheimer’s disease, Click chemistry, b-Amyloid ,Biophysics ,Molecular Medicine ,Radiopharmaceuticals ,030217 neurology & neurosurgery ,Ex vivo ,Protein Binding - Abstract
Introduction Curcumin is a neuroprotective compound that inhibits the formation of amyloid oligomers and fibrils and binds to β-amyloid plaques in Alzheimer’s disease (AD). We aimed to synthesize an 18F-labeled curcumin derivate ([18F]4) and to characterize its positron emission tomography (PET) tracer-binding properties to β-amyloid plaques in a transgenic APP23 mouse model of AD. Methods We utilized facile one-pot synthesis of [18F]4 using nucleophilic 18F-fluorination and click chemistry. Binding of [18F]4 to β-amyloid plaques in the transgenic APP23 mouse brain cryosections was studied in vitro using heterologous competitive binding against PIB. [18F]4 uptake was studied ex vivo in rodents and in vivo using PET/computed tomography of transgenic APP23 and wild-type control mice. Results The radiochemical yield of [18F]4 was 21 ± 11%, the specific activity exceeded 1 TBq/μmol, and the radiochemical purity exceeded 99.3% at the end of synthesis. In vitro studies of [18F]4 with the transgenic APP23 mouse revealed high β-amyloid plaque binding. In vivo and ex vivo studies demonstrated that [18F]4 has fast clearance from the blood, moderate metabolism but low blood–brain barrier (BBB) penetration. Conclusions [18F]4 was synthesized in high yield and excellent quality. In vitro studies, metabolite profile, and fast clearance from the blood indicated a promising tracer for Aβ imaging. However, [18F]4 has low in vivo BBB penetration and thus further studies are needed to reveal the reason for this and to possibly overcome this issue.
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- 2014
133. Fluorescent amyloid β-peptide ligand derivatives as potential diagnostic tools for Alzheimer’s disease
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Cristina Airoldi, Francesco Nicotra, Barbara La Ferla, F Ornaghi, Francisco Cardona, Laura Colombo, Giulio Sancini, Erika Sironi, Ilaria Cambianica, Mario Salmona, Airoldi, C, Cardona, F, Sironi, E, Colombo, L, Salmona, M, Cambianica, I, Ornaghi, F, Sancini, G, Nicotra, F, and LA FERLA, B
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fluorescent derivative ,Chemistry ,Ligand ,General Chemical Engineering ,General Chemistry ,Diagnostic tools ,Stain ,Fluorescence ,Amyloid β peptide ,In vitro model ,Benzopyran ,chemistry.chemical_compound ,Binding ability ,Biochemistry ,BIO/09 - FISIOLOGIA ,CHIM/06 - CHIMICA ORGANICA ,Aβ-peptide ligand ,glycofused compounds ,Alzheimer’s disease - Abstract
Aβ-peptide ligands based on a cis-glycofused benzopyran structure have been fluorescently labeled using coumarine derivatives. Among the synthesized compounds, two conserved their binding ability to β-amyloid peptides, as shown by NMR experiments. Moreover, exploiting its fluorescent property, it was demonstrated that one of such compounds was able to cross an in vitro model of blood–brain barrier (BBB) and to stain Aβ‑deposits.
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- 2013
134. Synthesis and Preliminary Biological Evaluation of Fluorescent Glycofused Tricyclic Derivatives of Amyloid β-Peptide Ligands
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Mario Salmona, Barbara La Ferla, Giuseppe D'Orazio, Laura Colombo, D'Orazio, G, Colombo, L, Salmona, M, and LA FERLA, B
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Trimethylsilyl ,Stereochemistry ,Ether ,Peptide ,Medicinal chemistry ,Organocatalysis ,Domino reactions ,Fluorescence ,Diagnostic agents ,Amyloid beta-peptides ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Organocatalysi ,CHIM/06 - CHIMICA ORGANICA ,Physical and Theoretical Chemistry ,chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Domino reaction ,Amyloid beta-peptide ,0104 chemical sciences ,Diagnostic agent ,chemistry ,Thioflavin ,Stereoselectivity ,Aldol condensation ,Conjugate - Abstract
Fluorescent glycofused tricyclic compounds were synthesized through the domino conjugate oxa-Michael addition/aldol condensation of 2-hydroxybenzaldehydes with protected 3-oxoglucal by exploiting activation with an organocatalyst. Stereoselectivity was obtained by using (R)-(+)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether as the catalyst. All synthesized compounds presented good optical properties. All compounds were able to bind to synthetic amyloid β 1-42 peptide aggregates and to label amyloid plaques from brain sections of transgenic mice affected with Alzheimer's disease with staining properties comparable to thioflavin T. We synthesize new fluorescent glycofused tricyclic compounds able to bind to synthetic amyloid β 1-42 peptide aggregates and to label amyloid plaques in brain-tissue samples from transgenic mice affected with Alzheimer's disease.
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- 2016
135. N-Spirofused Bicyclic Derivatives of 1-Deoxynojirimycin: Synthesis and Preliminary Biological Evaluation
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Alessandra Polissi, Giuseppe D'Orazio, Giulia Filippi, Alessandra M. Martorana, Luca De Gioia, Barbara La Ferla, D’Orazio, G, Martorana, A, Filippi, G, Polissi, A, De Gioia, L, and La Ferla, B
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Bicyclic molecule ,010405 organic chemistry ,Stereochemistry ,quaternary ammonium salt ,enzymatic inhibitors ,General Chemistry ,Docking calculations ,spirofused ,Iminosugars ,quaternary ammonium salts ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,enzymatic inhibitor ,chemistry.chemical_compound ,chemistry ,docking calculation ,CHIM/06 - CHIMICA ORGANICA ,Iminosugar ,1-Deoxynojirimycin ,Biological evaluation - Abstract
We synthesized a small library of N-spirofused bicyclic derivatives of 1-deoxynojirimycin (DNJ), as quaternary ammonium salts, through a double SN2 annulation process. The spirofused rings are of different size and structural characteristics. Preliminary biological evaluation showed no antibacterial activity towards both Gram+ and Gram- bacteria. The DNJ derivative bearing a 6 member spirofused cycle revealed a promising inhibitor activity towards amyloglucosidase. Binding energies calculated through docking studies resembled the in vitro capability of such compound and of DNJ to inhibit amyloglucosidase activity, while showing significant difference in the binding poses.
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- 2016
136. Curcumin derivatives as new ligands of Aβ peptides
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Cristiano Zona, Dario Aurilia, Erika Sironi, Francesco Nicotra, Mario Salmona, Cristina Airoldi, Massimo Masserini, Barbara La Ferla, Laura Colombo, Maria Gregori, Massimo Messa, Airoldi, C, Zona, C, Sironi, E, Colombo, L, Messa, M, Aurilia, D, Gregori, M, Masserini, M, Salmona, M, Nicotra, F, and LA FERLA, B
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Curcumin ,Stereochemistry ,Alzheimer’s disease, Abeta peptides, Abeta ligands, Curcumin derivatives, NMR interaction studies, Conformational analysis, Brain amyloid plaque staining ,Mice, Transgenic ,Bioengineering ,Molecular Dynamics Simulation ,010402 general chemistry ,01 natural sciences ,Applied Microbiology and Biotechnology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Animals ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,Brain Chemistry ,Amyloid beta-Peptides ,Improved solubility ,Histocytochemistry ,Chemistry ,Aβ peptide ,General Medicine ,Peptide Fragments ,0104 chemical sciences ,3. Good health ,Solubility ,Chemical stability ,030217 neurology & neurosurgery ,Protein Binding ,Biotechnology - Abstract
Curcumin derivatives with high chemical stability, improved solubility and carrying a functionalized appendage for the linkage to other entities, have been synthesized in a straightforward manner. All compounds retained Curcumin ability to bind Aβ peptide oligomers without inducing their aggregation. Moreover all Curcumin derivatives were able to stain very efficiently Aβ deposits. © 2011 Elsevier B.V..
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- 2011
137. Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer's Aβ peptide
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Francesco Nicotra, Spyridon Mourtas, Cristiano Zona, Susan Moore, Barbara La Ferla, David Allsop, Massimo Masserini, Mark Taylor, Anna Niarakis, Maria Gregori, Sophia G. Antimisiaris, Francesca Re, Taylor, M, Moore, S, Mourtas, S, Niarakis, A, Re, F, Zona, C, LA FERLA, B, Nicotra, F, Masserini, M, Antimisiaris, S, Gregori, M, and Allsop, D
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Curcumin ,Materials science ,Cardiolipins ,Biomedical Engineering ,Phosphatidic Acids ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Peptide ,G(M1) Ganglioside ,Ligands ,Fibril ,Oligomer ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Cardiolipin ,Humans ,Amyloid-β ,General Materials Science ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Liposome ,Amyloid beta-Peptides ,Phosphatidic acid ,Peptide Fragments ,chemistry ,Biochemistry ,Liposomes ,Nanoparticles ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,030217 neurology & neurosurgery ,Conjugate - Abstract
The effect of various types of nanoliposomes (associated with curcumin, phosphatidic acid, cardiolipin, or GM1 ganglioside) on the aggregation of the amyloid-β(1-42) (Aβ(1-42)) peptide was investigated. Nanoliposomes incorporating curcumin (curcumin-liposomes) were prepared by adding curcumin in the lipid phase during liposome preparation, whereas curcumin surface-decorated liposomes were prepared by using a curcumin-lipid conjugate (lipid-S-curcumin liposomes) or by attaching a curcumin derivative on preformed liposomes by click chemistry (click-curcumin liposomes). The lipid ligands (phosphatidic acid, cardiolipin, or GM1) were also incorporated into nanoliposomes during their formation. All nanoliposomes with curcumin, or the curcumin derivative, were able to inhibit the formation of fibrillar and/or oligomeric Aβ in vitro. Of the three forms of curcumin liposomes tested, the click-curcumin type was by far the most effective. Liposomes with lipid ligands only inhibited Aβ fibril and oligomer formation at a very high ratio of liposome to peptide. Curcumin-based liposomes could be further developed as a novel treatment for Alzheimer's disease.
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- 2011
138. Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model
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Francesco Nicotra, Giulio Sancini, Barbara La Ferla, Francesca Re, Silvia Sesana, Alfredo Cagnotto, Mario Salmona, Massimo Masserini, Cristiano Zona, Gianluigi Forloni, Maria Gregori, Ilaria Cambianica, Roberta Rigolio, Re, F, Cambianica, I, Zona, C, Sesana, M, Gregori, M, Rigolio, R, LA FERLA, B, Nicotra, F, Forloni, G, Cagnotto, A, Salmona, M, Masserini, M, and Sancini, G
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Pharmaceutical Science ,Medicine (miscellaneous) ,Peptide ,02 engineering and technology ,environment and public health ,law.invention ,Drug Delivery Systems ,law ,BIO/09 - FISIOLOGIA ,CHIM/06 - CHIMICA ORGANICA ,General Materials Science ,chemistry.chemical_classification ,0303 health sciences ,Liposome ,Microscopy, Confocal ,medicine.diagnostic_test ,Brain ,Cell sorting ,021001 nanoscience & nanotechnology ,Flow Cytometry ,brain endothelial cell ,medicine.anatomical_structure ,Biochemistry ,Blood-Brain Barrier ,Molecular Medicine ,0210 nano-technology ,Materials science ,Curcumin ,nanoliposome ,Biomedical Engineering ,Bioengineering ,Blood–brain barrier ,Permeability ,Flow cytometry ,Cell Line ,03 medical and health sciences ,Apolipoproteins E ,Confocal microscopy ,medicine ,NLS ,Animals ,Humans ,ApoE-peptide ,030304 developmental biology ,Endothelial Cells ,Biological Transport ,Rats ,chemistry ,Liposomes ,Biophysics ,Nanoparticles ,Nanocarriers - Abstract
A promising strategy to enhance blood-brain barrier penetration by drugs is the functionalization of nanocarriers with uptake-facilitating ligands. We studied the cellular uptake, by cultured RBE4 brain capillary endothelial cells, of nanoliposomes (NLs) covalently coupled with monomer or tandem dimer of apolipoprotein E (ApoE)-derived peptides (residues 141-150), at various densities. NLs without functionalization did not show either relevant membrane accumulation or cellular uptake, as monitored by confocal microscopy and quantified by fluorescence-activated cell sorting. Functionalization with peptides mediated an efficient NLs uptake that increased with peptide density; NLs carrying monomeric peptide performed the best. Moreover, we studied the ability of ApoE-NLs to enhance the transport of a drug payload through a RBE4 cell monolayer. The permeability of a tritiated curcumin derivative was enhanced after its entrapment into ApoE-NLs, in particular those functionalized with the dimer (+83% with respect to free drug, P < 0.01). Thus, these NLs appear particularly suitable for implementing further strategies for drug brain targeting. From the Clinical Editor: Re and her collaborators present a method for delivering nanoliposomes via the blood brain barrier by utilizing peptide fragments including monomers or tandem dimers ApoE. This method may enable enhanced nanoliposome associated drug delivery via the blood-brain barrier, which would have enormous significance in neurodegenerative and other CNS disorders
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- 2011
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139. Carbohydrate scaffolds in chemical genetic studies
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Cristina Airoldi, Francesco Nicotra, Laura Cipolla, Alexandre Orsato, Cristiano Zona, Nasrin Shaikh, Laura Russo, Barbara La Ferla, Nicotra, F, Cipolla, L, LA FERLA, B, Airoldi, C, Zona, C, Orsato, A, Shaikh, N, and Russo, L
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Magnetic Resonance Spectroscopy ,Combinatorial Chemistry Techniques ,Systems biology ,Carbohydrates ,Chemical genetics, Glycomimetics, Combinatorial library, Akt, NMR ,Bioengineering ,Context (language use) ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Biology ,Ligands ,BIO/10 - BIOCHIMICA ,Applied Microbiology and Biotechnology ,Combinatorial chemistry ,Small molecule ,Genetic Techniques ,CHIM/06 - CHIMICA ORGANICA ,Enzyme Inhibitors ,Chemical genetics ,Topology (chemistry) ,Biotechnology ,Protein ligand - Abstract
Small molecules altering protein functions as inhibitors, agonists or antagonists, find application in systems biology enabling an analysis of the in vivo consequences of these alterations. In this context carbohydrates are ideal tools, not only because they are involved in a variety of recognition phenomena of biological relevance, but also because they are ideal scaffolds to generate libraries of bioactive compounds. Examples of design, synthesis and biological assays of different carbohydrate based inhibitors or protein ligands are reported. Exploiting NMR methods, the binding between a small molecules (inhibitor or ligand) and a protein can be detected, the affinity measured, and the interaction topology defined. This set of information is useful not only to clarify the mechanism of protein-ligand interaction, but also to improve the design of new inhibitors/ligands. The multifunctionality and the conformational rigidity of carbohydrates make this class of compounds the ideal scaffolds to generate libraries exploiting the combinatorial approach. An example of solid phase combinatorial synthesis of a library of 37 compounds is reported.
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- 2009
140. Microencapsulation of new probiotic formulations for gastrointestinal delivery: in vitro study to assess viability and biological properties
- Author
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Angela Michelotti, G. Bizzaro, S. Giardina, M. Boccarusso, Massimo Labra, P. Di Gennaro, B. La Ferla, I. Presti, Giuseppe D'Orazio, D'Orazio, G, DI GENNARO, P, Boccarusso, M, Presti, I, Bizzaro, G, Giardina, S, Michelotti, A, Labra, M, and LA FERLA, B
- Subjects
Oral ,intestinal microbiota ,microencapsulated bacteria ,microencapsulation polymers ,probiotics ,Alginates ,Drug Compounding ,Microencapsulation polymer ,Administration, Oral ,Capsules ,Settore BIO/19 - Microbiologia Generale ,Applied Microbiology and Biotechnology ,Models, Biological ,law.invention ,Microbiology ,Probiotic ,chemistry.chemical_compound ,Lactobacillus rhamnosus ,Glucuronic Acid ,Models ,law ,Humans ,Food science ,Bifidobacterium ,Chitosan ,Microbial Viability ,biology ,Lacticaseibacillus rhamnosus ,Hexuronic Acids ,Probiotics ,General Medicine ,Settore CHIM/06 - Chimica Organica ,Biological ,biology.organism_classification ,Pleuran ,Bifidobacterium animalis ,Gastrointestinal Tract ,chemistry ,Administration ,Intestinal microbiota ,Microencapsulated bacteria ,Microencapsulation polymers ,Lactobacillus plantarum ,Bacteria ,Biotechnology - Abstract
The paper describes the preparation of new probiotic formulations based on chitosan-coated alginate microcapsules containing three different probiotic strains, Lactobacillus plantarum PBS067, Lactobacillus rhamnosus PBS070, and Bifidobacterium animalis subsp. lactis PBS075 taken individually and as a mixture of them. The effects of microencapsulation on the viability of the strains in conditions simulating the gastrointestinal tract and under industrial processes conditions were studied. In addition, an evaluation of their probiotic properties was also investigated by in vitro tests on the human intestinal cell line HT-29 to explore the effect of microencapsulation on health beneficial effect of the considered strains. Non-encapsulated cells were completely destroyed when exposed to simulated gastric juice and other stress conditions, while encapsulated cells exhibited a significantly higher resistance to artificial intestinal juice and heat and osmotic treatment. Moreover, in this study, the effect of the various microencapsulated probiotic strain formulations was compared with analogous formulations also containing the β-glucan Pleuran. The microencapsulation effectively protected the selected bacteria, as single strain and as a mixture of the three strains in both the formulations with and without Pleuran, from simulating gastrointestinal tract and industrial process conditions in delivering the viable cells without any significant adverse effect on their functionalities. The comparative study of the immunomodulatory properties of each single strain and the mixture of the three strains revealed a synergistic effect of the probiotic mixture, but no appreciable difference between the two kinds of formulations could be detected, as the effect of Pleuran is covered by the higher potential of the probiotic strains.
- Published
- 2015
141. arsenical c-glucoside derivatives with promising antitumor activity
- Author
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D'ORAZIO, GIUSEPPE, Parisi, G, Policano, C, Mechelli, R, Codacci Pisanelli, G, Pitaro, M, Ristori, G, Salvetti, M, NICOTRA, FRANCESCO, LA FERLA, BARBARA, D'Orazio, G, Parisi, G, Policano, C, Mechelli, R, Codacci Pisanelli, G, Pitaro, M, Ristori, G, Salvetti, M, Nicotra, F, and LA FERLA, B
- Subjects
Arsenic-glyco derivative ,GLUT transporter ,CHIM/06 - CHIMICA ORGANICA ,Arsenic-glyco derivatives ,antiproliferation ,arsenic ,arsenic-glyco derivatives ,c-glucosides ,organic chemistry ,Antiproliferation ,C-Glucoside ,Arsenic - Abstract
C-Glucoside derivatives covalently linked to the arsenic atom in different oxidation states have been synthesized by avoiding protection-deprotection steps. While compound 1, bearing an AsV atom, did not show any significant biological activity, compound 2, in which the glucose moiety is linked to the arsenic atom as dithioarsenical (AsIII), showed promising antiproliferative activity on a cell line of neuroblastoma (SK-N-BE). C-Glucoside derivatives covalently linked to the arsenic atom in different oxidation states have been synthesized. The C-glucoside conjugated to the phenyldithioarsolan group, showed promising antiproliferative activity on human neuroblastoma cells (SK-N-BE).
- Published
- 2015
142. Combinatorial Approaches to Iminosugars as Glycosidase and Glycosyltransferase Inhibitors
- Author
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Maria Gregori, Barbara La Ferla, Laura Cipolla, Cipolla, L, LA FERLA, B, and Gregori, M
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Glycoside Hydrolases ,Iminosugars ,Iminosugar librarie ,CHIM/06 - CHIMICA ORGANICA ,Drug Discovery ,Glycosyltransferase ,Combinatorial Chemistry Techniques ,Glycoside hydrolase ,Enzyme Inhibitors ,chemistry.chemical_classification ,biology ,Organic Chemistry ,Rational design ,Glycosyltransferases ,Enzyme inhibitor ,General Medicine ,Oligosaccharide ,Imino Sugars ,Glycosidase ,Computer Science Applications ,Enzyme ,Carbohydrate analogue ,chemistry ,Biochemistry ,biology.protein ,Glycoprotein ,Neuraminidase - Abstract
Oligosaccharide processing enzymes such as glycosidases and glycosyltransferases are important classes of biocatalysts involved in synthesising specific oligosaccharide structures on proteins and lipids. These enzymes are known to be involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins, lysosomal catabolism of glycoconjugates and inter-cellular recognition events. Inhibition of these enzymes can disrupt biosynthesis of oligosaccharides, thus interfering in all of these processes. Hence, "glyco-enzyme" inhibitors might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes. This very important prospect has led to increasing interest and demand for these compounds. Interference in oligosaccharide processing is the basis for the anti-influenza neuraminidase inhibitors that have recently been marketed and also for the potential use of glycosidase inhibitors against HIV, Gaucher's disease, hepatitis, and cancer. Since a rational design and synthesis of inhibitors are often extremely difficult due to the limited information regarding the structure of the active site, combinatorial approaches are particularly promising. This review will focus on synthetic efforts for the preparation of combinatorial libraries of glyco-enzyme inhibitors.
- Published
- 2006
143. Carbohydrate‐Based Molecular Scaffolding
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Barbara La Ferla, Ingrid Velter, Francesco Nicotra, Velter, I, LA FERLA, B, and Nicotra, F
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chemistry.chemical_classification ,Scaffold ,Peptidomimetic ,Organic Chemistry ,Polymer ,Carbohydrate ,Biomaterial ,Biochemistry ,Combinatorial chemistry ,Amino acid ,chemistry ,CHIM/06 - CHIMICA ORGANICA ,Iminosugar ,Chemical libraries Glycomimetic ,Organic chemistry ,Sugar ,Sugar amino acids - Abstract
The use of modified carbohydrates, such as sugar amino acids (SAA), iminosugars and policyclic derivatives, as scaffolds for the generation of bioactive compounds, and the use of carbohydrates as building blocks or ligands for the production of polymers for biomedical applications, is reviewed. Copyright © Taylor & Francis Group, LLC.
- Published
- 2006
144. Comparison of Various Types of Ligand Decorated Nanoliposomes for their Ability to Inhibit Amyloid Aggregation and to Reverse Amyloid Cytotoxicity
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Cristiano Zona, Eleni Markoutsa, Erika Bereczki, Jin-Jing Pei, Barbara La Ferla, F Nicotra, Orfeu Flores, Spyridon Mourtas, Sophia G. Antimisiaris, Markoutsa, E, Mourtas, S, Bereczki, E, Zona, C, LA FERLA, B, Nicotra, F, Flores, O, Pei, J, and Antimisiaris, S
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Amyloid ,Curcumin ,Cell Survival ,Drug Evaluation, Preclinical ,Peptide ,Fibril ,Ligands ,Mice ,Alzheimer Disease ,Cell Line, Tumor ,Drug Discovery ,Toxicity Tests ,Animals ,Humans ,MTT assay ,Cytotoxicity ,chemistry.chemical_classification ,Liposome ,Amyloid beta-Peptides ,P3 peptide ,Wild type ,Antibodies, Monoclonal ,General Medicine ,chemistry ,Biochemistry ,Liposomes ,Nanoparticles ,Alzheimer's disease, Amyloid, Aggregation, Curcumin, Liposomes, Monoclonal Antibody, Nanoparticle, Targeting - Abstract
Three different amyloid targeting ligands, previously shown to exhibit amyloid specific properties, have been used to develop amyloid -targeted nanoliposomes (AT-NLs). For this a MAb against Aβ-peptides (Aβ-MAb) (immobilized on NLs at 0.015 and 0.05 mol %), and two different curcumin-lipid derivatives were attached to the surface of preformed NLs or incorporated in NL membranes during their formation. Following physicochemical characterization, these AT-NLs were studied for their ability to inhibit or delay amyloid peptide aggregation –using the thioflavin-T assay, and for their potential to reverse amyloid-induced (and Zn, or, amyloid + Zn) cytotoxicity, on wild type (N2aWT) and transformed (N2aAPP) neuroblastoma cells, applying the MTT assay. Experimental results reveal that all formulations were found to strongly delay amyloid peptide aggregation (with no significant differences between the different AT-NL types). However, although Aβ-MAb-NLs significantly reversed amyloid-induced cytotoxicity in all cases, both curcumin-NL types did not reverse Zn-induced, nor Zn+Aβ-induced cytotoxicity in N2aWT cells, suggesting lower activity against synthetic-Aβ peptides (compared to endogenous Aβ peptides); perhaps due to different affinity towards different (aggregation stages of) peptide species (monomers, oligomers, fibrils, etc). Taken into account that the aggregation stage of amyloid species is an important determinant of their toxicity, the importance of the affinity of each AT-NL type towards specific species, is highlighted.
- Published
- 2014
145. Nanoliposomes presenting on surface a cis-glycofused benzopyran compound display binding affinity and aggregation inhibition ability towards Amyloid b1-42 peptide
- Author
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Spyridon Mourtas, Francesco Nicotra, Cristina Airoldi, Barbara La Ferla, Eleni Markoutsa, Sophia G. Antimisiaris, Francisco Cardona, Giuseppe D'Orazio, Erika Sironi, Cristiano Zona, Airoldi, C, Mourtas, S, RIBEIRO CARDONA, F, Zona, C, Sironi, E, D'Orazio, G, Markoutsa, E, Nicotra, F, Antimisiaris, S, and LA FERLA, B
- Subjects
Protein Structure ,Secondary ,Glycosylation ,Surface Properties ,Stereochemistry ,Peptide ,Stereoisomerism ,Plasma protein binding ,Ligands ,Protein Structure, Secondary ,chemistry.chemical_compound ,Drug Discovery ,CHIM/06 - CHIMICA ORGANICA ,Alzheimer disease (AD) ,Amyloid β (Aβ) ,Copper-free click chemistry ,Glycoderivatives ,Liposomes ,NMR interaction studies ,Amyloid beta-Peptides ,Benzopyrans ,Click Chemistry ,Peptide Fragments ,Protein Binding ,Protein Multimerization ,Nanoparticles ,Pharmacology ,chemistry.chemical_classification ,Liposome ,Alzheimer disease (AD), Amyloid b (Ab), Glycoderivatives, NMR interaction studies, Liposomes, Copper-free click chemistry ,Organic Chemistry ,General Medicine ,Ligand (biochemistry) ,Benzopyran ,chemistry ,Click chemistry ,Biophysics - Abstract
Nanoliposomes decorated on their surface with ligands for Aβ-peptides, the key morphological features of Alzheimer's disease (AD), have been synthesized and characterized for their ability to target Aβ-peptide aggregates. A tricyclic benzopyrane-glycofused structure has been exploited as Aβ-peptide ligand, which was linked to liposomes via a copper-free, chemoselective, biocompatible click chemistry reaction. The tricyclic-decorated liposomes presented a mean diameter in the nanomolar range (150–200 nm), a negative z-potential and a good stability, at least up to one month. Integrity studies performed in the presence of serum proteins indicated that these decorated nanoliposomes fulfill the requirements for in vivo applications. NMR experiments carried out with Aβ 1-42 oligomers using both surface functionalized and plain (control) liposomes, revealed that the binding ability of the nanoliposomes was mediated by the presence of the tricyclic ligand on their surface. Finally ThT assay carried out with tricyclic-decorated liposomes showed significant decrease in thioflavine T fluorescence after 24 h, suggesting a significant inhibition/delay of Aβ 1-42 aggregation.
- Published
- 2014
146. Cis-Glyco-Fused Benzopyran Derivatives as Hit Compounds for the Development of Therapeutic and Diagnostic Tools against Neurodegenerative Diseases
- Author
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Cristina Airoldi, Francisco Cardona, Erika Sironi, Mario Salmona, Barbara La Ferla, Alessandra M. Martorana, Laura Colombo, Silvia Merlo, Merlo, S, Sironi, E, Colombo, L, RIBEIRO CARDONA, F, Martorana, A, Salmona, M, LA FERLA, B, and Airoldi, C
- Subjects
amyloid beta-peptide ,Amyloid ,Chemistry ,Structural similarity ,P3 peptide ,General Chemistry ,Diagnostic tools ,Fibril ,Benzopyran ,chemistry.chemical_compound ,Molecular recognition ,neurodegenerative disease ,NMR spectroscopy ,Biochemistry ,prion protein ,CHIM/06 - CHIMICA ORGANICA ,molecular recognition ,Prion protein - Abstract
Oligomeric and fibrillar aggregates generated by amyloid-β (Aβ) and prion protein (PrP) peptides are amongst the principal components of amyloid plaques found post mortem in patients suffering from Alzheimer’s disease and mammalian prion diseases. Hence these amyloid peptides represent major molecular targets to develop potential drugs and diagnostic tools for the above-mentioned neurodegenerative diseases. Recently, a small library of cis-glyco-fused benzopyran compounds has been synthesized by us, and their ability to recognize and bind Aβ peptide oligomers and stain Aβ deposits was demonstrated. By exploiting the structural similarity between Aβ and PrP aggregates, herein the interaction of these benzopyran molecules with PrP oligomers and their inhibition of the PrP aggregation process that leads to amyloid fibril formation are investigated. Finally, the in vitro staining of PrP fibrils is achieved with a fluorescently labeled cis-glyco-fused benzopyran derivative able to cross a model of the blood–brain barrier.
- Published
- 2014
147. Sodium glucose cotransporter 1 ligand BLF501 as novel tool for management of gastrointestinal mucositis
- Author
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Michele Sommariva, Claudia Sardi, Francesco Nicotra, Cristiano Rumio, Daniela Olivero, Andrea Balsari, Fabrizio Marcucci, Elda Tagliabue, Diego Cardani, Barbara La Ferla, Giuseppe D'Orazio, Hermann Koepsell, Cardani, D, Sardi, C, LA FERLA, B, D'Orazio, G, Sommariva, M, Marcucci, F, Olivero, D, Tagliabue, E, Koepsell, H, Nicotra, F, Balsari, A, and Rumio, C
- Subjects
Cancer Research ,Gastrointestinal Diseases ,Gastrointestinal mucositis ,SGLT-1 ,Synthetic D-glucose analogs ,Chemotherapy ,Inflammation ,Animals ,Antineoplastic Agents ,Blotting, Western ,Cell Line, Tumor ,Disease Models, Animal ,Doxorubicin ,Female ,Fluorescent Antibody Technique ,Fluorouracil ,Glucose ,Heterografts ,Humans ,Immunohistochemistry ,Ligands ,Mice ,Mice, Inbred BALB C ,Mice, Knockout ,Mice, Nude ,Mucositis ,Real-Time Polymerase Chain Reaction ,Sodium-Glucose Transporter 1 ,Transcriptome ,Nude ,Pharmacology ,Intestinal mucosa ,Radixin ,Inbred BALB C ,Gastrointestinal mucositis, SGLT-1, Synthetic D-glucose analogs, Chemotherapy, Inflammation ,Tumor ,medicine.diagnostic_test ,Blotting ,Blot ,Oncology ,Molecular Medicine ,Western ,medicine.drug ,Knockout ,Moesin ,Biology ,Cell Line ,Western blot ,ddc:570 ,medicine ,Animal ,Research ,medicine.disease ,Disease Models ,Immunology - Abstract
Background Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis. Methods Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student’s t-test (paired two-tailed) and χ2 analyses were used for comparisons between groups. Differences were considered significant at p Results BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR. Conclusions BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis.
- Published
- 2014
148. Synthesis and glycosidase inhibition properties of triazole-linked calixarene–iminosugar clusters
- Author
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Alberto Marra, Alessandro Dondoni, Giuseppe D'Orazio, Barbara La Ferla, Renaud Zelli, Marra, A, Zelli, R, D'Orazio, G, LA FERLA, B, and Dondoni, A
- Subjects
1-Deoxynojirimycin derivatives ,biology ,Stereochemistry ,Calix[4]arenes, Clusters, 1-Deoxynojirimycin derivatives, Glycosidases inhibitors, Iminosugars ,Organic Chemistry ,Iminosugar ,Triazole ,Calix[4]arenes ,chemistry.chemical_element ,Clusters ,Glycosidases inhibitors ,Iminosugars ,biology.organism_classification ,Biochemistry ,Copper ,Cycloaddition ,chemistry.chemical_compound ,Cone conformation ,chemistry ,Canavalia ensiformis ,Drug Discovery ,Calixarene ,CHIM/06 - CHIMICA ORGANICA ,Glycoside hydrolase - Abstract
Calixarene–iminosugar derivatives bearing four 1-deoxynojirimycin units at the upper or lower rim of calix[4]arenes in a fixed cone conformation were synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and their inhibitory activity was evaluated against five glycosidases. Modest but significant affinity enhancements of up to seven per 1-deoxynojirimycin unit over the monovalent iminosugar derivative were observed for the inhibition of Jack bean ( Canavalia ensiformis ) α-mannosidase. It was also demonstrated that the residual copper ions did not contribute to the inhibitory properties of the newly prepared calixarene-based multivalent iminosugars.
- Published
- 2014
149. Regioselective lipase acylation as a useful tool for separation and selective protection of β-d-Gal(1→4)-d-GlcNAc and β-d-Gal(1→3)-d-GlcNAc disaccharides
- Author
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Barbara La Ferla, Giovanni Russo, Luigi Panza, Luigi Lay, LA FERLA, B, Lay, L, Russo, G, and Panza, L
- Subjects
chemistry.chemical_classification ,biology ,Stereochemistry ,Organic Chemistry ,regioselectivity, carbohydrate ,Regioselectivity ,Carbohydrate ,biology.organism_classification ,Catalysis ,Inorganic Chemistry ,Acylation ,Enzyme ,chemistry ,biology.protein ,Candida antarctica ,Physical and Theoretical Chemistry ,Lipase ,Selectivity - Abstract
Supported lipase from Candida antarctica (Chirazyme®) was employed for a regioselective protection of the 2-azido derivatives 1 and 2, synthetic equivalents of β-D-Gal(1→3)-D-GlcNAc and β-D-Gal(1→4)-D-GlcNAc (N-acetyl lactosamine), respectively. The selectivity of the enzyme towards 1 and 2 was also exploited for an easy separation of the mixture of the two compounds obtained from a straightforward synthetic approach. Copyright (C) 2000 Elsevier Science Ltd.
- Published
- 2000
150. Easy Silica Gel Supported Desymmetrization of PEG
- Author
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Francesco Nicotra, Barbara La Ferla, Cristiano Zona, LA FERLA, B, Zona, C, and Nicotra, F
- Subjects
chemistry.chemical_classification ,010407 polymers ,010405 organic chemistry ,Silica gel ,Organic Chemistry ,Hydroxy group ,technology, industry, and agriculture ,monoprotection, desymmetrisation, PEG ,Polymer ,01 natural sciences ,Desymmetrization ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,CHIM/06 - CHIMICA ORGANICA ,PEG ratio ,Polymer chemistry ,Organic chemistry ,Ethylene glycol - Abstract
Our work shows how poly(ethylene glycol), differentially functionalized at two ends, can be easily and efficiently synthesized from commercial symmetric dihydroxy PEG 600. First, we linked the polymer onto functionalized silica gel using one of its hydroxy ends. Then, the second hydroxy group was modified, and finally, the desymmetrized PEG was cleaved from the solid support.
- Published
- 2009
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