65 results on '"Ciaramelli, C"'
Search Results
2. Cell-Free and In Vivo Characterization of the Inhibitory Activity of Lavado Cocoa Flavanols on the Amyloid Protein Ataxin-3: Toward New Approaches against Spinocerebellar Ataxia Type 3
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Sciandrone, B, Palmioli, A, Ciaramelli, C, Pensotti, R, Colombo, L, Regonesi, M, Airoldi, C, Sciandrone, Barbara, Palmioli, Alessandro, Ciaramelli, Carlotta, Pensotti, Roberta, Colombo, Laura, Regonesi, Maria Elena, Airoldi, Cristina, Sciandrone, B, Palmioli, A, Ciaramelli, C, Pensotti, R, Colombo, L, Regonesi, M, Airoldi, C, Sciandrone, Barbara, Palmioli, Alessandro, Ciaramelli, Carlotta, Pensotti, Roberta, Colombo, Laura, Regonesi, Maria Elena, and Airoldi, Cristina
- Abstract
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder characterized by ataxia and other neurological manifestations, with a poor prognosis and a lack of effective therapies. The amyloid aggregation of the ataxin-3 protein is a hallmark of SCA3 and one of the main biochemical events prompting its onset, making it a prominent target for the development of preventive and therapeutic interventions. Here, we tested the efficacy of an aqueous Lavado cocoa extract and its polyphenolic components against ataxin-3 aggregation and neurotoxicity. The combination of biochemical assays and atomic force microscopy morphological analysis provided clear evidence of cocoa flavanols’ ability to hinder ATX3 amyloid aggregation through direct physical interaction, as assessed by NMR spectroscopy. The chemical identity of the flavanols was investigated by ultraperformance liquid chromatography-high-resolution mass spectrometry. The use of the preclinical model Caenorhabditis elegans allowed us to demonstrate cocoa flavanols’ ability to ameliorate ataxic phenotypes in vivo. To the best of our knowledge, Lavado cocoa is the first natural source whose extract is able to directly interfere with ATX3 aggregation, leading to the formation of off-pathway species.
- Published
- 2024
3. Antarctic Soil Metabolomics: A Pilot Study
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Ciaramelli, C, Palmioli, A, Brioschi, M, Viglio, S, D’Amato, M, Iadarola, P, Tosi, S, Zucconi, L, Airoldi, C, Ciaramelli C., Palmioli A., Brioschi M., Viglio S., D’Amato M., Iadarola P., Tosi S., Zucconi L., Airoldi C., Ciaramelli, C, Palmioli, A, Brioschi, M, Viglio, S, D’Amato, M, Iadarola, P, Tosi, S, Zucconi, L, Airoldi, C, Ciaramelli C., Palmioli A., Brioschi M., Viglio S., D’Amato M., Iadarola P., Tosi S., Zucconi L., and Airoldi C.
- Abstract
In Antarctica, ice-free areas can be found along the coast, on mountain peaks, and in the McMurdo Dry Valleys, where microorganisms well-adapted to harsh conditions can survive and reproduce. Metabolic analyses can shed light on the survival mechanisms of Antarctic soil communities from both coastal sites, under different plant coverage stages, and inner sites where slow-growing or dormant microorganisms, low water availability, salt accumulation, and a limited number of primary producers make metabolomic profiling difficult. Here, we report, for the first time, an efficient protocol for the extraction and the metabolic profiling of Antarctic soils based on the combination of NMR spectroscopy and mass spectrometry (MS). This approach was set up on samples harvested along different localities of Victoria Land, in continental Antarctica, devoid of or covered by differently developed biological crusts. NMR allowed for the identification of thirty metabolites (mainly sugars, amino acids, and organic acids) and the quantification of just over twenty of them. UPLC-MS analysis identified more than twenty other metabolites, in particular flavonoids, medium- and long-chain fatty acids, benzoic acid derivatives, anthracenes, and quinones. Our results highlighted the complementarity of the two analytical techniques. Moreover, we demonstrated that their combined use represents the “gold standard” for the qualitative and quantitative analysis of little-explored samples, such as those collected from Antarctic soils.
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- 2023
4. NMR-based Ligand–Receptor Interaction Studies under Conventional and Unconventional Conditions
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Ciaramelli, C, Palmioli, A, Airoldi, C, Bhunia, A, Atreya, HS, Sinha, N, Ciaramelli, C, Palmioli, A, and Airoldi, C
- Subjects
CHIM/08 - CHIMICA FARMACEUTICA ,CHIM/01 - CHIMICA ANALITICA ,CHIM/06 - CHIMICA ORGANICA ,molecular recognition, ligand-receptor studies, NMR spectroscopy - Abstract
Many biologically relevant molecular recognition processes are highly dynamic and rely on the equilibrium between ligands’ association and dissociation from their receptor(s), because of the reversible nature of the majority of them. Over the last few decades, several NMR experiments allowing the characterization of these interactions have been developed. They are very useful tools for the study of naturally occurring binding events, but also for the screening of both natural and synthetic compounds that, through the interaction with relevant targets, can exert biological and pharmacological activities. The aim of this chapter is to provide a general presentation of the most commonly used NMR experiments based on ligand resonance observation, together with the descriptions of specific examples of their advanced applications in the analysis of unconventional samples, such as those containing complex compound mixtures, multivalent ligands, liposomes, nanoparticles and living cells.
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- 2022
5. NMR-based Ligand–Receptor Interaction Studies under Conventional and Unconventional Conditions
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Bhunia, A, Atreya, HS, Sinha, N, Ciaramelli, C, Palmioli, A, Airoldi, C, Bhunia, A, Atreya, HS, Sinha, N, Ciaramelli, C, Palmioli, A, and Airoldi, C
- Abstract
Many biologically relevant molecular recognition processes are highly dynamic and rely on the equilibrium between ligands’ association and dissociation from their receptor(s), because of the reversible nature of the majority of them. Over the last few decades, several NMR experiments allowing the characterization of these interactions have been developed. They are very useful tools for the study of naturally occurring binding events, but also for the screening of both natural and synthetic compounds that, through the interaction with relevant targets, can exert biological and pharmacological activities. The aim of this chapter is to provide a general presentation of the most commonly used NMR experiments based on ligand resonance observation, together with the descriptions of specific examples of their advanced applications in the analysis of unconventional samples, such as those containing complex compound mixtures, multivalent ligands, liposomes, nanoparticles and living cells.
- Published
- 2022
6. Metabolomic profiling of beers: Combining 1H NMR spectroscopy and chemometric approaches to discriminate craft and industrial products
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Palmioli, A, Alberici, D, Ciaramelli, C, Airoldi, C, Palmioli, Alessandro, Alberici, Diego, Ciaramelli, Carlotta, Airoldi, Cristina, Palmioli, A, Alberici, D, Ciaramelli, C, Airoldi, C, Palmioli, Alessandro, Alberici, Diego, Ciaramelli, Carlotta, and Airoldi, Cristina
- Abstract
The authentication and traceability of craft beers is an important issue for both beer consumers and producers. Reliable analytical methods able to identify and discriminate products are needed to protect the craft brew market against fraud and counterfeit. Here, 1H NMR analysis of 31 beer samples, differing for beer style and brewing method (craft or industrial) was combined with multivariate statistical analysis, following both an untargeted and a targeted approach. NMR-based analysis of beer samples was sped developing a specific protocol enabling the automatic identification and quantification of metabolites in approximately thirty seconds per spectrum. A clear discrimination was achieved by exploiting 1H NMR analysis and multivariate chemometric methods and the targeted approach identified the metabolites responsible for the segregation. Overall, this study reports an analytical approach addressing beer traceability and is the starting point for the development of a standardized protocol for the discrimination of industrial and craft beers.
- Published
- 2020
7. Coffee variety, origin and extraction procedure: Implications for coffee beneficial effects on human health
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Ciaramelli, C, Palmioli, A, Airoldi, C, Ciaramelli, C, Palmioli, A, and Airoldi, C
- Abstract
We set up an efficient protocol for the rapid analysis of NMR spectra of green and roasted coffee extracts, enabling the automatic identification and quantification of metabolites in approximately two minutes per spectrum. This method allowed for the metabolic profiling and the subsequent evaluation of the content of bioactive compounds and antioxidant activity of coffee samples, depending on their species (Arabica and Robusta), geographical origin and extraction procedure (hydroalcoholic, espresso and moka). The hydroalcoholic extraction is the most efficient method in terms of yields of low molecular weight compounds (in particular chlorogenic acids), while moka extraction provides the highest amounts of melanoidins. Moreover, that the ratio between health-giving compounds (chlorogenic acids, trigonelline and choline) and caffeine is higher in Arabica coffees. The data collected provide useful insights for the selection of coffee raw material to be used in the preparation of coffee-based dietary supplements, nutraceuticals and functional beverages.
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- 2019
8. Nuclear Magnetic Resonance as an Attractive Resource for Monitoring Surveillance Candidates of Acute and Chronic Lung Disorders
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Viglio, S, Airoldi, C, Ciaramelli, C, Iadarola, P, Viglio, S, Airoldi, C, Ciaramelli, C, and Iadarola, P
- Abstract
Metabolomics is the comprehensive study of metabolites, i.e. substrates and end-products of cell metabolism. These are low-molecular weight molecules which include amino, nucleic and organic acids, peptides, carbohydrates, vitamins, polyphenols, alkaloids and inorganic species. Being metabolite concentration influenced by both genetic and environmental factors, their amount directly reflects the underlying biochemical activity and state of cells, tissues or organisms. Profiling the metabolome could thus represent the molecular phenotype better than other approaches such as genomics and proteomics. Among the available procedures (Gas Chromatography-/Liquid Chromatography-Mass Spectrometry), high-resolution nuclear magnetic resonance spectroscopy (HR-NMR) is currently one of the leading analytical tools for metabolomic research due to its peculiarities. The distinctive advantage of NMR over other methods is the possibility to perform an inherent quantitative and untargeted analysis, also with respect to the chemical nature of metabolites. In addition, NMR shows a good reproducibility, a rapid acquisition time of spectra, and it is not destructive with regard to the sample for which little or no preparation is required. Taken together, these features have promoted NMR-assisted metabolomics to the rank of a valuable method for an efficient investigation of a variety of lung diseases. s S sAim of this chapter is to provide an overview of the applications of metabolomics to the study of acute and chronic lung disorders. Why focus on pulmonary disorders? First, by involving tens of million people, lung diseases are some of the most common medical conditions in the world. Second, the depth of analysis ultimately reached by current metabolomic procedures has provided a new and larger context for future studies on the biology of these conditions. This has allowed for the generation of metabolite profiles that could be useful for exploring pathological mechanisms and/or discov
- Published
- 2019
9. Glycan carriers as glycotools for medicinal chemistry applications
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Vacchini, M, Edwards, R, Guizzardi, R, Palmioli, A, Ciaramelli, C, Paiotta, A, Airoldi, C, La Ferla, B, Cipolla, L, Vacchini, Mattia, Edwards, Rana, Guizzardi, Roberto, Palmioli, Alessandro, Ciaramelli, Carlotta, Paiotta, Alice, Airoldi, Cristina, La Ferla, Barbara, Cipolla, Laura, Vacchini, M, Edwards, R, Guizzardi, R, Palmioli, A, Ciaramelli, C, Paiotta, A, Airoldi, C, La Ferla, B, Cipolla, L, Vacchini, Mattia, Edwards, Rana, Guizzardi, Roberto, Palmioli, Alessandro, Ciaramelli, Carlotta, Paiotta, Alice, Airoldi, Cristina, La Ferla, Barbara, and Cipolla, Laura
- 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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- 2019
10. Natural compounds in cancer prevention: effects of coffee extracts and their main polyphenolic component 5-CQA on oncogenic Ras proteins
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Palmioli, A, Ciaramelli, C, Tisi, R, Spinelli, M, De Sanctis, G, Sacco, E, Airoldi, C, Palmioli, A, Ciaramelli, C, Tisi, R, Spinelli, M, De Sanctis, G, Sacco, E, and Airoldi, C
- Subjects
cancer prevention, chlorogenic acid, coffee extracts, NMR molecular recognition studies, Ras proteins ,CHIM/06 - CHIMICA ORGANICA ,BIO/10 - BIOCHIMICA - Abstract
Recent epidemiological studies have demonstrated that the consumption of healthy foods that are particularly rich in polyphenols might reduce the incidence of cancer and neurodegenerative diseases. In particular, chlorogenic acids (CGAs) occur ubiquitously in food and represent the most abundant polyphenols in the human diet. A number of beneficial biological effects of CGAs, such as anti-inflammatory activity, anti-carcinogenic activity, and protection against neurodegenerative diseases, have been reported. However, the molecular mechanisms at the base of these biological activities have not yet been investigated in depth. By combining NMR spectroscopy, molecular docking, surface plasmon resonance and ex vivo assays of the Ras-dependent breast cancer cell line MDA-MB-231, we contribute to the elucidation of the molecular basis of the activity of CGAs and natural extracts from green and roasted coffee beans as chemoprotective dietary supplements.
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- 2017
11. Structure–Activity Relationship in Monosaccharide-Based Toll-Like Receptor 4 (TLR4) Antagonists
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Facchini, F, Zaffaroni, L, Minotti, A, Rapisarda, S, Calabrese, V, Forcella, M, Fusi, P, Airoldi, C, Ciaramelli, C, Billod, J, Schromm, A, Braun, H, Palmer, C, Beyaert, R, Lapenta, F, Jerala, R, Pirianov, G, Martin-Santamaria, S, Peri, F, Facchini, FA, Billod, JM, Schromm, AB, Facchini, F, Zaffaroni, L, Minotti, A, Rapisarda, S, Calabrese, V, Forcella, M, Fusi, P, Airoldi, C, Ciaramelli, C, Billod, J, Schromm, A, Braun, H, Palmer, C, Beyaert, R, Lapenta, F, Jerala, R, Pirianov, G, Martin-Santamaria, S, Peri, F, Facchini, FA, Billod, JM, and Schromm, AB
- Abstract
The structure-activity relationship was investigated in a series of synthetic TLR4 antagonists formed by a glucosamine core linked to two phosphate esters and two linear carbon chains. Molecular modeling showed that the compounds with 10, 12, and 14 carbons chains are associated with higher stabilization of the MD-2/TLR4 antagonist conformation than in the case of the C16 variant. Binding experiments with human MD-2 showed that the C12 and C14 variants have higher affinity than C10, while the C16 variant did not interact with the protein. The molecules, with the exception of the C16 variant, inhibited the LPS-stimulated TLR4 signal in human and murine cells, and the antagonist potency mirrored the MD-2 affinity calculated from in vitro binding experiments. Fourier-transform infrared, nuclear magnetic resonance, and small angle X-ray scattering measurements suggested that the aggregation state in aqueous solution depends on fatty acid chain lengths and that this property can influence TLR4 activity in this series of compounds.
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- 2018
12. Flavonoids in the treatment of alzheimer’s and other neurodegenerative diseases
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Airoldi, C, La Ferla, B, D'Orazio, G, Ciaramelli, C, Palmioli, A, Airoldi, C, La Ferla, B, D'Orazio, G, Ciaramelli, C, and Palmioli, A
- 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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- 2018
13. HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders
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Zeinolabediny, Y, Caccuri, F, Colombo, L, Morelli, F, Romeo, M, Rossi, A, Schiarea, S, Ciaramelli, C, Airoldi, C, Weston, R, Donghui, L, Krupinski, J, Corpas, R, Garcia Lara, E, Sarroca, S, Sanfeliu, C, Slevin, M, Caruso, A, Salmona, M, Diomede, L, Diomede, L., CIARAMELLI, CARLOTTA, AIROLDI, CRISTINA, Zeinolabediny, Y, Caccuri, F, Colombo, L, Morelli, F, Romeo, M, Rossi, A, Schiarea, S, Ciaramelli, C, Airoldi, C, Weston, R, Donghui, L, Krupinski, J, Corpas, R, Garcia Lara, E, Sarroca, S, Sanfeliu, C, Slevin, M, Caruso, A, Salmona, M, Diomede, L, Diomede, L., CIARAMELLI, CARLOTTA, and AIROLDI, CRISTINA
- Abstract
Human immunodeficiency virus type-1 (HIV-1)-Associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies in vitro. To provide new information into the potential pathogenic role of soluble p17 species in HAND, their toxicological capability was evaluated in vivo. In C. elegans, capable of recognising toxic assemblies of amyloidogenic proteins, p17 induces a specific toxic effect which can be counteracted by tetracyclines, drugs able to hinder the formation of large oligomers and consequently amyloid fibrils. The intrahippocampal injection of p17 in mice reduces their cognitive function and induces behavioral deficiencies. These findings offer a new way of thinking about the possible cause of neurodegeneration in HIV-1-seropositive patients, which engages the ability of p17 to form soluble toxic assemblies.
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- 2017
14. Green coffee extract enhances oxidative stress resistance and delays aging in Caenorhabditis elegans
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Amigoni, L, Stuknytė, M, Ciaramelli, C, Magoni, C, Bruni, I, De Noni, I, Airoldi, C, Regonesi, M, Palmioli, A, AMIGONI, LOREDANA, CIARAMELLI, CARLOTTA, MAGONI, CHIARA, BRUNI, ILARIA, AIROLDI, CRISTINA, REGONESI, MARIA ELENA, PALMIOLI, ALESSANDRO, Amigoni, L, Stuknytė, M, Ciaramelli, C, Magoni, C, Bruni, I, De Noni, I, Airoldi, C, Regonesi, M, Palmioli, A, AMIGONI, LOREDANA, CIARAMELLI, CARLOTTA, MAGONI, CHIARA, BRUNI, ILARIA, AIROLDI, CRISTINA, REGONESI, MARIA ELENA, and PALMIOLI, ALESSANDRO
- Abstract
Nutritional factors play a pivotal role for healthy aging and longevity. This is related to the antioxidant properties of the molecules present in some foods. Due to the high content of polyphenols, Green Coffee Extract (GCE) is a powerful antioxidant. Nevertheless, little is known about its effect on aging. We demonstrated the benefic effects of GCE on stress resistance, fertility and adult mean lifespan using Caenorhabditis elegans as a model. The mean and maximum lifespan of worms treated with GCE increased significantly in a dose-dependent manner, and animals pre-treated were more resistant to oxidative stress. NMR and UPLC/ESI-HRMS analyses of GCE confirmed a significant content of chlorogenic acids, being 5-O-caffeoylquinic acid (5-CQA) the most abundant isomer. The major activity demonstrated by GCE in comparison to the pure 5-CQA on C. elegans phenotypes clearly demonstrated the importance of the employment of a natural extract to develop functional foods and supplements.
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- 2017
15. 1H NMR to Evaluate the Metabolome of Bronchoalveolar Lavage Fluid (BALf) in Bronchiolitis Obliterans Syndrome (BOS): Toward the Development of a New Approach for Biomarker Identification
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Ciaramelli, C, Fumagalli, M, Viglio, S, Bardoni, A, Piloni, D, Meloni, F, Iadarola, P, Airoldi, C, Ciaramelli, C, Fumagalli, M, Viglio, S, Bardoni, A, Piloni, D, Meloni, F, Iadarola, P, and Airoldi, C
- Abstract
This report describes the application of NMR spectroscopy to the profiling of metabolites in bronchoalveolar lavage fluid (BALf) of lung transplant recipients without bronchiolitis obliterans syndrome (BOS) (stable, S, n = 10), and with BOS at different degrees of severity (BOS 0p, n = 10; BOS I, n = 10). Through the fine-tuning of a number of parameters concerning both sample preparation/processing and variations of spectra acquisition modes, an efficient and reproducible protocol was designed for the screening of metabolites in a pulmonary fluid that should reflect the status of airway inflammation/injury. Exploiting the combination of mono- and bidimensional NMR experiments, 38 polar metabolites, including amino acids, Krebs cycle intermediates, mono- and disaccharides, nucleotides, and phospholipid precursors, were unequivocally identified. To determine which signature could be correlated with the onset of BOS, the metabolites' content of the above recipients was analyzed by multivariate (PCA and OPLS-DA) statistical methods. PCA analysis (almost) totally differentiated S from BOS I, and this discrimination was significantly improved by the application of OPLS-DA, whose model was characterized by excellent fit and prediction values (R2 = 0.99 and Q2 = 0.88). The analysis of S vs BOS 0p and of BOS 0p vs BOS I samples showed a clear discrimination of considered cohorts, although with a poorer efficiency compared to those measured for S vs BOS I patients. The data shown in this work assess the suitability of the NMR approach in monitoring different pathological lung conditions.
- Published
- 2017
16. Glycolipid-based TLR4 Modulators and Fluorescent Probes: Rational Design, Synthesis, and Biological Properties
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Ciaramelli, C, Calabrese, V, Sestito, S, Pérez Regidor, L, Klett, J, Oblak, A, Jerala, R, Piazza, M, Martín Santamaría, S, Peri, F, CIARAMELLI, CARLOTTA, CALABRESE, VALENTINA, SESTITO, STEFANIA ENZA, PIAZZA, MATTEO, PERI, FRANCESCO, Ciaramelli, C, Calabrese, V, Sestito, S, Pérez Regidor, L, Klett, J, Oblak, A, Jerala, R, Piazza, M, Martín Santamaría, S, Peri, F, CIARAMELLI, CARLOTTA, CALABRESE, VALENTINA, SESTITO, STEFANIA ENZA, PIAZZA, MATTEO, and PERI, FRANCESCO
- Abstract
The cationic glycolipid IAXO-102, a potent TLR4 antagonist targeting both MD-2 and CD14 co-receptors, has been used as scaffold to design new potential TLR4 modulators and fluorescent labels for the TLR4 receptor complex (membrane TLR4.MD-2 dimer and CD14). The primary amino group of IAXO-102, not involved in direct interaction with MD-2 and CD14 receptors, has been exploited to covalently attach a fluorescein (molecules 1 and 2) or to link two molecules of IAXO-102 through diamine and diammonium spacers, obtaining ‘dimeric’ molecules 3 and 4. The structure-based rational design of compounds 1-4 was guided by the optimization of MD-2 and CD14 binding. Compounds 1 and 2 inhibited TLR4 activation, in a concentration-dependent manner, and signaling in HEK-Blue TLR4 cells. The fluorescent labeling of murine macrophages by molecule 1 was inhibited by LPS and was also abrogated when cell surface proteins were digested by trypsin, thus suggesting an interaction of fluorescent probe 1 with membrane proteins of the TLR4 receptor system.
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- 2016
17. LATE-BREAKING ABSTRACT: Exploiting the ability of1H-NMR to differentiate patients with severe alpha-1-antitrypsin deficiency from controls based on metabolome profiling of exhaled breath condensate
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Fumagalli, M., primary, Stolk, Jan, additional, Ciaramelli, C., additional, Bussei, R., additional, Mazzoni, V., additional, Viglio, S., additional, Iadarola, Paolo, additional, and Airoldi, C., additional
- Published
- 2016
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18. Towards a universal approach based on omics technologies for the quality control of food
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Ferri, E, Galimberti, A, Casiraghi, M, Airoldi, C, Ciaramelli, C, Palmioli, A, Mezzasalma, V, Bruni, I, Labra, M, FERRI, EMANUELE, GALIMBERTI, ANDREA, CASIRAGHI, MAURIZIO, AIROLDI, CRISTINA, CIARAMELLI, CARLOTTA, PALMIOLI, ALESSANDRO, MEZZASALMA, VALERIO, BRUNI, ILARIA, LABRA, MASSIMO, Ferri, E, Galimberti, A, Casiraghi, M, Airoldi, C, Ciaramelli, C, Palmioli, A, Mezzasalma, V, Bruni, I, Labra, M, FERRI, EMANUELE, GALIMBERTI, ANDREA, CASIRAGHI, MAURIZIO, AIROLDI, CRISTINA, CIARAMELLI, CARLOTTA, PALMIOLI, ALESSANDRO, MEZZASALMA, VALERIO, BRUNI, ILARIA, and LABRA, MASSIMO
- Abstract
In the last decades, food science has greatly developed, turning from the consideration of food as mere source of energy to a growing awareness on its importance for health and particularly in reducing the risk of diseases. Such vision led to an increasing attention towards the origin and quality of raw materials as well as their derived food products. The continuous advance in molecular biology allowed setting up efficient and universal omics tools to unequivocally identify the origin of food items and their traceability. In this review, we considered the application of a genomics approach known as DNA barcoding in characterizing the composition of foodstuffs and its traceability along the food supply chain. Moreover, metabolomics analytical strategies based on Nuclear Magnetic Resonance (NMR) and Mass Spectroscopy (MS) were discussed as they also work well in evaluating food quality. The combination of both approaches allows us to define a sort of molecular labelling of food that is easily understandable by the operators involved in the food sector: producers, distributors, and consumers. Current technologies based on digital information systems such as web platforms and smartphone apps can facilitate the adoption of such molecular labelling.
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- 2015
19. Synthesis and characterization of new small-molecule ligands of LPS binding proteins.
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Ciaramelli, C, PERI, FRANCESCO, CIARAMELLI, CARLOTTA, Ciaramelli, C, PERI, FRANCESCO, and CIARAMELLI, CARLOTTA
- Abstract
Lo scopo del presente lavoro è la progettazione, la sintesi e la caratterizzazione di nuove small molecules, attive come ligandi di LPS (lipopolisaccaridi)-binding proteins. Gli LPS, o endotossine batteriche, sono macromolecole anfifiliche ubiquitarie sulla membrana esterna dei batteri Gram-negativi. Le proteine che legano gli LPS studiate nel corso di questo progetto di tesi di dottorato appartengono a due categorie: le proteine batteriche di trasporto Lpt e il sistema recettoriale TLR4, che comprende anche i co-recettori LBP, CD14, MD2. Le proteine Lpt, e in particolare la proteina LptC, sono responsabili del meccanismo di esportazione del LPS alla superficie cellulare, che è uno step fondamentale della via biosintetica dell’LPS. Pertanto, la biogenesi dell’LPS rappresenta un target ideale per lo sviluppo di nuovi antibiotici contro i batteri Gram-negativi. Inoltre, le strutture delle proteine Lpt sono state risolte, ma il meccanismo di trasporto è ancora da elucidare. Nel presente lavoro di tesi sono stati utilizzate diverse tecniche per studiare l'interazione tra LPS e LptC, con particolare attenzione agli studi di interazione via NMR. Inoltre, un nuovo LPS fluorescente è stato prodotto ed è stato utilizzato come tool per studi di interazione LPS-LptC con tecniche di fluorescenza. Sono state anche sviluppate alcune nuove molecole sintetiche. Questi glicolipidi sono stati progettati e sintetizzati per ottenere ligandi di LptC e, in prospettiva, potenziali antibiotici contro i batteri Gram-negativi. Il Toll-like receptor 4 (TLR4), il recettore dell'immunità innata, riconosce l’LPS aiutato da altre proteine (LBP, CD14 e MD-2) ed è responsabile dell'induzione della risposta infiammatoria. Molecole sintetiche in grado di modulare l'attività dei recettori dell’immunità innata sono un potente mezzo per studiare il sistema recettoriale TLR4 e hanno grande interesse farmacologico come adiuvanti vaccinali (agonisti), agenti antisepsi e anti-infiammatori (antagoni, The purpose of this work is the design, synthesis and characterization of new small molecules, active as ligands of two different lipopolysaccharide (LPS)-binding proteins. LPS, or bacterial endotoxin, is an amphiphilic macromolecule ubiquitous on the outer membrane of Gram-negative bacteria. The LPS binding proteins studied during this thesis project belong to two classes: the bacterial proteins of the Lpt transport machinery and the mammalian TLR4 receptor system, including the co-receptors LBP, CD14, MD-2. Lpt proteins, and in particular the protein LptC, are responsible for the export mechanism of LPS to the cell surface of Gram negative bacteria, which is a fundamental step of the LPS biosynthetic pathway. Therefore, the LPS biogenesis represents an ideal target for development of novel antibiotics against Gram-negative bacteria. Moreover, the structures of Lpt proteins have been elucidated, but very little is known about the mechanism of LPS transport. In this thesis work different techniques were used to study the interaction between LPS and LptC, particularly NMR binding studies. Moreover, a new fluorescent LPS was produced and it was used as a tool to perform LPS-LptC interaction studies with fluorescence techniques. Some new synthetic molecules were also developed during this thesis. Glycolipidic small molecules were designed and synthesized in order to obtain LptC ligands and, in perspective, potential antibiotics against Gram-negative bacteria. Toll-like receptor 4 (TLR4), the innate immunity receptor, recognizes LPS, helped by other proteins (LBP, CD14 and MD-2), and it is responsible for the induction of inflammatory responses. Synthetic small molecules able to modulate innate immunity receptors activity are a powerful mean to study the TLR4 receptor system and have great pharmacological interest as vaccine adjuvants (agonists), antisepsis and anti-inflammatory agents (antagonists). Antagonist activity on TLR4 receptor system of amino glycolipids (IAXO
- Published
- 2015
20. Modulation of CD14 and TLR4·MD-2 activities by a synthetic lipid A mimetic
- Author
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Cighetti, R, Ciaramelli, C, Sestito, S, Zanoni, I, Kubik, Ł, Ardá Freire, A, Calabrese, V, Granucci, F, Jerala, R, Martín Santamaría, S, Jiménez Barbero, J, Peri, F, CIGHETTI, ROBERTO, CIARAMELLI, CARLOTTA, SESTITO, STEFANIA ENZA, ZANONI, IVAN, CALABRESE, VALENTINA, GRANUCCI, FRANCESCA, PERI, FRANCESCO, Cighetti, R, Ciaramelli, C, Sestito, S, Zanoni, I, Kubik, Ł, Ardá Freire, A, Calabrese, V, Granucci, F, Jerala, R, Martín Santamaría, S, Jiménez Barbero, J, Peri, F, CIGHETTI, ROBERTO, CIARAMELLI, CARLOTTA, SESTITO, STEFANIA ENZA, ZANONI, IVAN, CALABRESE, VALENTINA, GRANUCCI, FRANCESCA, and PERI, FRANCESCO
- Abstract
Monosaccharide lipid A mimetics based on a glucosamine core linked to two fatty acid chains and bearing one or two phosphate groups have been synthesized. Compounds 1 and 2, each with one phosphate group, were practically inactive in inhibiting LPS-induced TLR4 signaling and cytokine production in HEK-blue cells and murine macrophages, but compound 3, with two phosphate groups, was found to be active in efficiently inhibiting TLR4 signal in both cell types. The direct interaction between compound 3 and the MD-2 coreceptor was investigated by NMR spectroscopy and molecular modeling/docking analysis. This compound also interacts directly with the CD14 receptor, stimulating its internalization by endocytosis. Experiments on macrophages show that the effect on CD14 reinforces the activity on MD-2·TLR4 because compound 3's activity is higher when CD14 is important for TLR4 signaling (i.e., at low LPS concentration). The dual targeting of MD-2 and CD14, accompanied by good solubility in water and lack of toxicity, suggests the use of monosaccharide 3 as a lead compound for the development of drugs directed against TLR4-related syndromes.
- Published
- 2014
21. Green and Roasted Coffee Extracts Inhibit Interferon-β Release in LPS-Stimulated Human Macrophages
- Author
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Valentina Artusa, Carlotta Ciaramelli, Alessia D’Aloia, Fabio Alessandro Facchini, Nicole Gotri, Antonino Bruno, Barbara Costa, Alessandro Palmioli, Cristina Airoldi, Francesco Peri, Artusa, V, Ciaramelli, C, D’Aloia, A, Facchini, F, Gotri, N, Bruno, A, Costa, B, Palmioli, A, Airoldi, C, and Peri, F
- Subjects
Pharmacology ,5-CQA ,chlorogenic acid ,coffee extracts ,immunomodulation ,inflammation ,interferon-β ,macrophages ,coffee extract ,Pharmacology (medical) ,macrophage - Abstract
The anti-inflammatory activity of coffee extracts is widely recognized and supported by experimental evidence, in both in vitro and in vivo settings, mainly murine models. Here, we investigated the immunomodulatory properties of coffee extracts from green (GCE) and medium-roasted (RCE) Coffea canephora beans in human macrophages. The biological effect of GCE and RCE was characterized in LPS-stimulated THP-1-derived human macrophages (TDM) as a model of inflammation. Results showed decreased amounts of TNF-α, IL-6 and IL-1β and a strong dose-dependent inhibition of interferon-β (IFN-β) release. Molecular mechanism of IFN-β inhibition was further investigated by immunofluorescence confocal microscopy analysis that showed a diminished nuclear translocation of p-IRF-3, the main transcription factor responsible for IFN-β synthesis. The inhibition of IFN-β release by RCE and GCE was also confirmed in human primary CD14+ monocytes-derived macrophages (MDM). The main component of coffee extracts, 5-O-caffeoylquinic acid (5-CQA) also inhibited IFN-β production, through a mechanism occurring downstream to TLR4. Inhibition of IFN-β release by coffee extracts parallels with the activity of their main phytochemical component, 5-CQA, thus suggesting that this compound is the main responsible for the immunomodulatory effect observed. The application of 5-CQA and coffee derived-phytoextracts to target interferonopathies and inflammation-related diseases could open new pharmacological and nutritional perspectives.
- Published
- 2022
22. NMR-Driven Identification of Cinnamon Bud and Bark Components With Anti-Aβ Activity
- Author
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Carlotta Ciaramelli, Alessandro Palmioli, Irene Angotti, Laura Colombo, Ada De Luigi, Gessica Sala, Mario Salmona, Cristina Airoldi, Ciaramelli, C, Palmioli, A, Angotti, I, Colombo, L, De Luigi, A, Sala, G, Salmona, M, and Airoldi, C
- Subjects
antioxidant ,CHIM/08 - CHIMICA FARMACEUTICA ,CHIM/01 - CHIMICA ANALITICA ,UPLC-HR-MS ,Aβ peptide ,CHIM/06 - CHIMICA ORGANICA ,General Chemistry ,anti-amiloidogenic compound ,Alzheimer’s disease ,cinnamon ,NMR metabolic profiling - Abstract
The anti-Alzheimer disease (AD) activity reported for an aqueous cinnamon bark extract prompted us to investigate and compare the anti-amyloidogenic properties of cinnamon extracts obtained from both bark and bud, the latter being a very little explored matrix. We prepared the extracts with different procedures (alcoholic, hydroalcoholic, or aqueous extractions). An efficient protocol for the rapid analysis of NMR spectra of cinnamon bud and bark extracts was set up, enabling the automatic identification and quantification of metabolites. Moreover, we exploited preparative reverse-phase (RP) chromatography to prepare fractions enriched in polyphenols, further characterized by UPLC-HR-MS. Then, we combined NMR-based molecular recognition studies, atomic force microscopy, and in vitro biochemical and cellular assays to investigate the anti-amyloidogenic activity of our extracts. Both bud and bark extracts showed a potent anti-amyloidogenic activity. Flavanols, particularly procyanidins, and cinnamaldehydes, are the chemical components of cinnamon hindering Aβ peptide on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line. Together with the previously reported ability to hinder tau aggregation and filament formation, these data indicate cinnamon polyphenols as natural products possessing multitarget anti-AD activity. Since cinnamon is a spice increasingly present in the human diet, our results support its use to prepare nutraceuticals useful in preventing AD through an active contrast to the biochemical processes that underlie the onset of this disease. Moreover, the structures of cinnamon components responsible for cinnamon anti-AD activities represent molecular templates for designing and synthesizing new anti-amyloidogenic drugs.
- Published
- 2022
23. Coffee variety, origin and extraction procedure: Implications for coffee beneficial effects on human health
- Author
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Cristina Airoldi, Carlotta Ciaramelli, Alessandro Palmioli, Ciaramelli, C, Palmioli, A, and Airoldi, C
- Subjects
Coffee origin ,Magnetic Resonance Spectroscopy ,Antioxidant ,Polymers ,medicine.medical_treatment ,Coffea ,Raw material ,Coffee ,01 natural sciences ,Antioxidants ,Analytical Chemistry ,Arabica and Robusta coffee ,Sonication ,chemistry.chemical_compound ,Human health ,Roasted coffee bean ,Alkaloids ,0404 agricultural biotechnology ,Nutraceutical ,CHIM/01 - CHIMICA ANALITICA ,Trigonelline ,Caffeine ,CHIM/06 - CHIMICA ORGANICA ,medicine ,Humans ,Food science ,Beneficial effects ,Principal Component Analysis ,Green coffee bean ,010401 analytical chemistry ,Melanoidin ,04 agricultural and veterinary sciences ,General Medicine ,CHIM/10 - CHIMICA DEGLI ALIMENTI ,040401 food science ,NMR metabolic profiling ,Antioxidant capacity ,0104 chemical sciences ,chemistry ,Seeds ,Chlorogenic Acid ,Food Science - Abstract
We set up an efficient protocol for the rapid analysis of NMR spectra of green and roasted coffee extracts, enabling the automatic identification and quantification of metabolites in approximately two minutes per spectrum. This method allowed for the metabolic profiling and the subsequent evaluation of the content of bioactive compounds and antioxidant activity of coffee samples, depending on their species (Arabica and Robusta), geographical origin and extraction procedure (hydroalcoholic, espresso and moka). The hydroalcoholic extraction is the most efficient method in terms of yields of low molecular weight compounds (in particular chlorogenic acids), while moka extraction provides the highest amounts of melanoidins. Moreover, that the ratio between health-giving compounds (chlorogenic acids, trigonelline and choline) and caffeine is higher in Arabica coffees. The data collected provide useful insights for the selection of coffee raw material to be used in the preparation of coffee-based dietary supplements, nutraceuticals and functional beverages.
- Published
- 2019
24. NMR-based Lavado cocoa chemical characterization and comparison with fermented cocoa varieties: insights on cocoa’s anti-amyloidogenic activity
- Author
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Alessandro Palmioli, Ada De Luigi, Cristina Airoldi, Gessica Sala, Laura Colombo, Carlotta Ciaramelli, Mario Salmona, Ciaramelli, C, Palmioli, A, De Luigi, A, Colombo, L, Sala, G, Salmona, M, and Airoldi, C
- Subjects
Magnetic Resonance Spectroscopy ,Metabolite ,01 natural sciences ,Antioxidants ,Analytical Chemistry ,Anti-amyloidogenic compound ,chemistry.chemical_compound ,Protein Aggregates ,0404 agricultural biotechnology ,NMR spectroscopy ,CHIM/01 - CHIMICA ANALITICA ,Cell Line, Tumor ,Aβ peptide ,CHIM/06 - CHIMICA ORGANICA ,medicine ,Humans ,Food science ,Theobromine ,Chromatography, High Pressure Liquid ,Cacao ,Chromatography, Reverse-Phase ,Amyloid beta-Peptides ,Chemistry ,Atomic force microscopy ,Plant Extracts ,010401 analytical chemistry ,Significant difference ,food and beverages ,04 agricultural and veterinary sciences ,General Medicine ,Nuclear magnetic resonance spectroscopy ,Alzheimer's disease ,CHIM/10 - CHIMICA DEGLI ALIMENTI ,040401 food science ,Peptide Fragments ,0104 chemical sciences ,Flavanones ,Lavado cocoa ,Fermentation ,Flavanol ,Fermented Foods ,Metabolic profile ,Food Science ,medicine.drug - Abstract
The metabolic profile of Lavado cocoa was characterized for the first time by NMR spectroscopy, then compared with the profiles of fermented and processed varieties, Natural and commercial cocoa. The significant difference in the contents of theobromine and flavanols prompted us to examine the various cocoa varieties to seek correlations between these metabolite concentrations and the anti-amyloidogenic activity reported for cocoa in the literature. We combined NMR spectroscopy, preparative reversed-phase (RP) chromatography, atomic force microscopy, in vitro biochemical and cell assays, to investigate and compare the anti-amyloidogenic properties of extracts and fractions enriched in different metabolite classes. Lavado variety was the most active and the catechins and theobromine were the chemical components of cocoa hindering Aβ peptide on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line.
- Published
- 2021
25. Metabolomic profiling of beers: Combining 1H NMR spectroscopy and chemometric approaches to discriminate craft and industrial products
- Author
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Carlotta Ciaramelli, Cristina Airoldi, Alessandro Palmioli, Diego Alberici, Palmioli, A, Alberici, D, Ciaramelli, C, and Airoldi, C
- Subjects
1h nmr spectroscopy ,Traceability ,Computer science ,business.industry ,Industrial production ,010401 analytical chemistry ,04 agricultural and veterinary sciences ,General Medicine ,CHIM/10 - CHIMICA DEGLI ALIMENTI ,040401 food science ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Counterfeit ,Craft ,Chemometrics ,0404 agricultural biotechnology ,Metabolomic profiling ,CHIM/01 - CHIMICA ANALITICA ,CHIM/06 - CHIMICA ORGANICA ,Brewing ,Biochemical engineering ,business ,Craft beerIndustrial beerFood metabolomicsNMR metabolic profilingChemometricsMultivariate statistical analysisPCAOPLS-DA ,Food Science - Abstract
The authentication and traceability of craft beers is an important issue for both beer consumers and producers. Reliable analytical methods able to identify and discriminate products are needed to protect the craft brew market against fraud and counterfeit. Here, 1H NMR analysis of 31 beer samples, differing for beer style and brewing method (craft or industrial) was combined with multivariate statistical analysis, following both an untargeted and a targeted approach. NMR-based analysis of beer samples was sped developing a specific protocol enabling the automatic identification and quantification of metabolites in approximately thirty seconds per spectrum. A clear discrimination was achieved by exploiting 1H NMR analysis and multivariate chemometric methods and the targeted approach identified the metabolites responsible for the segregation. Overall, this study reports an analytical approach addressing beer traceability and is the starting point for the development of a standardized protocol for the discrimination of industrial and craft beers.
- Published
- 2020
26. Green coffee extract enhances oxidative stress resistance and delays aging in Caenorhabditis elegans
- Author
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Carlotta Ciaramelli, Cristina Airoldi, Ivano De Noni, Milda Stuknytė, Loredana Amigoni, Maria Elena Regonesi, Alessandro Palmioli, Ilaria Bruni, Chiara Magoni, Amigoni, L, Stuknytė, M, Ciaramelli, C, Magoni, C, Bruni, I, De Noni, I, Airoldi, C, Regonesi, M, and Palmioli, A
- Subjects
0301 basic medicine ,Antioxidant ,medicine.medical_treatment ,media_common.quotation_subject ,Medicine (miscellaneous) ,Green coffee extract ,medicine.disease_cause ,01 natural sciences ,High resolution mass spectrometry ,03 medical and health sciences ,NMR spectroscopy ,Antioxidant activity ,CHIM/06 - CHIMICA ORGANICA ,medicine ,TX341-641 ,Healthy aging ,Caenorhabditis elegans ,Caenorhabditis elegan ,media_common ,Nutrition and Dietetics ,biology ,Chemistry ,Nutrition. Foods and food supply ,010401 analytical chemistry ,Longevity ,Chlorogenic acid ,Stress resistance ,biology.organism_classification ,BIO/10 - BIOCHIMICA ,0104 chemical sciences ,030104 developmental biology ,Biochemistry ,Polyphenol ,Chlorogenic acids ,Oxidative stress ,Food Science - Abstract
Nutritional factors play a pivotal role for healthy aging and longevity. This is related to the antioxidant properties of the molecules present in some foods. Due to the high content of polyphenols, Green Coffee Extract (GCE) is a powerful antioxidant. Nevertheless, little is known about its effect on aging. We demonstrated the benefic effects of GCE on stress resistance, fertility and adult mean lifespan using Caenorhabditis elegans as a model. The mean and maximum lifespan of worms treated with GCE increased significantly in a dose-dependent manner, and animals pre-treated were more resistant to oxidative stress. NMR and UPLC/ESI-HRMS analyses of GCE confirmed a significant content of chlorogenic acids, being 5-O-caffeoylquinic acid (5-CQA) the most abundant isomer. The major activity demonstrated by GCE in comparison to the pure 5-CQA on C. elegans phenotypes clearly demonstrated the importance of the employment of a natural extract to develop functional foods and supplements.
- Published
- 2017
27. Nuclear Magnetic Resonance as an Attractive Resource for Monitoring Surveillance Candidates of Acute and Chronic Lung Disorders
- Author
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Cristina Airoldi, Carlotta Ciaramelli, Simona Viglio, Paolo Iadarola, Viglio, S, Airoldi, C, Ciaramelli, C, and Iadarola, P
- Subjects
Lung Disorder ,Resource (biology) ,business.industry ,Statistical analyses ,CHIM/06 - CHIMICA ORGANICA ,Medicine ,business ,Bioinformatics ,Nuclear Magnetic Resonance, Pulmonary Disorders, Metabolic Profiles, Metabolic Pathways, Statistical Analyses, Profile Comparison, Upregulation, Down-regulation, Amino Acids, Nucleosides, Nucleotides, Ketoacids, Krebs Cycle Intermediates ,Pulmonary disorders - Abstract
Metabolomics is the comprehensive study of metabolites, i.e. substrates and end-products of cell metabolism. These are low-molecular weight molecules which include amino, nucleic and organic acids, peptides, carbohydrates, vitamins, polyphenols, alkaloids and inorganic species. Being metabolite concentration influenced by both genetic and environmental factors, their amount directly reflects the underlying biochemical activity and state of cells, tissues or organisms. Profiling the metabolome could thus represent the molecular phenotype better than other approaches such as genomics and proteomics. Among the available procedures (Gas Chromatography-/Liquid Chromatography-Mass Spectrometry), high-resolution nuclear magnetic resonance spectroscopy (HR-NMR) is currently one of the leading analytical tools for metabolomic research due to its peculiarities. The distinctive advantage of NMR over other methods is the possibility to perform an inherent quantitative and untargeted analysis, also with respect to the chemical nature of metabolites. In addition, NMR shows a good reproducibility, a rapid acquisition time of spectra, and it is not destructive with regard to the sample for which little or no preparation is required. Taken together, these features have promoted NMR-assisted metabolomics to the rank of a valuable method for an efficient investigation of a variety of lung diseases. s S sAim of this chapter is to provide an overview of the applications of metabolomics to the study of acute and chronic lung disorders. Why focus on pulmonary disorders? First, by involving tens of million people, lung diseases are some of the most common medical conditions in the world. Second, the depth of analysis ultimately reached by current metabolomic procedures has provided a new and larger context for future studies on the biology of these conditions. This has allowed for the generation of metabolite profiles that could be useful for exploring pathological mechanisms and/or discovering new potential therapeutic targets for a variety of pulmonary disorders.
- Published
- 2019
28. Glycan Carriers As Glycotools for Medicinal Chemistry Applications
- Author
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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
- Subjects
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.
- Published
- 2018
29. Structure-Activity Relationship in Monosaccharide-Based Toll-Like Receptor 4 (TLR4) Antagonists
- Author
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Sonsoles Martín-Santamaría, Rudi Beyaert, Andra B Schromm, Lenny Zaffaroni, Cristina Airoldi, Fabio A. Facchini, Silvia Rapisarda, Grisha Pirianov, Carlotta Ciaramelli, Matilde Forcella, Paola Fusi, Roman Jerala, Alberto Minotti, Jean-Marc Billod, Valentina Calabrese, Charys Palmer, Fabio Lapenta, Francesco Peri, Harald Braun, Facchini, F, Zaffaroni, L, Minotti, A, Rapisarda, S, Calabrese, V, Forcella, M, Fusi, P, Airoldi, C, Ciaramelli, C, Billod, J, Schromm, A, Braun, H, Palmer, C, Beyaert, R, Lapenta, F, Jerala, R, Pirianov, G, Martin-Santamaria, S, and Peri, F
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Models, Molecular ,Molecular model ,LIPOPOLYSACCHARIDE RECOGNITION ,Molecular Conformation ,PROTEIN ,Ligands ,ACTIVATION ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Glucosamine ,CHIM/06 - CHIMICA ORGANICA ,Drug Discovery ,Medicine and Health Sciences ,N-LINKED GLYCOSYLATIONS ,chemistry.chemical_classification ,TLR4, MD-2, glycolipids, SAR ,BIOACTIVITY ,Fatty Acids ,Monosaccharides ,Biological activity ,Recombinant Proteins ,3. Good health ,Molecular Docking Simulation ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Signal Transduction ,Stereochemistry ,Molecular Dynamics Simulation ,Binding, Competitive ,Cell Line ,03 medical and health sciences ,Structure-Activity Relationship ,Molecule ,Monosaccharide ,Structure–activity relationship ,Animals ,Humans ,ddc:610 ,CELL ,Interleukin-8 ,Antagonist ,Fatty acid ,Biology and Life Sciences ,SEVERE SEPSIS ,Toll-Like Receptor 4 ,030104 developmental biology ,HEK293 Cells ,CHIM/08 - CHIMICA FARMACEUTICA ,chemistry ,MD-2 ,ENDOTOXIN ,LIPID-A ANALOGS ,BIOLOGICAL-ACTIVITY ,030215 immunology - Abstract
The structure-activity relationship was investigated in a series of synthetic TLR4 antagonists formed by a glucosamine core linked to two phosphate esters and two linear carbon chains. Molecular modeling showed that the compounds with 10, 12, and 14 carbons chains are associated with higher stabilization of the MD-2/TLR4 antagonist conformation than in the case of the C16 variant. Binding experiments with human MD-2 showed that the C12 and C14 variants have higher affinity than C10, while the C16 variant did not interact with the protein. The molecules, with the exception of the C16 variant, inhibited the LPS-stimulated TLR4 signal in human and murine cells, and the antagonist potency mirrored the MD-2 affinity calculated from in vitro binding experiments. Fourier-transform infrared, nuclear magnetic resonance, and small angle X-ray scattering measurements suggested that the aggregation state in aqueous solution depends on fatty acid chain lengths and that this property can influence TLR4 activity in this series of compounds.
- Published
- 2018
30. NMR-driven identification of anti-amyloidogenic compounds in green and roasted coffee extracts
- Author
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Chiara Zoia, Laura Colombo, Gessica Sala, Carlotta Ciaramelli, Cristina Airoldi, Alessandro Palmioli, Chiara Riva, Ada De Luigi, Mario Salmona, Ciaramelli, C, Palmioli, A, De Luigi, A, Colombo, L, Sala, G, Riva, C, Zoia, C, Salmona, M, and Airoldi, C
- Subjects
Magnetic Resonance Spectroscopy ,Food Handling ,Coffee, 5-CQA ,Cell ,Color ,Food chemistry ,010402 general chemistry ,01 natural sciences ,Coffee ,Analytical Chemistry ,Anti-amyloidogenic compound ,chemistry.chemical_compound ,NMR spectroscopy ,Cell Line, Tumor ,Aβ peptide ,CHIM/06 - CHIMICA ORGANICA ,medicine ,Humans ,Cytotoxicity ,Hydrogen peroxide ,Amyloid beta-Peptides ,010405 organic chemistry ,Chemistry ,Atomic force microscopy ,Plant Extracts ,Melanoidin ,General Medicine ,Nuclear magnetic resonance spectroscopy ,In vitro ,0104 chemical sciences ,medicine.anatomical_structure ,Biochemistry ,Cell culture ,Protein Multimerization ,Alzheimer’s disease ,Food Science - Abstract
To identify food and beverages that provide the regular intake of natural compounds capable of interfering with toxic amyloidogenic aggregates, we developed an experimental protocol that combines NMR spectroscopy and atomic force microscopy, in vitro biochemical and cell assays to detect anti-Aβ molecules in natural edible matrices. We applied this approach to investigate the potential anti-amyloidogenic properties of coffee and its molecular constituents. Our data showed that green and roasted coffee extracts and their main components, 5-O-caffeoylquinic acid and melanoidins, can hinder Aβ on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line. Coffee extracts and melanoidins also counteract hydrogen peroxide- and rotenone-induced cytotoxicity and modulate some autophagic pathways in the same cell line.
- Published
- 2018
31. Towards a Universal Approach Based on Omics Technologies for the Quality Control of Food
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Massimo Labra, Alessandro Palmioli, Cristina Airoldi, Valerio Mezzasalma, Carlotta Ciaramelli, Emanuele Ferri, Andrea Galimberti, Maurizio Casiraghi, Ilaria Bruni, Ferri, E, Galimberti, A, Casiraghi, M, Airoldi, C, Ciaramelli, C, Palmioli, A, Mezzasalma, V, Bruni, I, and Labra, M
- Subjects
Quality Control ,Magnetic Resonance Spectroscopy ,Traceability ,Immunology and Microbiology (all) ,media_common.quotation_subject ,Control (management) ,lcsh:Medicine ,Review Article ,Biology ,Mass Spectrometry ,General Biochemistry, Genetics and Molecular Biology ,Information system ,DNA Barcoding, Taxonomic ,Humans ,Metabolomics ,Quality (business) ,media_common ,Biochemistry, Genetics and Molecular Biology (all) ,General Immunology and Microbiology ,business.industry ,lcsh:R ,digestive, oral, and skin physiology ,General Medicine ,Data science ,Food Analysis ,Biotechnology ,Smartphone app ,business ,Food quality ,Omics technologies - Abstract
In the last decades, food science has greatly developed, turning from the consideration of food as mere source of energy to a growing awareness on its importance for health and particularly in reducing the risk of diseases. Such vision led to an increasing attention towards the origin and quality of raw materials as well as their derived food products. The continuous advance in molecular biology allowed setting up efficient and universal omics tools to unequivocally identify the origin of food items and their traceability. In this review, we considered the application of a genomics approach known as DNA barcoding in characterizing the composition of foodstuffs and its traceability along the food supply chain. Moreover, metabolomics analytical strategies based on Nuclear Magnetic Resonance (NMR) and Mass Spectroscopy (MS) were discussed as they also work well in evaluating food quality. The combination of both approaches allows us to define a sort of molecular labelling of food that is easily understandable by the operators involved in the food sector: producers, distributors, and consumers. Current technologies based on digital information systems such as web platforms and smartphone apps can facilitate the adoption of such molecular labelling.
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- 2015
32. Flavonoids in the Treatment of Alzheimer's and Other Neurodegenerative Diseases
- Author
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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
- Subjects
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.
- Published
- 2017
33. Campo, rete e produzione di soggettività. Foucault all'origine della virata psicoanalitica di Bourdieu?
- Author
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BRINDISI, Gianvito, A. Abruzzese, G. Alfano, L. Bazzicalupo, R. Bonito Oliva, M. Bottone, G. Brindisi, G. Cantillo, F. Ciaramelli, C. Colangelo, V. Cuomo, E. de Conciliis, M. Fimiani, A. Giugliano, E. Mazzarella, F.C. Papparo, S. Prinzi, D. Tarizzo, M. Zanardi, C. Colangelo, V. Cuomo, F.C. Papparo, and Brindisi, Gianvito
- Subjects
Michel Foucault, Pierre Bourdieu, Potere, Soggettività, Psicoanalisi - Published
- 2017
34. H-1 NMR To Explore the Metabolome of Exhaled Breath Condensate in alpha(1)-Antitrypsin Deficient Patients: A Pilot Study
- Author
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Marco Fumagalli, Valeria Mazzoni, Carlotta Ciaramelli, Rita Bussei, Simona Viglio, Paolo Iadarola, Cristina Airoldi, Jan Stolk, Airoldi, C, Ciaramelli, C, Fumagalli, M, Bussei, R, Mazzoni, V, Viglio, S, Iadarola, P, and Stolk, J
- Subjects
0301 basic medicine ,exhaled breath condensate ,medicine.medical_specialty ,Metabolite ,α1-antitrypsin COPD ,Biochemistry ,Gastroenterology ,alpha 1-antitrypsin COPD ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolomics ,Internal medicine ,CHIM/06 - CHIMICA ORGANICA ,medicine ,Metabolome ,Exhaled breath condensate ,Alpha 1-antitrypsin deficiency ,NMR-based metabolomic ,Case-control study ,Exhalation ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,medicine.disease ,030104 developmental biology ,chemistry ,NMR-based metabolomics - Abstract
The metabolomic analysis of exhaled breath condensate (EBC) may provide insights on both the pathology of pulmonary disorders and the response to therapy. This pilot study describes the ability of nuclear magnetic resonance (NMR)-based metabolomics to discriminate α1-antitrypsin deficient (AATD)-patients, who were diagnosed with moderate to severe emphysema, from healthy individuals. Comparative analysis of samples from these two homogeneous cohorts of individuals resulted in the generation of NMR profiles that were different from both a qualitative and a quantitative point-of-view. Among the identified metabolites that separated patients from controls, acetoin, propionate, acetate, and propane-1,2 diol were those presenting the biggest difference. Unambiguous confirmation that the two groups could be completely differentiated on the basis of their metabolite content came from the application of univariate and multivariate statistical analysis (principal component analysis, partial least squares discriminant analysis (PLS-DA), and orthogonal PLS-DA). MetaboAnalyst 3.0 platform, used to define a relationship among metabolites, allowed us to observe that pyruvate metabolism is the most-involved pathway, most of metabolites being originated from pyruvate. These preliminary data suggest that NMR, with its ability to differentiate the metabolic fingerprint of EBC of AATD patients from that of healthy controls, has a potential "clinical applicability" in this area.
- Published
- 2016
35. Glycolipid-based TLR4 Modulators and Fluorescent Probes: Rational Design, Synthesis, and Biological Properties
- Author
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Stefania E. Sestito, Matteo Piazza, Roman Jerala, Javier Klett, Carlotta Ciaramelli, Sonsoles Martín-Santamaría, Francesco Peri, Valentina Calabrese, Alja Oblak, Lucia Perez-Regidor, Ciaramelli, C, Calabrese, V, Sestito, S, Pérez Regidor, L, Klett, J, Oblak, A, Jerala, R, Piazza, M, Martín Santamaría, S, and Peri, F
- Subjects
0301 basic medicine ,Receptor complex ,Fluorescent Dye ,Glycolipid ,Biology ,Biochemistry ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicinal chemistry ,Drug Discovery ,CHIM/06 - CHIMICA ORGANICA ,medicine ,fluorescent chemical probe ,Animals ,Humans ,TLR4 ,Receptor ,Fluorescent Dyes ,Pharmacology ,Animal ,Organic Chemistry ,Rational design ,antagonist ,Trypsin ,Fluorescence ,computational chemistry ,Toll-Like Receptor 4 ,030104 developmental biology ,Membrane ,Membrane protein ,MD-2 ,Drug Design ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Glycolipids ,HEK-TLR4 cell ,030217 neurology & neurosurgery ,medicine.drug ,Human - Abstract
The cationic glycolipid IAXO-102, a potent TLR4 antagonist targeting both MD-2 and CD14 co-receptors, has been used as scaffold to design new potential TLR4 modulators and fluorescent labels for the TLR4 receptor complex (membrane TLR4.MD-2 dimer and CD14). The primary amino group of IAXO-102, not involved in direct interaction with MD-2 and CD14 receptors, has been exploited to covalently attach a fluorescein (molecules 1 and 2) or to link two molecules of IAXO-102 through diamine and diammonium spacers, obtaining 'dimeric' molecules 3 and 4. The structure-based rational design of compounds 1-4 was guided by the optimization of MD-2 and CD14 binding. Compounds 1 and 2 inhibited TLR4 activation, in a concentration-dependent manner, and signaling in HEK-Blue TLR4 cells. The fluorescent labeling of murine macrophages by molecule 1 was inhibited by LPS and was also abrogated when cell surface proteins were digested by trypsin, thus suggesting an interaction of fluorescent probe 1 with membrane proteins of the TLR4 receptor system.
- Published
- 2015
36. Synthesis and characterization of new small-molecule ligands of LPS binding proteins
- Author
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CIARAMELLI, CARLOTTA, Ciaramelli, C, and PERI, FRANCESCO
- Subjects
CHIM/06 - CHIMICA ORGANICA ,LPS, medicinal chemistry, drug design, carbohydrates, innate immunity, TLR4, NMR, LptC, ligand design, antibiotics - Abstract
Lo scopo del presente lavoro è la progettazione, la sintesi e la caratterizzazione di nuove small molecules, attive come ligandi di LPS (lipopolisaccaridi)-binding proteins. Gli LPS, o endotossine batteriche, sono macromolecole anfifiliche ubiquitarie sulla membrana esterna dei batteri Gram-negativi. Le proteine che legano gli LPS studiate nel corso di questo progetto di tesi di dottorato appartengono a due categorie: le proteine batteriche di trasporto Lpt e il sistema recettoriale TLR4, che comprende anche i co-recettori LBP, CD14, MD2. Le proteine Lpt, e in particolare la proteina LptC, sono responsabili del meccanismo di esportazione del LPS alla superficie cellulare, che è uno step fondamentale della via biosintetica dell’LPS. Pertanto, la biogenesi dell’LPS rappresenta un target ideale per lo sviluppo di nuovi antibiotici contro i batteri Gram-negativi. Inoltre, le strutture delle proteine Lpt sono state risolte, ma il meccanismo di trasporto è ancora da elucidare. Nel presente lavoro di tesi sono stati utilizzate diverse tecniche per studiare l'interazione tra LPS e LptC, con particolare attenzione agli studi di interazione via NMR. Inoltre, un nuovo LPS fluorescente è stato prodotto ed è stato utilizzato come tool per studi di interazione LPS-LptC con tecniche di fluorescenza. Sono state anche sviluppate alcune nuove molecole sintetiche. Questi glicolipidi sono stati progettati e sintetizzati per ottenere ligandi di LptC e, in prospettiva, potenziali antibiotici contro i batteri Gram-negativi. Il Toll-like receptor 4 (TLR4), il recettore dell'immunità innata, riconosce l’LPS aiutato da altre proteine (LBP, CD14 e MD-2) ed è responsabile dell'induzione della risposta infiammatoria. Molecole sintetiche in grado di modulare l'attività dei recettori dell’immunità innata sono un potente mezzo per studiare il sistema recettoriale TLR4 e hanno grande interesse farmacologico come adiuvanti vaccinali (agonisti), agenti antisepsi e anti-infiammatori (antagonisti). L’attività biologica di glicolipidi con una funzione amminica (IAXO-102) come antagonisti del TLR4 è stata chiaramente dimostrata dal nostro gruppo di ricerca. La sintesi di molecole derivate da IAXO-102, che mantengano l'attività biologica del precursore, è stato un obiettivo di questo lavoro. In particolare, sono state portate a termine le sintesi di sonde fluorescenti, utilizzate per studi di interazione, derivati zwitterionici e molecole dimeriche. Nei nostri laboratori sono stati ottenuti anche antagonisti anionici del TLR4 con una struttura chimica più simile a Lipide A. Lo scopo di questo lavoro è stato valutare, tramite esperimenti NMR, la loro capacità di legare co-recettore dell'immunità innata MD-2. Il carattere anfifilico degli analoghi sintetici del lipide A sintetizzati finora è spesso associato ad una bassa solubilità in acqua e a scarsa biodisponibilità. Invece, i composti attivi sul TLR4 di origine naturale hanno una migliore solubilità e biodisponibilità. La modifica chimica di queste strutture è molto utile per modulare l'attività biologica e per migliorare la specificità nei confronti del target. Di conseguenza, in una fase successiva di questo lavoro di tesi, è stata intrapresa la sintesi di nuove molecole con strutture chimiche ispirate ai modulatori naturali del TLR4. Recentemente è stato dimostrato che alcuni composti fenolici estratti da olio di oliva hanno una buona attività come antagonisti del TLR4. Pertanto, la sintesi di alcuni analoghi di queste molecole è stata eseguita per ottenere nuovi potenziali antagonisti del TLR4, con una migliore solubilità in acqua e una ridotta tossicità. The purpose of this work is the design, synthesis and characterization of new small molecules, active as ligands of two different lipopolysaccharide (LPS)-binding proteins. LPS, or bacterial endotoxin, is an amphiphilic macromolecule ubiquitous on the outer membrane of Gram-negative bacteria. The LPS binding proteins studied during this thesis project belong to two classes: the bacterial proteins of the Lpt transport machinery and the mammalian TLR4 receptor system, including the co-receptors LBP, CD14, MD-2. Lpt proteins, and in particular the protein LptC, are responsible for the export mechanism of LPS to the cell surface of Gram negative bacteria, which is a fundamental step of the LPS biosynthetic pathway. Therefore, the LPS biogenesis represents an ideal target for development of novel antibiotics against Gram-negative bacteria. Moreover, the structures of Lpt proteins have been elucidated, but very little is known about the mechanism of LPS transport. In this thesis work different techniques were used to study the interaction between LPS and LptC, particularly NMR binding studies. Moreover, a new fluorescent LPS was produced and it was used as a tool to perform LPS-LptC interaction studies with fluorescence techniques. Some new synthetic molecules were also developed during this thesis. Glycolipidic small molecules were designed and synthesized in order to obtain LptC ligands and, in perspective, potential antibiotics against Gram-negative bacteria. Toll-like receptor 4 (TLR4), the innate immunity receptor, recognizes LPS, helped by other proteins (LBP, CD14 and MD-2), and it is responsible for the induction of inflammatory responses. Synthetic small molecules able to modulate innate immunity receptors activity are a powerful mean to study the TLR4 receptor system and have great pharmacological interest as vaccine adjuvants (agonists), antisepsis and anti-inflammatory agents (antagonists). Antagonist activity on TLR4 receptor system of amino glycolipids (IAXO-102) was clearly demonstrated by our research group. The synthesis of molecules derived from IAXO-102 which retain the biological activity of the precursor was a target of this work. In particular, the synthesis of fluorescent probes, used for binding studies, zwitterionic derivatives and dimeric molecules were performed. Anionic TLR4 antagonists with a chemical structure more similar to Lipid A were also obtained in our labs. The aim of this work was the evaluation via NMR binding experiments of their ability to bind the innate immunity co-receptor MD-2. The amphiphilic character of the synthetic lipid A analogues synthesized so far is often associated with low water solubility and poor bioavailability. In this respect, the natural TLR4-active compounds have better solubility and bioavailability. The chemical modification of these structures is very helpful to modulate their biological activity and to enhance target specificity. Consequently, in a later stage of this work, the synthesis of new small molecules with chemical structures inspired to natural TLR4 modulators was pursued. Very recently it was found that some phenolic compounds from olive oil extracts presented a good activity as TLR4 antagonists. The synthesis of some analogues of these molecules was performed to obtain new potential TLR4 antagonists with better water solubility and reduced toxicity.
- Published
- 2015
37. Functional characterization of E. coli LptC: Interaction with LPS and a synthetic ligand
- Author
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Luca Zambelloni, Alessandra Polissi, Valentina Calabrese, Carlotta Ciaramelli, Paola Sperandeo, Carlo Santambrogio, Rita Grandori, Stefania E. Sestito, G. Enrico Rovati, Francesco Peri, Sestito, S, Sperandeo, P, Santambrogio, C, Ciaramelli, C, Calabrese, V, Rovati, G, Zambelloni, L, Grandori, R, Polissi, A, and Peri, F
- Subjects
Lipopolysaccharides ,ligand design ,Models, Molecular ,LPS ,Fluorescent Dye ,Oligosaccharides ,Flos ,Lipopolysaccharide ,LptC ,Biochemistry ,Fluorescence ,Oligosaccharide ,Lipopolysaccharide transport ,Glycolipid ,antibiotic ,medicinal chemistry ,Escherichia coli Protein ,Escherichia coli ,Inner membrane ,Membrane Protein ,Molecular Biology ,Fluorescent Dyes ,biology ,Chemistry ,Escherichia coli Proteins ,Organic Chemistry ,Membrane Proteins ,Biological Transport ,Periplasmic space ,Ligand (biochemistry) ,biology.organism_classification ,Membrane protein ,Molecular Medicine ,Bacterial outer membrane - Abstract
Lipopolysaccharide (LPS), the main cell-surface molecular constituent of Gram-negative bacteria, is synthesized in the inner membrane (IM) and transported to the outer membrane (OM) by the Lpt (lipopolysaccharide transport) machinery. Neosynthesized LPS is first flipped by MsbA across the IM, then transported to the OM by seven Lpt proteins located in the IM (LptBCFG), in the periplasm (LptA), and in the OM (LptDE). A functional OM is essential to bacterial viability and requires correct placement of LPS in the outer leaflet. Therefore, LPS biogenesis represents an ideal target for the development of novel antibiotics against Gram-negative bacteria. Although the structures of Lpt proteins have been elucidated, little is known about the mechanism of LPS transport, and few data are available on Lpt-LPS binding. We report here the first determination of the thermodynamic and kinetic parameters of the interaction between LptC and a fluorescent lipo-oligosaccharide (fLOS) in vitro. The apparent dissociation constant (Kd) of the fLOS-LptC interaction was evaluated by two independent methods. The first was based on fLOS capture by resin-immobilized LptC; the second used quenching of LptC intrinsic fluorescence by fLOS in solution. The Kd values by the two methods (71.4 and 28.8 μm, respectively) are very similar, and are of the same order of magnitude as that of the affinity of LOS for the upstream transporter, MsbA. Interestingly, both methods showed that fLOS binding to LptC is mostly irreversible, thus reflecting the fact that LPS can be released from LptC only when energy is supplied by ATP or in the presence of a higher-affinity LptA protein. A fluorescent glycolipid was synthesized: this also interacted irreversibly with LptC, but with lower affinity (apparent Kd=221 μM). This compound binds LptC at the LPS binding site and is a prototype for the development of new antibiotics targeting LPS transport in Gram-negative bacteria. Towards a new generation of antibiotics: Enzymes of the Lpt family convey essential lipopolysaccharides (LPSs) to the outer membrane of Gram-negative bacteria, and hence are a promising target for novel antibiotics. Using a fluorescent conjugate, we have investigated the kinetics of the interaction between LPS and LptC. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
- Published
- 2014
38. Corrigendum to "The role of posterior parietal cortex and medial prefrontal cortex in distraction and mind-wandering" [Neuropsychologia 188 (2023) 108639].
- Author
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L GG, A C, G C, A A, and E C
- Published
- 2024
- Full Text
- View/download PDF
39. Cell-Free and In Vivo Characterization of the Inhibitory Activity of Lavado Cocoa Flavanols on the Amyloid Protein Ataxin-3: Toward New Approaches against Spinocerebellar Ataxia Type 3.
- Author
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Sciandrone B, Palmioli A, Ciaramelli C, Pensotti R, Colombo L, Regonesi ME, and Airoldi C
- Subjects
- Animals, Ataxin-3 genetics, Ataxin-3 metabolism, Amyloidogenic Proteins metabolism, Amyloid metabolism, Caenorhabditis elegans, Polyphenols therapeutic use, Plant Extracts pharmacology, Machado-Joseph Disease drug therapy, Machado-Joseph Disease genetics, Machado-Joseph Disease metabolism
- Abstract
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder characterized by ataxia and other neurological manifestations, with a poor prognosis and a lack of effective therapies. The amyloid aggregation of the ataxin-3 protein is a hallmark of SCA3 and one of the main biochemical events prompting its onset, making it a prominent target for the development of preventive and therapeutic interventions. Here, we tested the efficacy of an aqueous Lavado cocoa extract and its polyphenolic components against ataxin-3 aggregation and neurotoxicity. The combination of biochemical assays and atomic force microscopy morphological analysis provided clear evidence of cocoa flavanols' ability to hinder ATX3 amyloid aggregation through direct physical interaction, as assessed by NMR spectroscopy. The chemical identity of the flavanols was investigated by ultraperformance liquid chromatography-high-resolution mass spectrometry. The use of the preclinical model Caenorhabditis elegans allowed us to demonstrate cocoa flavanols' ability to ameliorate ataxic phenotypes in vivo. To the best of our knowledge, Lavado cocoa is the first natural source whose extract is able to directly interfere with ATX3 aggregation, leading to the formation of off-pathway species.
- Published
- 2024
- Full Text
- View/download PDF
40. Antarctic Soil Metabolomics: A Pilot Study.
- Author
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Ciaramelli C, Palmioli A, Brioschi M, Viglio S, D'Amato M, Iadarola P, Tosi S, Zucconi L, and Airoldi C
- Subjects
- Antarctic Regions, Pilot Projects, Chromatography, Liquid, Metabolomics methods, Soil chemistry, Tandem Mass Spectrometry
- Abstract
In Antarctica, ice-free areas can be found along the coast, on mountain peaks, and in the McMurdo Dry Valleys, where microorganisms well-adapted to harsh conditions can survive and reproduce. Metabolic analyses can shed light on the survival mechanisms of Antarctic soil communities from both coastal sites, under different plant coverage stages, and inner sites where slow-growing or dormant microorganisms, low water availability, salt accumulation, and a limited number of primary producers make metabolomic profiling difficult. Here, we report, for the first time, an efficient protocol for the extraction and the metabolic profiling of Antarctic soils based on the combination of NMR spectroscopy and mass spectrometry (MS). This approach was set up on samples harvested along different localities of Victoria Land, in continental Antarctica, devoid of or covered by differently developed biological crusts. NMR allowed for the identification of thirty metabolites (mainly sugars, amino acids, and organic acids) and the quantification of just over twenty of them. UPLC-MS analysis identified more than twenty other metabolites, in particular flavonoids, medium- and long-chain fatty acids, benzoic acid derivatives, anthracenes, and quinones. Our results highlighted the complementarity of the two analytical techniques. Moreover, we demonstrated that their combined use represents the "gold standard" for the qualitative and quantitative analysis of little-explored samples, such as those collected from Antarctic soils.
- Published
- 2023
- Full Text
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41. NMR-Driven Identification of Cinnamon Bud and Bark Components With Anti-Aβ Activity.
- Author
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Ciaramelli C, Palmioli A, Angotti I, Colombo L, De Luigi A, Sala G, Salmona M, and Airoldi C
- Abstract
The anti-Alzheimer disease (AD) activity reported for an aqueous cinnamon bark extract prompted us to investigate and compare the anti-amyloidogenic properties of cinnamon extracts obtained from both bark and bud, the latter being a very little explored matrix. We prepared the extracts with different procedures (alcoholic, hydroalcoholic, or aqueous extractions). An efficient protocol for the rapid analysis of NMR spectra of cinnamon bud and bark extracts was set up, enabling the automatic identification and quantification of metabolites. Moreover, we exploited preparative reverse-phase (RP) chromatography to prepare fractions enriched in polyphenols, further characterized by UPLC-HR-MS. Then, we combined NMR-based molecular recognition studies, atomic force microscopy, and in vitro biochemical and cellular assays to investigate the anti-amyloidogenic activity of our extracts. Both bud and bark extracts showed a potent anti-amyloidogenic activity. Flavanols, particularly procyanidins, and cinnamaldehydes, are the chemical components of cinnamon hindering Aβ peptide on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line. Together with the previously reported ability to hinder tau aggregation and filament formation, these data indicate cinnamon polyphenols as natural products possessing multitarget anti-AD activity. Since cinnamon is a spice increasingly present in the human diet, our results support its use to prepare nutraceuticals useful in preventing AD through an active contrast to the biochemical processes that underlie the onset of this disease. Moreover, the structures of cinnamon components responsible for cinnamon anti-AD activities represent molecular templates for designing and synthesizing new anti-amyloidogenic drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ciaramelli, Palmioli, Angotti, Colombo, De Luigi, Sala, Salmona and Airoldi.)
- Published
- 2022
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42. Green and Roasted Coffee Extracts Inhibit Interferon-β Release in LPS-Stimulated Human Macrophages.
- Author
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Artusa V, Ciaramelli C, D'Aloia A, Facchini FA, Gotri N, Bruno A, Costa B, Palmioli A, Airoldi C, and Peri F
- Abstract
The anti-inflammatory activity of coffee extracts is widely recognized and supported by experimental evidence, in both in vitro and in vivo settings, mainly murine models. Here, we investigated the immunomodulatory properties of coffee extracts from green (GCE) and medium-roasted (RCE) Coffea canephora beans in human macrophages. The biological effect of GCE and RCE was characterized in LPS-stimulated THP-1-derived human macrophages (TDM) as a model of inflammation. Results showed decreased amounts of TNF-α, IL-6 and IL-1β and a strong dose-dependent inhibition of interferon-β (IFN-β) release. Molecular mechanism of IFN-β inhibition was further investigated by immunofluorescence confocal microscopy analysis that showed a diminished nuclear translocation of p-IRF-3, the main transcription factor responsible for IFN-β synthesis. The inhibition of IFN-β release by RCE and GCE was also confirmed in human primary CD14
+ monocytes-derived macrophages (MDM). The main component of coffee extracts, 5- O -caffeoylquinic acid (5-CQA) also inhibited IFN-β production, through a mechanism occurring downstream to TLR4. Inhibition of IFN-β release by coffee extracts parallels with the activity of their main phytochemical component, 5-CQA, thus suggesting that this compound is the main responsible for the immunomodulatory effect observed. The application of 5-CQA and coffee derived-phytoextracts to target interferonopathies and inflammation-related diseases could open new pharmacological and nutritional perspectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Artusa, Ciaramelli, D’Aloia, Facchini, Gotri, Bruno, Costa, Palmioli, Airoldi and Peri.)- Published
- 2022
- Full Text
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43. NMR-based Lavado cocoa chemical characterization and comparison with fermented cocoa varieties: Insights on cocoa's anti-amyloidogenic activity.
- Author
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Ciaramelli C, Palmioli A, De Luigi A, Colombo L, Sala G, Salmona M, and Airoldi C
- Subjects
- Amyloid beta-Peptides chemistry, Amyloid beta-Peptides metabolism, Antioxidants chemistry, Cacao metabolism, Cell Line, Tumor, Chromatography, High Pressure Liquid, Chromatography, Reverse-Phase, Flavanones analysis, Humans, Magnetic Resonance Spectroscopy, Peptide Fragments chemistry, Peptide Fragments metabolism, Plant Extracts chemistry, Plant Extracts pharmacology, Protein Aggregates drug effects, Theobromine analysis, Cacao chemistry, Fermented Foods analysis
- Abstract
The metabolic profile of Lavado cocoa was characterized for the first time by NMR spectroscopy, then compared with the profiles of fermented and processed varieties, Natural and commercial cocoa. The significant difference in the contents of theobromine and flavanols prompted us to examine the cocoa varieties to seek correlations between these metabolite concentrations and the anti-amyloidogenic activity reported for cocoa in the literature. We combined NMR spectroscopy, preparative reversed-phase (RP) chromatography, atomic force microscopy, in vitro biochemical and cell assays, to investigate and compare the anti-amyloidogenic properties of extracts and fractions enriched in different metabolite classes. Lavado variety was the most active and the catechins and theobromine were the chemical components of cocoa hindering Aβ peptide on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
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44. Metabolomic profiling of beers: Combining 1 H NMR spectroscopy and chemometric approaches to discriminate craft and industrial products.
- Author
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Palmioli A, Alberici D, Ciaramelli C, and Airoldi C
- Subjects
- Multivariate Analysis, Beer analysis, Industry, Magnetic Resonance Spectroscopy, Metabolomics
- Abstract
The authentication and traceability of craft beers is an important issue for both beer consumers and producers. Reliable analytical methods able to identify and discriminate products are needed to protect the craft brew market against fraud and counterfeit. Here,
1 H NMR analysis of 31 beer samples, differing for beer style and brewing method (craft or industrial) was combined with multivariate statistical analysis, following both an untargeted and a targeted approach. NMR-based analysis of beer samples was sped developing a specific protocol enabling the automatic identification and quantification of metabolites in approximately thirty seconds per spectrum. A clear discrimination was achieved by exploiting1 H NMR analysis and multivariate chemometric methods and the targeted approach identified the metabolites responsible for the segregation. Overall, this study reports an analytical approach addressing beer traceability and is the starting point for the development of a standardized protocol for the discrimination of industrial and craft beers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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- View/download PDF
45. Coffee variety, origin and extraction procedure: Implications for coffee beneficial effects on human health.
- Author
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Ciaramelli C, Palmioli A, and Airoldi C
- Subjects
- Alkaloids analysis, Antioxidants chemistry, Chlorogenic Acid analysis, Coffea metabolism, Coffee chemistry, Humans, Magnetic Resonance Spectroscopy, Polymers analysis, Principal Component Analysis, Seeds chemistry, Seeds metabolism, Sonication, Caffeine analysis, Coffea chemistry
- Abstract
We set up an efficient protocol for the rapid analysis of NMR spectra of green and roasted coffee extracts, enabling the automatic identification and quantification of metabolites in approximately two minutes per spectrum. This method allowed for the metabolic profiling and the subsequent evaluation of the content of bioactive compounds and antioxidant activity of coffee samples, depending on their species (Arabica and Robusta), geographical origin and extraction procedure (hydroalcoholic, espresso and moka). The hydroalcoholic extraction is the most efficient method in terms of yields of low molecular weight compounds (in particular chlorogenic acids), while moka extraction provides the highest amounts of melanoidins. Moreover, that the ratio between health-giving compounds (chlorogenic acids, trigonelline and choline) and caffeine is higher in Arabica coffees. The data collected provide useful insights for the selection of coffee raw material to be used in the preparation of coffee-based dietary supplements, nutraceuticals and functional beverages., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
46. Glycan Carriers As Glycotools for Medicinal Chemistry Applications.
- Author
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Vacchini M, Edwards R, Guizzardi R, Palmioli A, Ciaramelli C, Paiotta A, Airoldi C, La Ferla B, and Cipolla L
- Subjects
- Animals, Biosensing Techniques methods, Dendrimers chemical synthesis, Dendrimers metabolism, Dendrimers therapeutic use, Drug Carriers chemical synthesis, Drug Carriers metabolism, Drug Carriers therapeutic use, Humans, Nanoparticles chemistry, Nanoparticles metabolism, Nanoparticles therapeutic use, Polysaccharides chemical synthesis, Polysaccharides metabolism, Protein Binding, Proteins metabolism, Chemistry, Pharmaceutical methods, Polysaccharides therapeutic use
- 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2019
- Full Text
- View/download PDF
47. NMR-driven identification of anti-amyloidogenic compounds in green and roasted coffee extracts.
- Author
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Ciaramelli C, Palmioli A, De Luigi A, Colombo L, Sala G, Riva C, Zoia CP, Salmona M, and Airoldi C
- Subjects
- Cell Line, Tumor, Color, Humans, Magnetic Resonance Spectroscopy, Amyloid beta-Peptides chemistry, Coffee chemistry, Food Handling, Plant Extracts chemistry, Plant Extracts pharmacology, Protein Multimerization drug effects
- Abstract
To identify food and beverages that provide the regular intake of natural compounds capable of interfering with toxic amyloidogenic aggregates, we developed an experimental protocol that combines NMR spectroscopy and atomic force microscopy, in vitro biochemical and cell assays to detect anti-Aβ molecules in natural edible matrices. We applied this approach to investigate the potential anti-amyloidogenic properties of coffee and its molecular constituents. Our data showed that green and roasted coffee extracts and their main components, 5-O-caffeoylquinic acid and melanoidins, can hinder Aβ on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line. Coffee extracts and melanoidins also counteract hydrogen peroxide- and rotenone-induced cytotoxicity and modulate some autophagic pathways in the same cell line., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
48. Structure-Activity Relationship in Monosaccharide-Based Toll-Like Receptor 4 (TLR4) Antagonists.
- Author
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Facchini FA, Zaffaroni L, Minotti A, Rapisarda S, Calabrese V, Forcella M, Fusi P, Airoldi C, Ciaramelli C, Billod JM, Schromm AB, Braun H, Palmer C, Beyaert R, Lapenta F, Jerala R, Pirianov G, Martin-Santamaria S, and Peri F
- Subjects
- Animals, Binding, Competitive drug effects, Cell Line, Fatty Acids chemistry, HEK293 Cells, Humans, Interleukin-8 biosynthesis, Ligands, Lipopolysaccharides metabolism, Mice, Models, Molecular, Molecular Conformation, Molecular Docking Simulation, Molecular Dynamics Simulation, Recombinant Proteins chemistry, Recombinant Proteins pharmacology, Signal Transduction drug effects, Structure-Activity Relationship, Monosaccharides chemistry, Monosaccharides pharmacology, Toll-Like Receptor 4 antagonists & inhibitors
- Abstract
The structure-activity relationship was investigated in a series of synthetic TLR4 antagonists formed by a glucosamine core linked to two phosphate esters and two linear carbon chains. Molecular modeling showed that the compounds with 10, 12, and 14 carbons chains are associated with higher stabilization of the MD-2/TLR4 antagonist conformation than in the case of the C16 variant. Binding experiments with human MD-2 showed that the C12 and C14 variants have higher affinity than C10, while the C16 variant did not interact with the protein. The molecules, with the exception of the C16 variant, inhibited the LPS-stimulated TLR4 signal in human and murine cells, and the antagonist potency mirrored the MD-2 affinity calculated from in vitro binding experiments. Fourier-transform infrared, nuclear magnetic resonance, and small angle X-ray scattering measurements suggested that the aggregation state in aqueous solution depends on fatty acid chain lengths and that this property can influence TLR4 activity in this series of compounds.
- Published
- 2018
- Full Text
- View/download PDF
49. Flavonoids in the Treatment of Alzheimer's and Other Neurodegenerative Diseases.
- Author
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Airoldi C, La Ferla B, D Orazio G, Ciaramelli C, and Palmioli A
- Subjects
- Humans, Flavonoids therapeutic use, Neurodegenerative Diseases drug therapy, Neuroprotective Agents therapeutic use
- 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
- Full Text
- View/download PDF
50. Natural Compounds in Cancer Prevention: Effects of Coffee Extracts and Their Main Polyphenolic Component, 5-O-Caffeoylquinic Acid, on Oncogenic Ras Proteins.
- Author
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Palmioli A, Ciaramelli C, Tisi R, Spinelli M, De Sanctis G, Sacco E, and Airoldi C
- Subjects
- Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic isolation & purification, Biological Products chemistry, Biological Products isolation & purification, Biological Products pharmacology, Breast Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Chlorogenic Acid analogs & derivatives, Chlorogenic Acid chemistry, Chlorogenic Acid isolation & purification, Chlorogenic Acid pharmacology, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Humans, Molecular Docking Simulation, Molecular Structure, Oncogene Protein p21(ras) metabolism, Plant Extracts chemistry, Plant Extracts isolation & purification, Polyphenols chemistry, Polyphenols isolation & purification, Polyphenols pharmacology, Quinic Acid analogs & derivatives, Quinic Acid chemistry, Quinic Acid isolation & purification, Quinic Acid pharmacology, Structure-Activity Relationship, Antineoplastic Agents, Phytogenic pharmacology, Breast Neoplasms drug therapy, Coffee chemistry, Oncogene Protein p21(ras) antagonists & inhibitors, Plant Extracts pharmacology
- Abstract
Recent epidemiological studies have demonstrated that the consumption of healthy foods that are particularly rich in polyphenols might reduce the incidence of cancer and neurodegenerative diseases. In particular, chlorogenic acids (CGAs) occur ubiquitously in food and represent the most abundant polyphenols in the human diet. A number of beneficial biological effects of CGAs, such as anti-inflammatory activity, anti-carcinogenic activity, and protection against neurodegenerative diseases, have been reported. However, the molecular mechanisms at the base of these biological activities have not yet been investigated in depth. By combining NMR spectroscopy, molecular docking, surface plasmon resonance and ex vivo assays of the Ras-dependent breast cancer cell line MDA-MB-231, we contribute to the elucidation of the molecular basis of the activity of CGAs and natural extracts from green and roasted coffee beans as chemoprotective dietary supplements., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
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