22 results on '"Norberto P, Lopes"'
Search Results
2. Improving annotation propagation on molecular networks through random walks: introducing ChemWalker
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Tiago C. Borelli, Gabriel Santos Arini, Luís G. P. Feitosa, Pieter C. Dorrestein, Norberto P. Lopes, and Ricardo R. da Silva
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Statistics and Probability ,Computational Mathematics ,Computational Theory and Mathematics ,Molecular Biology ,Biochemistry ,Computer Science Applications - Abstract
MotivationAnnotation of the mass signals is still the biggest bottleneck for the untargeted mass spectrometry analysis of complex mixtures. Molecular networks are being increasingly adopted by the mass spectrometry community as a tool to annotate large-scale experiments. We have previously shown that the process of propagating annotations from spectral library matches on molecular networks can be automated using Network Annotation Propagation (NAP). One of the limitations of NAP is that the information for the spectral matches is only propagated locally, to the first neighbor of a spectral match. Here, we show that annotation propagation can be expanded to nodes not directly connected to spectral matches using random walks on graphs, introducing the ChemWalker python library.ResultsSimilarly to NAP, ChemWalker relies on combinatorial in silico fragmentation results, performed by MetFrag, searching biologically relevant databases. Departing from the combination of a spectral network and the structural similarity among candidate structures, we have used MetFusion Scoring function to create a weight function, producing a weighted graph. This graph was subsequently used by the random walk to calculate the probability of ‘walking’ through a set of candidates, departing from seed nodes (represented by spectral library matches). This approach allowed the information propagation to nodes not directly connected to the spectral library match. Compared with NAP, ChemWalker has a series of improvements, on running time, scalability and maintainability and is available as a standalone python package.Availability and implementationChemWalker is freely available at https://github.com/computational-chemical-biology/ChemWalkerContactridasilva@usp.brSupplementary informationSupplementary data are available at Bioinformatics online.
- Published
- 2023
3. Repurposing of 5-nitrofuran-3,5-disubstituted isoxazoles: A thriving scaffold to antitrypanosomal agents
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Diego B. Carvalho, Amarith R. das Neves, Gisele B. Portapilla, Ozildeia Soares, Larissa B. B. Santos, Jefferson R. S. Oliveira, Luan S. Vianna, Wagner A. S. Judice, Iara A. Cardoso, Pedro H. Luccas, M. Cristina Nonato, Norberto P. Lopes, Sergio de Albuquerque, and Adriano C. M. Baroni
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Drug Discovery ,Pharmaceutical Science - Abstract
Chagas disease (CD) is a neglected disease caused by the protozoan Trypanosoma cruzi. The two drugs used in the treatment schedules exhibit adverse effects and severe toxicity. Thus, searching for new antitrypanosomal agents is urgent to provide improved treatments to those affected by this disease. 5-Nitrofuran-isoxazole analogs were synthesized by cycloaddition reactions [3+2] between chloro-oximes and acetylenes in satisfactory yields. We analyzed the structure-activity relationship of the analogs based on Hammett's and Hansch's parameters. The 5-nitrofuran-isoxazole analogs exhibited relevant in vitro antitrypanosomal activity against the amastigote forms of T. cruzi. Analog 7s was the trending hit of the series, showing an IC
- Published
- 2022
4. Design, synthesis and antitrypanosomatid activity of 2-nitroimidazole-3,5-disubstituded isoxazole compounds based on benznidazole
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Diego B. Carvalho, Pedro A.N. Costa, Gisele B. Portapilla, Amarith R. das Neves, Cristiane Y.K. Shiguemoto, Bruno I. Pelizaro, Fernanda Silva, Eliane M. Piranda, Carla C.P. Arruda, Priscyla D.M. Gaspari, Iara A. Cardoso, Pedro H. Luccas, M. Cristina Nonato, Norberto P. Lopes, Sergio de Albuquerque, and Adriano C.M. Baroni
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Pharmacology ,Organic Chemistry ,Drug Discovery ,General Medicine - Published
- 2023
5. Rosemary (Rosmarinus officinalis L.) Glycolic Extract Protects Liver Mitochondria from Oxidative Damage and Prevents Acetaminophen-Induced Hepatotoxicity
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Natalia S. S. Guimarães, Vyctória S. Ramos, Laura F. L. Prado-Souza, Rayssa M. Lopes, Gabriel S. Arini, Luís G. P. Feitosa, Ricardo R. Silva, Iseli L. Nantes, Debora C. Damasceno, Norberto P. Lopes, and Tiago Rodrigues
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mitochondria ,antioxidant ,Physiology ,Clinical Biochemistry ,oxidative stress ,hepatoprotection ,rosemary ,Cell Biology ,Molecular Biology ,Biochemistry ,acetaminophen - Abstract
Rosmarinus officinalis L. (rosemary) is an aromatic culinary herb. Native to the Mediterranean region, it is currently cultivated worldwide. In addition to its use as a condiment in food preparation and in teas, rosemary has been widely employed in folk medicine and cosmetics. Several beneficial effects have been described for rosemary, including antimicrobial and antioxidant activities. Here, we investigated the mechanisms accounting for the antioxidant activity of the glycolic extract of R. officinalis (Ro) in isolated rat liver mitochondria (RLM) under oxidative stress conditions. We also investigated its protective effect against acetaminophen-induced hepatotoxicity in vivo. A crude extract was obtained by fractionated percolation, using propylene glycol as a solvent due to its polarity and cosmeceutical compatibility. The quantification of substances with recognized antioxidant action revealed the presence of phenols and flavonoids. Dereplication studies carried out through LC-MS/MS and GC-MS, supported by The Global Natural Product Social Molecular Networking (GNPS) platform, annotated several phenolic compounds, confirming the previous observation. In accordance, Ro decreased the production of reactive oxygen species (ROS) elicited by Fe2+ or t-BOOH and inhibited the lipid peroxidation of mitochondrial membranes in a concentration-dependent manner in RLM. Such an effect was also observed in liposomes as membrane models. Ro also prevented the oxidation of mitochondrial protein thiol groups and reduced glutathione (GSH). In model systems, Ro exhibited a potent scavenger activity toward 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radicals and superoxide anions. It also demonstrated an Fe2+ chelating activity. Moreover, Ro did not exhibit cytotoxicity or dissipate the mitochondrial membrane potential (∆Ψ) in rat liver fibroblasts (BRL3A cells). To evaluate whether such antioxidant protective activity observed in vitro could also be achieved in vivo, a well-established model of hepatotoxicity induced by acute exposure to acetaminophen (AAP) was used. This model depletes GSH and promotes oxidative-stress-mediated tissue damage. The treatment of rats with 0.05% Ro, administered intraperitoneally for four days, resulted in inhibition of AAP-induced lipid peroxidation of the liver and the prevention of hepatotoxicity, maintaining alanine and aspartate aminotransferase (ALT/AST) levels equal to those of the normal, non-treated rats. Together, these findings highlight the potent antioxidant activity of rosemary, which is able to protect mitochondria from oxidative damage in vitro, and effects such as the antioxidant and hepatoprotective effects observed in vivo.
- Published
- 2023
6. Evaluation of ion mobility spectrometry for improving constitutional assignment in natural product mixtures
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Fausto Carnevale Neto, Trevor N. Clark, Norberto P. Lopes, and Roger G. Linington
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Pharmacology ,Biological Products ,Cross-Sectional Studies ,Complementary and alternative medicine ,Plant Extracts ,Tandem Mass Spectrometry ,Organic Chemistry ,Drug Discovery ,Ion Mobility Spectrometry ,Pharmaceutical Science ,Molecular Medicine ,EXTRATOS (FORMAS FARMACÊUTICAS) ,Analytical Chemistry - Abstract
The comprehensive chemical characterization of biological samples remains a central challenge in the field of natural products. Conventional workflows using liquid chromatography (LC)-coupled high-resolution tandem mass spectrometry (MS/MS or MS
- Published
- 2022
7. Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
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Alexandre G. Maganin, Guilherme R. Souza, Miriam D. Fonseca, Alexandre H. Lopes, Rafaela M. Guimarães, André Dagostin, Nerry T. Cecilio, Atlante S. Mendes, William A. Gonçalves, Conceição E.A. Silva, Francisco Isaac Fernandes Gomes, Lucas M. Mauriz Marques, Rangel L. Silva, Letícia M. Arruda, Denis A. Santana, Henrique Lemos, Lei Huang, Marcela Davoli-Ferreira, Danielle Santana-Coelho, Morena B. Sant’Anna, Ricardo Kusuda, Jhimmy Talbot, Gabriela Pacholczyk, Gabriela A. Buqui, Norberto P. Lopes, Jose C. Alves-Filho, Ricardo M. Leão, Jason C. O’Connor, Fernando Q. Cunha, Andrew Mellor, and Thiago M. Cunha
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Mice ,Animals ,Neuralgia ,Indoleamine-Pyrrole 2,3,-Dioxygenase ,General Medicine ,Dendritic Cells ,Quinolinic Acid ,Kynurenine ,Metabolic Networks and Pathways - Abstract
Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase-expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase-derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain.
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- 2021
8. Meningeal dendritic cells-astrocytes interactions elevate the kynurenine metabolic pathway to sustain neuropathic pain
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Guilherme R. Souza, Fernando Q. Cunha, Miriam D. Fonseca, Alexandre H. Lopes, Morena Brazil Sant'Anna, Rangel L. Silva, Gabriela A. Buqui, Jhimmy Talbot, Jason C. O’Connor, Thiago M. Cunha, Rafaela M. Guimarães, Dênis Augusto Reis Santana, Alexandre Gomes de Macedo Maganin, Norberto P. Lopes, Ricardo M. Leão, Atlante S. Mendes, Nerry T. Cecilio, Andre Dagostin, Gabriela Pacholczyk, Letícia Magalhães Arruda, Danielle S. Coelho, Marcela Davoli-Ferreira, Henrique Lemos, Lei Huang, Ricardo Kusuda, José C. Alves-Filho, Lucas Miranda Marques, Andrew L. Mellor, and Francisco Isaac Fernandes Gomes
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business.industry ,Chronic pain ,Pharmacology ,medicine.disease ,Spinal cord ,Somatosensory system ,Pathophysiology ,Metabolic pathway ,chemistry.chemical_compound ,medicine.anatomical_structure ,Downregulation and upregulation ,chemistry ,Neuropathic pain ,medicine ,business ,Kynurenine - Abstract
Neuropathic pain is triggered by injury to the somatosensory system, and is one of the most important types of chronic pain. Nevertheless, critical pathophysiological mechanisms that maintain neuropathic pain are poorly understood. Here, we show that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase (IDO) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO upregulation in dendritic cells that accumulate in the dorsal root leptomeninges led to increased levels of kynurenine (Kyn) in the spinal cord, where Kyn is metabolized by astrocytes-expressed kynurenine-3-monooxygenase into a pro-nociceptive metabolite 3-hydroxykynurenine. In conclusion, these data reveal a novel role for KYNPATH as an important factor maintaining neuropathic pain during neuroimmune-glia cells interactions. This novel paradigm offers potential new targets for drug development against this type of chronic pain.
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- 2021
9. Correction to: Involvement of isoorientin in the antidepressant bioactivity of a flavonoid-rich extract from Passiflora edulis f. flavicarpa leaves
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Jovelina S. F. Alves, José I. Marques, Daniel P. Demarque, Layse R. F. Costa, Juliano G. Amaral, Norberto P. Lopes, Arnóbio A. da Silva-Júnior, Luiz A. L. Soares, Elaine C. Gavioli, Leandro De S. Ferreira, and Silvana M. Zucolotto
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General Pharmacology, Toxicology and Pharmaceutics - Published
- 2020
10. DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A
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Rangel L, Silva, Gabriela T, Silveira, Carlos W, Wanderlei, Nerry T, Cecilio, Alexandre G M, Maganin, Marcelo, Franchin, Lucas M M, Marques, Norberto P, Lopes, José A, Crippa, Francisco S, Guimarães, José C F, Alves-Filho, Fernando Q, Cunha, and Thiago M, Cunha
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Secretory Pathway ,Adenosine A2 Receptor Agonists ,Dose-Response Relationship, Drug ,Receptor, Adenosine A2A ,Cell Survival ,THP-1 Cells ,Tumor Necrosis Factor-alpha ,Macrophages ,NF-kappa B ,p38 Mitogen-Activated Protein Kinases ,Inhibitory Concentration 50 ,Mice ,RAW 264.7 Cells ,Animals ,Cannabidiol ,Humans ,Phosphorylation ,Signal Transduction - Abstract
Cannabidiol (CBD) is a natural compound with psychoactive therapeutic properties well described. Conversely, the immunological effects of CBD are still poorly explored. In this study, the potential anti-inflammatory effects and underlying mechanisms of CBD and its analog Dimethyl-Heptyl-Cannabidiol (DMH-CBD) were investigated using RAW 264.7 macrophages. CBD and DMH-CBD suppressed LPS-induced TNF production and NF-kB activity in a concentration-dependent manner. Both compounds reduced the NF-kB activity in a μM concentration range: CBD (IC
- Published
- 2018
11. Metabolomic Fingerprinting of Salinispora From Atlantic Oceanic Islands
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Anelize Bauermeister, Karen Velasco-Alzate, Tiago Dias, Helena Macedo, Elthon G. Ferreira, Paula C. Jimenez, Tito M. C. Lotufo, Norberto P. Lopes, Susana P. Gaudêncio, and Letícia V. Costa-Lotufo
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0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,lcsh:QR1-502 ,Biology ,Genome ,Microbiology ,lcsh:Microbiology ,03 medical and health sciences ,Metabolomics ,Genus ,14. Life underwater ,Secondary metabolism ,Original Research ,Salinispora ,geography ,molecular networking ,geography.geographical_feature_category ,Obligate ,BACTERIOLOGIA APLICADA ,16S ribosomal RNA ,biology.organism_classification ,LC-MS ,030104 developmental biology ,Micromonosporaceae ,Evolutionary biology ,Archipelago ,saliniketal ,metabolomic - Abstract
Salinispora (Micromonosporaceae) is an obligate marine bacterium genus consisting of three species that share over 99% 16S rRNA identity. The genome and biosynthetic pathways of the members of this genus have been widely investigated due to their production of species-specific metabolites. However, despite the species' high genetic similarity, site-specific secondary metabolic gene clusters have been found in Salinispora strains collected at different locations. Therefore, exploring the metabolic expression of Salinispora recovered from different sites may furnish insights into their environmental adaptation or their chemical communication and, further, may lead to the discovery of new natural products. We describe the first occurrence of Salinispora strains in sediments from the Saint Peter and Saint Paul Archipelago (a collection of islets in Brazil) in the Atlantic Ocean, and we investigate the metabolic profiles of these strains by employing mass-spectrometry-based metabolomic approaches, including molecular networking from the Global Natural Products Social Molecular Networking platform. Furthermore, we analyze data from Salinispora strains recovered from sediments from the Madeira Archipelago (Portugal, Macaronesia) in order to provide a wider metabolomic investigation of Salinispora strains from the Atlantic Oceanic islands. Overall, our study evidences a broader geographic influence on the secondary metabolism of Salinispora than was previously proposed. Still, some biosynthetic gene clusters, such as those corresponding to typical chemical signatures of S. arenicola, like saliniketals and rifamycins, are highly conserved among the assessed strains.
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- 2018
12. New cascarosides from Rhamnus purshiana and fragmentation studies of the class by ion trap mass spectrometry
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Daniel P, Demarque, Danielle R, Pinho, Daniel R, Callejon, Gibson G, de Oliveira, Denise B, Silva, Carlos A, Carollo, and Norberto P, Lopes
- Abstract
Anthrone and oxanthrone are important anthraquinone derivatives present in medicinal plants which are used in therapeutics as laxatives. Some of these plants need to be stored at least one year before they can be used in order to oxidize anthrones into oxanthrones, so to avoid severe diarrhea and dehydration. Therefore, this work aimed to characterize fragmentation reactions between these anthraquinones to provide an easy way to differentiate between the two classes, since it is necessary and important to discriminate and identify these derivatives in laxative plants and phytotherapic drugs.Anthrone (cascarosides A-D) and oxanthrone (10-hydroxycascaroside A and B) derivatives were isolated and identified by NMR (The additional hydroxyl at C-10 in oxanthrones allowed McLafferty-type rearrangements to form the quinone group in positive mode, while in negative mode the second sugar loss infringed the odd-electron rule and formed a radical fragment. No differences in fragmentation reactions were found between diastereoisomeric pairs, although the additional oxygen at C-10 of oxanthrones allowed a different fragmentation pattern.The proposed fragmentation patterns can be used to differentiate anthrones from oxanthrones in both ion modes. In addition, they can be applied to differentiate these compounds in anthraquinone-rich plants and phytotherapic drugs. Finally, herein, the strategy applied allowed us to identify new natural products. Copyright © 2017 John WileySons, Ltd.
- Published
- 2017
13. Hypericum perforatum Reduces Paracetamol-Induced Hepatotoxicity and Lethality in Mice by Modulating Inflammation and Oxidative Stress
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Miriam S N, Hohmann, Renato D R, Cardoso, Victor, Fattori, Nilton S, Arakawa, José C, Tomaz, Norberto P, Lopes, Rubia, Casagrande, and Waldiceu A, Verri
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Anthracenes ,Inflammation ,Male ,Plants, Medicinal ,Plant Extracts ,Terpenes ,Tumor Necrosis Factor-alpha ,Rutin ,Anti-Inflammatory Agents ,Alanine Transaminase ,Phloroglucinol ,Glutathione ,Antioxidants ,Mice ,Oxidative Stress ,Animals ,Quercetin ,Aspartate Aminotransferases ,Chemical and Drug Induced Liver Injury ,Perylene ,Hypericum ,Acetaminophen - Abstract
Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)-induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced lethality. Paracetamol-induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL-1β, TNF-α, and IFN-γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS˙(+) ) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol-induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol-induced cytokine production, neutrophil recruitment, and oxidative stress.
- Published
- 2015
14. Validation of analytical procedures using HPLC-ELSD to determine six sesquiterpene lactones in Eremanthus species
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João Paulo B, Sousa, Elídia F, Nogueira, Leandro S, Ferreira, Norberto P, Lopes, and João Luis C, Lopes
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Lactones ,Limit of Detection ,Plant Extracts ,Linear Models ,Reproducibility of Results ,Asteraceae ,Sesquiterpenes ,Chromatography, High Pressure Liquid - Abstract
Eremanthus species display sesquiterpene lactones with therapeutic potential. We are proposing the development of a new analytical method that has been completely validated to qualify Eremanthus species and its main lactones in raw material using HPLC-ELSD. For the sample preparation, 10.0 mg of powdered Eremanthus leaves was extracted with a 5 mL MeOH/H2 O (9:1 v/v) solution containing scopoletin at 140 µg/mL as the internal standard. For the separation of eight compounds, six of which were lactones, one internal (IS) and one secondary standard were performed utilizing monolithic columns with a nonlinear gradient. The selectivity, stability, precision and matrix effects parameters showed values of RSD of10%. The six lactones and scopoletin (IS) were recovered with a proportion between 74 and 90% with accuracy represented by error at -25.41%. The linear dynamic range was obtained between 10.0 and 310.0 µg/mL for all compounds with r(2) 0.9987. The limits of detection and quantitation ranged from 2.00 to 6.79 µg/mL and from 6.00 to 20.40 µg/mL, respectively. Assessing the robustness study, this method can be used in inter-laboratory studies. Using the HPLC-ELSD method, six sesquiterpene lactones including 4β,5-dihydro-2',3'-dihydroxy-15-deoxy-goyazensolide, goyazensolide, 4β,5-dihydro-2',3'-epoxy-15-deoxy-goyazensolide, centratherin, 4β,5-dihydro-15-deoxy-goyazensolide and lychnofolide, were detected and quantified from distinct Eremanthus species, which were collected in different regions.
- Published
- 2014
15. MALDI-MS of flavonoids: a systematic investigation of ionization and in-source dissociation mechanisms
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Denise B, Silva and Norberto P, Lopes
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Flavonoids ,Flavonols ,Molecular Structure ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Flavanones ,Hydroxybenzoates ,Glycosides ,Flavones - Abstract
Matrix assisted laser desorption ionization (MALDI) is a technique widely employed in the analysis of proteins and peptides, and nowadays it has also been applied to small molecules. There is little significant information regarding the in-source dissociation processes on MALDI for natural products. Twenty-six flavonoids (flavanones, flavones and flavonols) were analyzed by MALDI using different methods (with different matrices) and without matrix to comprehend the in-source reactions and establish good analysis methods for these compounds. Depending on the class, structure and the laser intensity applied, methoxylated flavonoid aglycones can eliminate methyl radicals (˙CH3) in the source, such as flavonols, but lithium 2,4-dihydroxybenzoate matrix suppresses the ˙CH3 eliminations and retro-Diels-Alder cleavages in the source. All of the flavonoid O-glycosides evaluated herein eliminated the sugar in source, even in the presence of the matrix, and its product radical ions ([M-H-sugar](-)˙) were observed in the negative mode. The flavone C-glycosides suffered intense dissociation, which was reduced by the addition of a matrix and the application of low laser intensity, mainly in the negative mode. Depending on the hydroxyl substituents, the [M-H-H](-)˙ ion was observed with variable relative intensity in the spectra.
- Published
- 2014
16. Preparation and in vitro evaluation of α and β-amyrins loaded nanoemulsions
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Ivanildes V, Rodrigues, Janaina B, Seibert, Simone P, Carneiro, Gustavo H B, de Souza, Orlando D H, dos Santos, and Norberto P, Lopes
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Drug Liberation ,Solubility ,Drug Compounding ,Nanoparticles ,Emulsions ,Oleanolic Acid ,Particle Size - Abstract
The triterpenes α- and β-amyrins display important pharmacological activities. As a result of their high hydrophobia, they present low water solubility and reflect poor oral bioavailability. Different techniques can be used for the improvement of amyrins solubility, one of them is the use of nanoemulsions. Therefore, the method of direct emulsification was used to develop a nanoemulsion of these triterpenes and the resulting drug delivery system was characterized by an in vitro release assay. Encapsulation efficiency higher than 99% was achieved with total release around 30% in 24 h, which suggests that this system could be useful for the administration of α- and β-amyrins by different routes in an efficient way.
- Published
- 2013
17. Electronic structure and gas-phase chemistry of protonated α- and β-quinonoid compounds: a mass spectrometry and computational study
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Ricardo, Vessecchi, Flávio S, Emery, Norberto P, Lopes, and Sérgio E, Galembeck
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Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Tandem Mass Spectrometry ,Gases ,Naphthoquinones - Abstract
The use of quinonoid compounds against tropical diseases and as antitumor agents has prompted the search for new naturally occurring and synthetic derivatives. Among these quinonoid compounds, lapachol and its isomers (α- and β-lapachone) serve as models for the synthesis of new compounds with biological activity, and the use of electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis as a tool to elucidate and characterize these products has furnished important information about these compounds.ESI-MS/MS analysis under collision-induced dissociation conditions was used to describe the fragmentation mechanisms for protonated 1,4-naphthoquinone, 1,2-naphthoquinone, α-lapachone, and β-lapachone. The B3LYP/6-31+G(d,p) model was used to obtain proton affinities, gas-phase basicities, and molecular electrostatic potential maps, thus indicating the probable protonation sites. Fragmentation pathways were suggested on the basis of the relative enthalpies of the product ions.The ESI-MS signals of the cationized molecules of ortho quinonoid compounds were more intense than those of the protonated molecule. Formation of the major product ions with m/z 187 from protonated α- and β-lapachone has been attributed to a retro-Diels-Alder (RDA) reaction.MS/MS studies on lapachol isomers (α- and β-lapachone) will facilitate the interpretation of the liquid chromatography (LC)-MS/MS analysis of new metabolites. MS/MS data on the 1,4-naphthoquinone, 1,2-naphthoquinone, α-lapachone and β-lapachone core will help characterize new derivatives from in vitro/in vivo metabolism studies in complex matrices. The product ions revealed the major fragmentation mechanisms and these ions will serve as diagnostic ions to identify each studied compound.
- Published
- 2012
18. Gas-phase reactivity of 2-hydroxy-1,4-naphthoquinones: a computational and mass spectrometry study of lapachol congeners
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Ricardo, Vessecchi, Flávio S, Emery, Sérgio E, Galembeck, and Norberto P, Lopes
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Ions ,Models, Molecular ,Spectrometry, Mass, Electrospray Ionization ,Tandem Mass Spectrometry ,Thermodynamics ,Computer Simulation ,Protons ,Naphthoquinones - Abstract
In order to understand the influence of alkyl side chains on the gas-phase reactivity of 1,4-naphthoquinone derivatives, some 2-hydroxy-1,4-naphthoquinone derivatives have been prepared and studied by electrospray ionization tandem mass spectrometry in combination with computational quantum chemistry calculations. Protonation and deprotonation sites were suggested on the basis of gas-phase basicity, proton affinity, gas-phase acidity (ΔG(acid) ), atomic charges and frontier orbital analyses. The nature of the intramolecular interaction as well as of the hydrogen bond in the systems was investigated by the atoms-in-molecules theory and the natural bond orbital analysis. The results were compared with data published for lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone). For the protonated molecules, water elimination was verified to occur at lower proportion when compared with side chain elimination, as evidenced in earlier studies on lapachol. The side chain at position C(3) was found to play important roles in the fragmentation mechanisms of these compounds.
- Published
- 2012
19. Re-examination of the anion derivatives of isoflavones by radical fragmentation in negative electrospray ionization tandem mass spectrometry: experimental and computational studies
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Ricardo, Vessecchi, Guilherme Julião, Zocolo, Dayana Rubio, Gouvea, Florian, Hübner, Benedikt, Cramer, Mary Rosa Rodrigues, de Marchi, Hans-Ulrich, Humpf, and Norberto P, Lopes
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Anions ,Spectrometry, Mass, Electrospray Ionization ,Tandem Mass Spectrometry ,Computer Simulation ,Gases ,Isoflavones - Abstract
This paper reports theoretical and experimental studies of gas-phase fragmentation reactions of four naturally occurring isoflavones. The samples were analyzed in negative ion mode by direct infusion in ESI-QqQ, ESI-QqTOF and ESI-Orbitrap systems. The MS/MS and MS(n) spectra are in agreement with the fragmentation proposals and high-resolution analyses have confirmed the formulae for each ion observed. As expected, compounds with methoxyl aromatic substitution have showed a radical elimination of •CH(3) as the main fragmentation pathway. A second radical loss (•H) occurs as previously observed for compounds which exhibit a previous homolytic •CH(3) cleavage (radical anion) and involves radical resonance to stabilize the anion formed. However, in this study we suggest another mechanism for the formation of the main ions, on the basis of the enthalpies for each species. Compounds without methoxy substituent dissociate at the highest energies and exhibit the deprotonated molecule as the most intense ion. Finally, energy-resolved experiments were carried out to give more details about the gas-phase dissociation reaction of the isoflavones and the results are in agreement with the theoretical approaches.
- Published
- 2011
20. Fragmentation studies and electrospray ionization mass spectrometry of lapachol: protonated, deprotonated and cationized species
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Ricardo, Vessecchi, Flavio S, Emery, Sérgio E, Galembeck, and Norberto P, Lopes
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Spectrometry, Mass, Electrospray Ionization ,Models, Chemical ,Phase Transition ,Naphthoquinones - Abstract
Electrospray ionization mass spectrometric analysis of lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone) was accomplished in order to elucidate the gas-phase dissociation reactions of this important biologically active natural product. The occurrence of protonated and cationized species in the positive mode and of deprotonated species in the negative mode was explored by means of collision-induced dissociation (CID) experiments. For the protonated molecule, the H(2)O and C(4)H(8) losses occur by two competitive channels. For the deprotonated molecule, the even-electron rule is not conserved, and the radicalar species are eliminated by formation of distonic anions. The fragmentation mechanism for each ion was suggested on the basis of computational thermochemistry. Atomic charges, relative energies, and frontier orbitals were employed aiming at a better understanding of the gas-phase reactivity of lapachol. Potential energy surfaces for fragmentation reactions were obtained by the B3LYP/6-31+G(d,p) model.
- Published
- 2010
21. Gas-phase dissociation of 1,4-naphthoquinone derivative anions by electrospray ionization tandem mass spectrometry
- Author
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Ricardo, Vessecchi, Carlos A, Carollo, José N C, Lopes, Antonio E M, Crotti, Norberto P, Lopes, and Sérgio E, Galembeck
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Molecular Structure ,Tandem Mass Spectrometry ,Thermodynamics ,Antineoplastic Agents ,Pesticides ,Phase Transition ,Naphthoquinones - Abstract
Gas-phase dissociation pathways of deprotonated 1,4-naphthoquinone (NQ) derivatives have been investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The major decomposition routes have been elucidated on the basis of quantum chemical calculations at the B3LYP/6-31 + G(d,p) level. Deprotonation sites have been indicated by analysis of natural charges and gas-phase acidity. NQ anions underwent an interesting reaction under collision-induced dissociation conditions, which resulted in the radical elimination of the lateral chain, in contrast with the even-electron rule. Possible pathways have been suggested, and their mechanisms have been elucidated on the basis of Gibbs energy and enthalpy values for the anions previously described at each pathway.
- Published
- 2009
22. Negative ion 'chip-based' nanospray tandem mass spectrometry for the analysis of flavonoids in glandular trichomes of Lychnophora ericoides Mart. (Asteraceae)
- Author
-
Leonardo, Gobbo-Neto, Paul J, Gates, and Norberto P, Lopes
- Subjects
Flavonoids ,Plant Leaves ,Tandem Mass Spectrometry ,Microchip Analytical Procedures ,Spectrometry, Mass, Secondary Ion ,Asteraceae - Abstract
This paper reports a method for the analysis of secondary metabolites stored in glandular trichomes, employing negative ion 'chip-based' nanospray tandem mass spectrometry. The analyses of glandular trichomes from Lychnophora ericoides, a plant endemic to the Brazilian 'cerrado' and used in traditional medicine as an anti-inflammatory and analgesic agent, led to the identification of five flavonoids (chrysin, pinocembrin, pinostrobin, pinobanksin and 3-O-acetylpinobanksin) by direct infusion of the extracts of glandular trichomes into the nanospray ionisation source. All the flavonoids have no oxidation at ring B, which resulted in a modification of the fragmentation pathways compared with that of the oxidised 3,4-dihydroflavonoids already described in the literature. The absence of the anti-inflammatory and antioxidant di-C-glucosylflavone vicenin-2, or any other flavonoid glycosides, in the glandular trichomes was also demonstrated. The use of the 'chip-based' nanospray QqTOF apparatus is a new fast and useful tool for the identification of secondary metabolites stored in the glandular trichomes, which can be useful for chemotaxonomic studies based on metabolites from glandular trichomes.
- Published
- 2008
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