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White teeth can give confidence and tend to be associated with a healthier lifestyle in modern society. Therefore, modern tooth bleaching strategies have been developed, including the use of hydrogen peroxide and peroxymonosulfate. Although both molecules are oxidizing agents, their effects on the molecular composition of the stained teeth are yet to be determined. In this study, the molecular profiles of teeth bleached with these two different bleaching procedures were compared using liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). GNPS spectral libraries and SIRIUS were used to perform metabolite annotation. The analysis revealed amino acids, dipeptides, and derivatives in peroxymonosulfate and H2O2 treated samples were altered compared to non-bleached sample controls. Additionally, the two bleaching methods led to distinct molecular profiles. For example, diterpenoids were more prevalent after peroxymonosulfate treatment, while treatment with H2O2 resulted in a greater abundance of alkaloids. This work elucidates the biochemical changes resulting from different tooth-whitening strategies.

Made available in DSpace on 2022-04-29T08:36:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Eight phenolic compounds were isolated from Eugenia pyriformis leaves fraction by semi-preparative HPLC and characterized by Nuclear Magnetic Resonance (NMR) and mass spectrometry (ESI-MS). Five compounds were isolated and identified for the first time in E. pyriformis species, while this is the first report of the accumulation of isoquercitrin, quercitrin, and the aglycone quercetin in its leaves. E. pyriformis leaves and fruits extracts, as well as the compounds isolated from the leaves most active fraction, were evaluated for their antiglycation and antioxidant activities. The mixture of myricetin-3-O-(2″-O-galloyl)-α-L-rhamnoside and myricetin-3-O-(4″-O-galloyl)-α-L-rhamnoside showed the highest antiglycation activity. These results suggest that this species is a promising source of bioactive compounds. Further studies to investigate the inhibition of the glycation process in vivo are necessary to evaluate its use in the treatment and/or prevention of advanced glycation end-products (AGEs)-associated diseases. Laboratory of Phytochemistry and Biomolecules (LabFitoBio) Department of Chemistry State University of Londrina (UEL) Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP) BioSmart Nanotechnology LTDA Me Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of public MS/MS spectra. Annotations were propagated based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer’s brain phenotype. The nearest neighbor suspect spectral library is openly available through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

Made available in DSpace on 2020-12-12T01:33:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 The thermal behavior of two commercially available sweeteners based on Stevia rebaudiana Bertoni was studied by TG–DSC and EGA. The composition prior and after heating was analyzed by LC–MS/MS to identify the steviol glycosides present in each formulation and thermal degradation products, respectively. The two formulations (S1 and S2) presented thermal stability up to at least 200 °C. By DSC, it was possible to identify the presence of rebaudioside (REB) C and REB A in S1. S2 was composed mainly by erythritol (confirmed by both DSC and FTIR), REB A and E. By LC–MS/MS analyses, it was possible to observe that S1 is composed mainly by stevioside and REB A, E, C and B, and that the major products formed after heating are, basically, partially deglycosylated steviol structures. The thermal decomposition products were different depending on the formulation employed. These chemical changes in the compounds’ properties can cause a change in the desired taste and solubility of the formulations. Instituto Federal de Educação Ciência e Tecnologia de Rondônia (IFRO), Campus Ji-Paraná Instituto de Química Universidade Estadual Paulista (Unesp) Faculdade de Ciências Universidade Estadual Paulista (Unesp) Instituto de Química Universidade Estadual Paulista (Unesp) Faculdade de Ciências Universidade Estadual Paulista (Unesp)

Made available in DSpace on 2020-12-12T02:13:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 In this study, the chemical composition, total phenolic content and antioxidant activity (DPPH, ORAC and FRAP assays) of A. subrufescens and P. ostreatus, cultivated with handmade and commercials supplements, were compared. Additionally, the compounds ergosterol, saccharopine, and hexitol were identified in A. subrufescens by HPLC-MS/MS. The antioxidant compound p-coumaric acid and dihexoses was found in both mushroom species. A. subrufescens presented higher total phenolic content (73.8 ± 0.6 mg GAE 100 g−1) and antioxidant activity than P. ostreatus (16.6 ± 0.5 mg GAE 100 g−1). The handmade supplement based on the waste of noble grains presented statistically similar phenolic content to the mushrooms cultivated with commercial ones Spawn Mate II SE (86.1 ± 1.4 and 92.9 ± 0.3 mg GAE 100 g−1, respectively). Therefore, the results support the use of handmade supplements based on agro-wastes as a viable alternative to the use of high-cost commercial ones. Laboratory of Phytochemistry and Biomolecules (LabFitoBio) Department of Chemistry State University of Londrina (UEL), Rodovia Celso Garcia Cid | Pr 445 Km 380 NuBBE Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), Av. Prof. Francisco Degni, 55 Faculty of Agrarian and Technological Sciences São Paulo State University (UNESP), Rod. Cmte João Ribeiro de Barros, km 651 Departament of Chemistry Faculty of Sciences São Paulo State University (UNESP), Av Eng° Luiz Edmundo Carrijo Coube, S/N NuBBE Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), Av. Prof. Francisco Degni, 55 Faculty of Agrarian and Technological Sciences São Paulo State University (UNESP), Rod. Cmte João Ribeiro de Barros, km 651 Departament of Chemistry Faculty of Sciences São Paulo State University (UNESP), Av Eng° Luiz Edmundo Carrijo Coube, S/N

Made available in DSpace on 2020-12-12T02:08:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Introduction: Crotalaria spectabilis is an important species used as a pre-plant cover for soybean crops to control the proliferation of endoparasitic nematodes. Species from the Crotalaria genus are known for presenting pyrrolizidine alkaloids (PAs) in their composition, however, C. spectabilis is still considered chemically under-explored. Objective: The goal of this manuscript is the development and validation of a method for PAs and flavonoids identification and quantification of C. spectabilis seeds and leaves, a toxic plant used for nematode proliferation control in soil, especially in soybean crops. Materials and methods: Seeds and leaves extracts were analysed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the identification of the compounds. Results: PAs and phenolic compounds could be identified in both samples based on the MS/MS fragmentation pattern. Molecular formulas of the annotated compounds were confirmed by ultra-high-performace liquid chromatography-quadrupole time-of-flight (UHPLC-QToF), and monocrotaline could also be confirmed by standard comparison. The quantification of monocrotaline was performed by HPLC-MS/MS, resulting in 123 times higher monocrotaline content in seeds than in the leaves, which could explain its efficiency in combating nematode proliferation in soil. Conclusion: This was the first report of phenolic compounds in C. spectabilis. The current study highlights the importance of C. spectabilis for nematode control due to the presence of toxic PAs, and the employment of analytical techniques for identification and quantification of compounds present in the extracts. Laboratory of Phytochemistry and Biomolecules (LabFitoBio) Department of Chemistry State University of Londrina (UEL) Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP) Brazilian Agricultural Research Corporation – Embrapa Soybean Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)

In Brazil, research with natural products had a strong impulse when FAPESP supported the creation of the Laboratory of Chemistry of Natural Products of the Institute of Chemistry of USP (1966). In 1999, FAPESP launched the Research Program in the Characterization, Conservation, Restoration and Sustainable Use of Biodiversity (BIOTA-FAPESP), which intensified the sustainable exploitation of biodiversity, and which evolved to form the Biota Network for Bioprospection and Bioassays (BIOprospecTA), which integrates groups from all over the country, optimizing the use of the skills already installed for the bioprospecting of microorganisms, plants, invertebrates, vertebrates and marine organisms. Of the 104 projects related to plant sciences, 35 carried out bioprospection of Brazilian flora, belonging to the areas of Chemistry, Botany, Genetics, Plant Physiology, Plant Morphology, Plant (Chemo)taxonomy, Ecosystem Ecology, Plant Genetics. Physical Sciences, Forest Resources, Forestry Engineering, Agronomy, leading to thousands of publications, engagement of hundreds of students and a deeper understanding of natural products in different biological models through macromolecules analysis aided by computational and spectrometric strategies, in addition to pharmacological evaluations. The development of omics approaches led to a more comprehensive view of the chemical profile of an organism, and enabled integrated and concomitant studies of several samples, and faster annotation of known molecules, through the use of hyphenated and chemometric techniques, and molecular networking. This also helped to overcome the lack of information on the safety and efficacy of herbal preparations, in projects dealing with the standardization of herbal products, according to international standards. The BIOTA-FAPESP program has also focused on environmental aspects, in accordance with the principles of Green Chemistry and has had positive effects on international collaboration, on the number and impact of scientific publications and on partnership with companies, a crucial step to add value and expand the production chain of bioproducts. Also, the compilation, systematization and sharing of data were contemplated with the creation of the NUBBEDB database, of free access, and that integrates with international databases (ACD/labs, American Chemical Society – ACS), helping researchers and companies in the development from different areas of science, technology, strengthening the bioeconomy and subsidizing public policies. Resumo No Brasil, as pesquisas com produtos naturais tiveram um forte impulso quando a FAPESP apoiou a criação do Laboratório de Química de Produtos Naturais do Instituto de Química da USP (1966). Em 1999, a FAPESP lançou o Programa de Pesquisa em Caracterização, Conservação, Restauração e Uso Sustentável da Biodiversidade (BIOTA-FAPESP), que intensificou a exploração sustentável da biodiversidade, e que evoluiu para formar a Rede Biota de Bioprospecção e Bioensaios (BIOprospecTA), que integra grupos de todo o país, otimizando o aproveitamento das competências já instaladas para a bioprospecção de microrganismos, plantas, invertebrados, vertebrados e organismos marinhos. Dos 104 projetos relacionados às ciências vegetais, 35 realizaram a bioprospecção da flora brasileira, em diversas áreas como Química, Botânica, Fisiologia e Morfologia Vegetal, (Quimio)taxonomia Vegetal, Ecologia de Ecossistemas, Genética Vegetal, Recursos Florestais, Engenharia Florestal, dentre outros, levando a milhares de publicações, ao engajamento de centenas de estudantes e ao entendimento mais profundo dos produtos naturais em diferentes modelos biológicos por meio da análise de micromoléculas auxiliada por estratégias computacionais e espectrométricas, além de avaliações farmacológicas. O desenvolvimento de abordagens ômicas ampliou a visão sobre perfil químico dos organismos, possibilitou o estudo integrado e concomitante de várias amostras, e a anotação mais rápida de moléculas conhecidas, por meio do uso de técnicas hifenadas, quimiométricas e redes moleculares. Isso também contribuiu para superar a falta de informação sobre a segurança e eficácia dos fitopreparados, em projetos que tratam da padronização de produtos fitoterápicos, de acordo com normas internacionais. O programa BIOTA-FAPESP também tem focado em aspectos ambientais, de acordo com os princípios da Química Verde e teve reflexos positivos na colaboração internacional, no número e no impacto das publicações científicas e na parceria com empresas, etapa crucial para agregar valor e expandir a cadeia produtiva de bioprodutos. Ainda, a compilação, sistematização e compartilhamento de dados foram contemplados com a criação da base de dados NUBBEDB, de livre acesso, e que se integra com bases internacionais (ACD/labs, American Chemical Society – ACS), auxiliando pesquisadores e empresas no desenvolvimento de diferentes áreas da ciência, tecnologia, fortalecendo a bioeconomia e subsidiando políticas públicas.

Made available in DSpace on 2022-04-29T08:30:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-30 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundacion Araucaria Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Exploratory factor analysis was applied to determine the chemical differences between fruitbodies of three Agaricus subrufescens mushroom strains [from Japan (JP), Brazil (ABZ), and Belgium (T2)] grown with handmade and commercial supplements. The composition of the ABZ strain cultivated with agro-industrial waste supplement presented a high nutritional composition regarding the amounts of fibre and protein, similar to mushrooms cultivated with the commercial supplement. The chromatographic fingerprints obtained for T2 and JP strains grown with commercial supplements presented similar profiles compared to those cultivated with the supplement based on peanut and the mix of supplements. The chromatographic analysis also showed that the similarities are correlated with the relative abundance of antioxidant compounds annotated by HPLC-MS, such as vanillic acid deoxyhexoside, caffeic acid hexoside, catechin hexosemalonate, digallic acid, cinnamic acid derivative, and p-coumaroylmalic acid. This study showed that handmade supplements based on agro-industrial waste could be viable alternatives for replacing high-cost supplements. Laboratory of Phytochemistry and Biomolecules (LabFitoBio) Department of Chemistry State University of Londrina (UEL) Laboratory of Chemometrics in Natural Sciences (LQCN) Department of Chemistry State University of Londrina, 6001 Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP) Faculty of Agrarian and Technological Sciences São Paulo State University (UNESP) Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP) Faculty of Agrarian and Technological Sciences São Paulo State University (UNESP)

Made available in DSpace on 2021-06-25T10:55:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01. Added 1 bitstream(s) on 2021-07-15T15:05:25Z : No. of bitstreams: 1 S0103-50532021000400786.pdf: 944248 bytes, checksum: 167925933dc0ec4ec63ea2afbf080153 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Platonia insignis fruit, popularly known as bacuri, is traditionally used in folk medicine for its anti-inflammatory and antioxidant properties. Therefore, this study determined the chemical composition and biological activities of the bacuri’s shell and seeds extracts, considered residues from its consumption and industrial uses. Four biflavonoids (GB-2a, GB-1a, morelloflavone, and volkensiflavone) were identified in the extracts by high-performance liquid chromatography-diode array detection (HPLC-DAD), liquid chromatography tandem mass spectrometry (LC-MS/MS), and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) techniques. Morelloflavone was identified as the main compound in the shell ethyl acetate extract, being responsible for the high in vitro antioxidant (50% effective concentration (EC50) ranging from 8.0-10.5 µg mL−1 in different protocols), anti-glycant (80%), and moderate inhibition of nitric oxide (1.56 µg mL−1 for > 90% cell viability) activities. This extract showed promising in vivo anti-inflammatory activity evaluated through the paw edema protocol after its incorporation into a liquid-crystalline drug carrier system, reducing the edema by up to 31%. The results demonstrated the potential of the fruit for the development of drugs of natural origin and corroborated to add economic value to these discarded residues. Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Departamento de Fármacos e Medicamentos Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Laboratório de Fitoquímica e Biomoléculas (LabFitoBio) Departamento de Química Universidade Estadual de Londrina (UEL) Faculdade de Ciências Exatas e Tecnologia (FACET) Universidade Federal da Grande Dourados (UFGD) Departamento de Genética e Morfologia Universidade de Brasília (UnB) Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Núcleo de Bioensaios Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Departamento de Fármacos e Medicamentos Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Júlio de Mesquita Filho” (Unesp) CNPq: 142014/2018-4 CNPq: 159735/2017-3 FAPESP: 2013/07600-3 CNPq: 2014/465637-0 FAPESP: 2014/50926-0 FAPESP: 2016/16970-7 FAPESP: 2017/18807-9 FAPESP: 2017/19870-6

Microbiota are a malleable part of ecosystems, including the human ecosystem. Microorganisms not only affect the chemistry of their specific niche, such as the human gut but also the chemistry of distant environments, such as other parts of the body. Mass spectrometry-based metabolomics is one of the key technologies to detect and identify the small molecules produced by the human microbiome, and to understand the functional role of these microbial metabolites. This Review aims to provide a foundational introduction to common forms of untargeted mass spectrometry and the types of data that can be obtained in the context of microbiome analysis. Data analysis remains an obstacle, therefore, the emphasis is placed on data analysis approaches and integrative analysis, including the integration of microbiome sequencing data.

Molecular networking connects tandem mass spectra of molecules based on the similarity of their fragmentation patterns. However, during ionization, molecules commonly form multiple ion species with different fragmentation behavior. To connect ion species of the same molecule, we developed Ion Identity Molecular Networking. These new relationships improve network connectivity, are shown to reveal novel ion-ligand complexes, enhance annotation within molecular networks, and facilitate the expansion of spectral libraries. Fil: Schmid, Robin. University Of Munster; Alemania Fil: Petras, Daniel. University Of California At San Diego. Skaggs School Of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center.; Estados Unidos Fil: Nothias, Louis Félix. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Wang, Mingxun. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Aron, Allegra T.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Jagels, Annika. University of Munster; Alemania Fil: Tsugawa, Hiroshi. RIKEN Center for Sustainable Resource Science; Japón Fil: Rainer, Johannes. University of Lübeck; Italia Fil: Garcia-Aloy, Mar. University of Lübeck; Italia Fil: Dührkop, Kai. Universitat Jena; Alemania Fil: Korf, Ansgar. University of Munster; Alemania Fil: Pluskal, Tomáš. Czech Academy of Sciences; República Checa Fil: Kameník, Zdeněk. Czech Academy of Sciences; República Checa Fil: Jarmusch, Alan K.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Caraballo Rodríguez, Andrés Mauricio. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Weldon, Kelly. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Nothias Esposito, Melissa. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Aksenov, Alexander A.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Bauermeister, Anelize. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Albarracín Orio, Andrea Georgina. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Grundmann, Carlismari O.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Vargas, Fernando. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Koester, Irina. University of California at San Diego; Estados Unidos Fil: Gauglitz, Julia M.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Gentry, Emily C.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Hövelmann, Yannick. University of Munster; Alemania Fil: Kalinina, Svetlana A.. University of Munster; Alemania Fil: Pendergraft, Matthew A.. University of California at San Diego; Estados Unidos Fil: Panitchpakdi, Morgan W.. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Tehan, Richard. Oregon State University; Estados Unidos Fil: Le Gouellec, Audrey. Universite Grenoble Alpes; Francia. Centre National de la Recherche Scientifique; Francia Fil: Aleti, Gajender. University of California at San Diego; Estados Unidos Fil: Mannochio Russo, Helena. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos Fil: Arndt, Birgit. University of Munster; Alemania Fil: Hübner, Florian. University of Munster; Alemania Fil: Hayen, Heiko. University of Munster; Alemania Fil: Zhi, Hui. University of California at San Diego; Estados Unidos Fil: Raffatellu, Manuela. University of California at San Diego; Estados Unidos Fil: Prather, Kimberly A.. University of California at San Diego; Estados Unidos Fil: Aluwihare, Lihini I.. University of California at San Diego; Estados Unidos Fil: Böcker, Sebastian. Friedrich-Schiller-University, Jena; Alemania Fil: McPhail, Kerry L.. State University of Oregon; Estados Unidos Fil: Humpf, Hans-Ulrich. University of Munster; Alemania Fil: Karst, Uwe. University of Munster; Francia Fil: Dorrestein, Pieter. University of California at San Diego. Skaggs School of Pharmacy & Pharmaceutical Sciences. Collaborative Mass Spectrometry Innovation Center; Estados Unidos

Made available in DSpace on 2021-06-25T10:45:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-25 Proper chromatographic methods may reduce the challenges inherent in analyzing natural product extracts, especially when utilizing hyphenated detection techniques involving mass spectrometry. As there are many variations one can introduce during chromatographic method development, this can become a daunting and time-consuming task. To reduce the number of runs and time needed, the use of instrumental automatization and commercial software to apply Quality by Design and statistical analysis automatically can be a valuable approach to investigate complex matrices. To evaluate this strategy in the natural products workflow, a mixture of nine species from the family Malpighiaceae was investigated. By this approach, the entire data collection and method development procedure (comprising screening, optimization, and robustness simulation) was accomplished in only 4 days, resulting in very low limits of detection and quantification. The analysis of the individual extracts also proved the efficiency of the use of a mixture of extracts for this workflow. Molecular networking and library searches were used to annotate a total of 61 compounds, including O-glycosylated flavonoids, C-glycosylated flavonoids, quinic/shikimic acid derivatives, sterols, and other phenols, which were efficiently separated by the method developed. These results support the potential of statistical tools for chromatographic method optimization as an efficient approach to reduce time and maximize resources, such as solvents, to get proper chromatographic conditions. NuBBE Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP) Collaborative Mass Spectrometry Innovation Center Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San Diego Faculty of Pharmaceutical Sciences of Ribeirão Preto Department of Physics and Chemistry University of São Paulo Max Planck Institute of Molecular Plant Physiology Biomedical Sciences Institute University of São Paulo Department of Biological Sciences Lamol Lab Feira de Santana State University (UEFS) NuBBE Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)

Made available in DSpace on 2020-12-12T01:51:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-11-01 Technological advances have contributed to the evolution of the natural product chemistry and drug discovery programs. Recently, computational methods for nuclear magnetic resonance (NMR) and mass spectrometry (MS) have speeded up and facilitated the process of structural elucidation even in high complex biological samples. In this chapter, the current computational tools related to NMR and MS databases and spectral similarity networks, as well as their applications on dereplication and determination of biological biomarkers, are addressed. Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), Av. Prof. Francisco Degni, 55 Nucleus of Research in Natural Products and Synthetics Dep. Physics and Chemistry Faculty of Pharmaceutical Sciences of Ribeirão Preto São Paulo University Dept. Biology/CEIS Institute of Biosciences of Rio Claro São Paulo State University (UNESP), Av. 24A n.1515 Medway Metabonomics Research Group University of Greenwich (UoG) Nuclei of Bioassays Biosynthesis and Ecophysiology of Natural Products (NuBBE) Department of Organic Chemistry Institute of Chemistry São Paulo State University (UNESP), Av. Prof. Francisco Degni, 55 Dept. Biology/CEIS Institute of Biosciences of Rio Claro São Paulo State University (UNESP), Av. 24A n.1515

Made available in DSpace on 2020-12-11T10:26:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 INCT Program [INCT-BioNat] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Centre for Scientific Computing (NCC/GridUNESP) of Sao Paulo State University (UNESP) Ethnopharmacological relevance: Croton floribundus Spreng. (Euphorbiaceae), popularly known as Capixingui, stands out due to its widespread use in traditional medicine to treat wounds, syphilis, hemorrhoids, eye diseases and as a purgative. Aim of the study: To characterize clerodanes diterpenes from C. floribundus and to evaluate the effects of the fraction and diterpenes (1-5) on inhibition of nitrite production. Materials and methods: The hydroethanolic root extract of C. floribundus was fractionated on a solid phase extraction column to obtain the fraction named Fr80%. From this, five compounds were obtained and characterized. The absolute configuration of compound 1 was determined by a combination of electronic and vibrational circular dichroism spectroscopies. Additionally, compounds 1-5 were evaluated for their inhibitory effects on nitrite production induced by lipopolysaccharide (LPS) in RAW 264 macrophage cell. Results: Five clerodane diterpenoids were characterized, and the absolute stereochemistry of 1 was established as 3R,4R,5R,8R,9R,10S,12S. The IC50 values obtained through inhibition of nitrite production were 28.52 +/- 2.21 mu M (1), 40.26 +/- 2.79 mu M (2), 25.47 +/- 2.16 mu M (3), 35.78 +/- 2.93 mu M (4) and 40.58 +/- 4.78 mu M (5). In the tested concentrations, the samples presented low toxicity in macrophages. Conclusions: Four new diterpenes were characterized from C. floribundus, these being croflorins A-D (1-4) and a known halimane (5). These compounds exhibited inhibitory effect on nitrite production. Sao Paulo State Univ, Inst Chem, BR-14800060 Araraquara, SP, Brazil Fluminense Fed Univ, Inst Chem, BR-24020141 Niteroi, RJ, Brazil Univ Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, BR-01049010 Araraquara, SP, Brazil Sao Paulo State Univ, Inst Chem, BR-14800060 Araraquara, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, BR-01049010 Araraquara, SP, Brazil INCT Program [INCT-BioNat]: 465637/2014-0 INCT Program [INCT-BioNat]: 2014/50926-0 FAPESP: 2013/07600-3 FAPESP: 2014/25222-9 FAPESP: 2017/19870-6 CAPES: 001 CAPES: 88887.313278/2019-00 CNPq: 142286/2016-8 CNPq: 142014/2018-4 FAPESP: 2017/17098-4 FAPESP: 2019/04381-5 FAPESP: 2017/18807-9

Structure elucidation is an important and sometimes time-consuming step for natural products research. This step has evolved in the past few years to a faster and more automated process due to the development of several computational programs and analytical techniques. In this paper, the topics of NMR prediction and CASE programs are addressed. Furthermore, the elucidation of natural peptides is discussed.

Benznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite and with low toxicity. Silent information regulator 2 (Sir2) enzymes, or sirtuins, have emerged as attractive targets for the development of novel antitrypanosomatid agents. In the present work, we evaluated the inhibitory effect of natural compounds isolated from cashew nut (Anacardium occidentale, L. Anacardiaceae) against the target enzymes TcSir2rp1 and TcSir2rp3 as well as the parasite. Two derivates of cardol (1, 2), cardanol (3, 4), and anacardic acid (5, 6) were investigated. The two anacardic acids (5, 6) inhibited both TcSir2rp1 and TcSir2rp3, while the cardol compound (2) inhibited only TcSir2rp1. The most potent sirtuin inhibitor active against the parasite was the cardol compound (2), with an EC50 value of 12.25 &micro, M, similar to that of benznidazole. Additionally, compounds (1, 4), which were inactive against the sirtuin targets, presented anti-T. cruzi effects. In conclusion, our results showed the potential of Anacardium occidentale compounds for the development of potential sirtuin inhibitors and anti-Trypanosoma cruzi agents.

Made available in DSpace on 2018-12-11T17:35:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Niedenzuella multiglandulosa is a plant species known for having high toxicity and to cause death in cattle and sheep, promoting economic losses in Brazilian trade balance difficult to estimate. This work aims to evaluate the potential of thermoanalytical techniques (TG–DSC, TG-FTIR) and FTIR to identify compositional differences between the powder samples and methanolic extracts of young and old leaves. The TG–DSC profile for young and old leaves powder and extract presented some differences, mainly in the fourth mass loss step, that was attributed to the greater content of tannins in old leaves as also evidenced by FTIR. The cyclic DSC and TG curves showed that the leaves samples are highly hygroscopic, adsorbing water vapor even from the controlled humidity atmosphere. This characteristic thermal behavior can be useful for sample identification and characterization. Instituto de Química Universidade Estadual Paulista (Unesp) Faculdade de Ciências Universidade Estadual Paulista (Unesp) Instituto de Química Universidade Estadual Paulista (Unesp) Faculdade de Ciências Universidade Estadual Paulista (Unesp) CNPq: 152341/2015-2 FAPESP: 2013/07600-3 CNPq: 2014/465637-0 FAPESP: 2014/50926-0 FAPESP: 2017/14936-9 CNPq: 421469/2016-1

4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.