Aplicação da RMN no estudo das interações entre toxinas urêmicas e a albumina humana

Orientador: Prof. Dr. Andersson BarisonCoorientador: Prof. Dr. Guilherme Lanzi SassakiTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Exatas, Programa de Pós-Graduação em Química. Defesa : Curitiba, 22/04/2019Inclui referências: p. 76-86Resumo: A doença renal crônica (DRC) é uma síndrome caracterizada pela redução progressiva da capacidade de filtração glomerular do organismo. Esse processo causa o acúmulo de diversos compostos orgânicos que através de reações e interações com as proteinas presentes no organismo podem causar danos em vários tecidos e órgãos. O presente estudo teve como finalidade empregar a ressonância magnética nuclear (RMN) aliada a calorimetria de titulação isotérmica (ITC) na avaliação das interações intermoleculares das toxinas urêmicas p-cresil sulfato (PCS) e indoxil sulfato (IS) com a proteína albumina sérica humana (HSA). Dessa forma, o experimento de RMN STD foi empregado para realizar o mapeamento dos epítopos dos ligantes e a determinação das constantes de dissociação de ambas as toxinas, bem como avaliar a influência da temperatura e da força iônica nessas interações. Além disso, foi realizado o ensaio de competição entre o PCS e o diazepam (inibidor do sítio II da HSA). O mapeamento dos epítopos através do experimento de RMN STD mostrou que os hidrogênios H-3/5 e H-5 do PCS e IS, respectivamente, são os que apresentam maior proximidade com o sítio de ligação da proteína. Através da determinação das constantes de dissociação (PCS: Kd = 6,5 mM e 4,8 mM a 25 ºC) foi observada uma afinidade moderada de ambas as toxinas com a HSA purificada revelando a maior afinidade da IS pela proteína. Também foi possível observar que a temperatura e a força iônica causam o aumento da interação do IS com a HSA purificada (Kd = 2,4 mM a 37 ºC e 2,3 mM a 25 ºC), respectivamente. Enquanto para o PCS o aumento da temperatura resultou na diminuição da interação com HSA (Kd = 8,5 mM a 37 ºC) e o aumento da força iônica não afetou essa interação (Kd = 6,8 mM a 25 ºC). Esses resultados sugerem que a HSA purificada pode ainda conter resquício de acetiltriptofanato de sódio e caprilato de sódio e que esses compostos afetam de formas distintas a interação das toxinas urêmicas com a HSA. Na ausência desses compostos, observou-se um aumento da afinidade de ambas as toxinas (PCS: Kd = 2,9 mM e IS: Kd = 3,1 mM a 25 ºC) com a HSA (? 99% de pureza), corroborando a hipótese de que a presença dos resquícios de acetiltriptofanato de sódio e caprilato de sódio interferem de modo que diminuem a afinidade do PCS e IS com HSA. O ensaio de competição indicou que o PCS tem afinidade pelo sítio II da HSA. Através dos experimentos de ITC foi possível a determinação dos parâmetros cinéticos e termodinâmicos dessas interações. Com relação aos dados termodinâmicos obtidos pelo ITC, foi observado que a ligação do PCS e IS com a HSA envolve interações eletrostáticas e hidrofóbicas. Além disso, observou-se que a interação desses compostos com a proteína é governada principalmente pela contribuição entálpica o que sugere a presença de ligações de hidrogênio ou interações de Van der Waals entre essas moléculas e a proteína. Dessa forma, o experimento de RMN STD aliado a ITC permitem o entendimento das forças que regem as interações de PCS e IS com a HSA e esses resultados podem auxiliar no desenvolvimento de estratégias terapêuticas para aumentar a remoção desses compostos do organismo dos pacientes acometidos pela DRC. Palavras-chave: RMN STD. ITC. Interações intermoleculares. Ligantes. Proteínas.Abstract: Chronic kidney disease (CKD) is a syndrome characterized by the progressive reduction of the body's glomerular filtration capacity. This process causes the accumulation of various organic compounds that, through reactions and interactions with proteins present in the body, can cause damage to various tissues and organs. This work intended to apply nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC) to evaluate the intermolecular interactions of uremic toxins p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with the protein human serum albumin (HSA). Therefore, the experiment of saturation-transfer difference (STD) NMR was adopted to perform epitopes mapping of ligands and determine dissociation constants of both toxins and the influence of temperature and ionic strength on these interactions. Besides, the competition assay between PCS and diazepam (site II inhibitor of HSA) was performed. Epitopes mapping using STD NMR experiment showed that hydrogens H-3/5 of PCS and H-5 of IS are the nearest to the protein binding site. A moderate affinity of both toxins with the purified HSA was revealed by determining dissociation constants (PCS: Kd = 6,5 mM and 4,8 mM, 25 ºC), suggesting a higher affinity of IS with the protein. Furthermore, it was possible to observe that the temperature and ionic strength cause increased interaction between IS and purified HSA (Kd = 2,4 mM at 37 ºC and 2,3 mM at 25 ºC, respectively). For PCS, temperature increment resulted in decreased interaction with HSA (Kd = 8,5 mM at 37 ºC), and the increase of ionic strength did not affect this interaction (Kd = 6,8 mM at 25 ºC). These results suggest that purified HSA may present some vestiges of sodium acetyltryptophanate and sodium caprylate, and those compounds affect in distinct ways interactions of uremic toxins with HSA. In the absence of those compounds, it was observed an increase in affinity for both toxins (PCS: Kd = 2,9 mM and IS: Kd = 3,1 mM at 25 ºC) with HSA (?99% of purity), corroborating with the hypothesis of the affinity decrease of PCS and IS with HSA interfered by the presence of vestiges of sodium acetyltryptophanate and sodium caprylate. The competition test indicated the affinity of PCS with site II of HSA. ITC experiments enabled the determination of the kinetic and thermodynamic parameters of those interactions. In relation to the thermodynamic data obtained by the ITC, it was observed that linkage of PCS and IS with HSA involves electrostatic and hydrophobic interactions. Therefore, it was indicated that the interaction of these compounds with the protein is controlled mainly by the enthalpic contribution that suggests the presence of hydrogen bonds or Van der Waals interactions between these molecules and the protein. Lastly, STD NMR experiment combined with ITC allows the knowledge of strengths that rule interactions of PCS and IS with HSA, and those results can assist the development of therapeutics strategies to increase the removal of these compounds from people committed by chronic kidney disease (CKD). Keywords: NMR STD. ITC. Intermolecular interactions. Ligands. Proteins

Ferramentas Computacionais para o ensino de Química: qual a opinião dos licenciandos sobre as atividades realizadas na disciplina?

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Ferramentas Computacionais para o Ensino de Química: qual a importância da disciplina na formação dos futuros professores?

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Xylopine Induces Oxidative Stress and Causes G 2

Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells

Aplicação da RMN no estudo das interações entre toxinas urêmicas e a albumina humana

Orientador: Prof. Dr. Andersson BarisonCoorientador: Prof. Dr. Guilherme Lanzi SassakiTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Exatas, Programa de Pós-Graduação em Química. Defesa : Curitiba, 22/04/2019Inclui referências: p. 76-86Resumo: A doença renal crônica (DRC) é uma síndrome caracterizada pela redução progressiva da capacidade de filtração glomerular do organismo. Esse processo causa o acúmulo de diversos compostos orgânicos que através de reações e interações com as proteinas presentes no organismo podem causar danos em vários tecidos e órgãos. O presente estudo teve como finalidade empregar a ressonância magnética nuclear (RMN) aliada a calorimetria de titulação isotérmica (ITC) na avaliação das interações intermoleculares das toxinas urêmicas p-cresil sulfato (PCS) e indoxil sulfato (IS) com a proteína albumina sérica humana (HSA). Dessa forma, o experimento de RMN STD foi empregado para realizar o mapeamento dos epítopos dos ligantes e a determinação das constantes de dissociação de ambas as toxinas, bem como avaliar a influência da temperatura e da força iônica nessas interações. Além disso, foi realizado o ensaio de competição entre o PCS e o diazepam (inibidor do sítio II da HSA). O mapeamento dos epítopos através do experimento de RMN STD mostrou que os hidrogênios H-3/5 e H-5 do PCS e IS, respectivamente, são os que apresentam maior proximidade com o sítio de ligação da proteína. Através da determinação das constantes de dissociação (PCS: Kd = 6,5 mM e 4,8 mM a 25 ºC) foi observada uma afinidade moderada de ambas as toxinas com a HSA purificada revelando a maior afinidade da IS pela proteína. Também foi possível observar que a temperatura e a força iônica causam o aumento da interação do IS com a HSA purificada (Kd = 2,4 mM a 37 ºC e 2,3 mM a 25 ºC), respectivamente. Enquanto para o PCS o aumento da temperatura resultou na diminuição da interação com HSA (Kd = 8,5 mM a 37 ºC) e o aumento da força iônica não afetou essa interação (Kd = 6,8 mM a 25 ºC). Esses resultados sugerem que a HSA purificada pode ainda conter resquício de acetiltriptofanato de sódio e caprilato de sódio e que esses compostos afetam de formas distintas a interação das toxinas urêmicas com a HSA. Na ausência desses compostos, observou-se um aumento da afinidade de ambas as toxinas (PCS: Kd = 2,9 mM e IS: Kd = 3,1 mM a 25 ºC) com a HSA (? 99% de pureza), corroborando a hipótese de que a presença dos resquícios de acetiltriptofanato de sódio e caprilato de sódio interferem de modo que diminuem a afinidade do PCS e IS com HSA. O ensaio de competição indicou que o PCS tem afinidade pelo sítio II da HSA. Através dos experimentos de ITC foi possível a determinação dos parâmetros cinéticos e termodinâmicos dessas interações. Com relação aos dados termodinâmicos obtidos pelo ITC, foi observado que a ligação do PCS e IS com a HSA envolve interações eletrostáticas e hidrofóbicas. Além disso, observou-se que a interação desses compostos com a proteína é governada principalmente pela contribuição entálpica o que sugere a presença de ligações de hidrogênio ou interações de Van der Waals entre essas moléculas e a proteína. Dessa forma, o experimento de RMN STD aliado a ITC permitem o entendimento das forças que regem as interações de PCS e IS com a HSA e esses resultados podem auxiliar no desenvolvimento de estratégias terapêuticas para aumentar a remoção desses compostos do organismo dos pacientes acometidos pela DRC. Palavras-chave: RMN STD. ITC. Interações intermoleculares. Ligantes. Proteínas.Abstract: Chronic kidney disease (CKD) is a syndrome characterized by the progressive reduction of the body's glomerular filtration capacity. This process causes the accumulation of various organic compounds that, through reactions and interactions with proteins present in the body, can cause damage to various tissues and organs. This work intended to apply nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC) to evaluate the intermolecular interactions of uremic toxins p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with the protein human serum albumin (HSA). Therefore, the experiment of saturation-transfer difference (STD) NMR was adopted to perform epitopes mapping of ligands and determine dissociation constants of both toxins and the influence of temperature and ionic strength on these interactions. Besides, the competition assay between PCS and diazepam (site II inhibitor of HSA) was performed. Epitopes mapping using STD NMR experiment showed that hydrogens H-3/5 of PCS and H-5 of IS are the nearest to the protein binding site. A moderate affinity of both toxins with the purified HSA was revealed by determining dissociation constants (PCS: Kd = 6,5 mM and 4,8 mM, 25 ºC), suggesting a higher affinity of IS with the protein. Furthermore, it was possible to observe that the temperature and ionic strength cause increased interaction between IS and purified HSA (Kd = 2,4 mM at 37 ºC and 2,3 mM at 25 ºC, respectively). For PCS, temperature increment resulted in decreased interaction with HSA (Kd = 8,5 mM at 37 ºC), and the increase of ionic strength did not affect this interaction (Kd = 6,8 mM at 25 ºC). These results suggest that purified HSA may present some vestiges of sodium acetyltryptophanate and sodium caprylate, and those compounds affect in distinct ways interactions of uremic toxins with HSA. In the absence of those compounds, it was observed an increase in affinity for both toxins (PCS: Kd = 2,9 mM and IS: Kd = 3,1 mM at 25 ºC) with HSA (?99% of purity), corroborating with the hypothesis of the affinity decrease of PCS and IS with HSA interfered by the presence of vestiges of sodium acetyltryptophanate and sodium caprylate. The competition test indicated the affinity of PCS with site II of HSA. ITC experiments enabled the determination of the kinetic and thermodynamic parameters of those interactions. In relation to the thermodynamic data obtained by the ITC, it was observed that linkage of PCS and IS with HSA involves electrostatic and hydrophobic interactions. Therefore, it was indicated that the interaction of these compounds with the protein is controlled mainly by the enthalpic contribution that suggests the presence of hydrogen bonds or Van der Waals interactions between these molecules and the protein. Lastly, STD NMR experiment combined with ITC allows the knowledge of strengths that rule interactions of PCS and IS with HSA, and those results can assist the development of therapeutics strategies to increase the removal of these compounds from people committed by chronic kidney disease (CKD). Keywords: NMR STD. ITC. Intermolecular interactions. Ligands. Proteins

A New Source of (R)-Limonene and Rotundifolone from Leaves of Lippia pedunculosa (Verbenaceae) and their Trypanocidal Properties

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-17T17:05:21Z No. of bitstreams: 1 Menezes L A new source....pdf: 240902 bytes, checksum: 6fac98c7e75cc4d38f9095f35e677c25 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-17T17:17:45Z (GMT) No. of bitstreams: 1 Menezes L A new source....pdf: 240902 bytes, checksum: 6fac98c7e75cc4d38f9095f35e677c25 (MD5)Made available in DSpace on 2017-08-17T17:17:45Z (GMT). No. of bitstreams: 1 Menezes L A new source....pdf: 240902 bytes, checksum: 6fac98c7e75cc4d38f9095f35e677c25 (MD5) Previous issue date: 2014FAPITEC/SE (Editais No 07/2009 and 10/2009), FAPESB, CNPq, FINEP, UFPR and CAPESUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilUniversidade Federal do Paraná. Departamento de Química. Curitiba, PR, BrasilUniversidade Federal do Paraná. Departamento de Química. Curitiba, PR, BrasilUniversidade Federal de Sergipe. Departamento de Química. Itabaiana, SE, BrasilInvestigation by GC-FID and GC-MS of the essential oil (LPOE) from the leaves of Lippia pedunculosa revealed, as the major compounds, the monoterpenes rotundifolone (71.7%) and (R)-limonene (21.8%). These two compounds and the minor constituent piperitenone (1.2%) were also isolated from the leaves and identified by spectrometric analysis. LPOE and isolated compounds were evaluated for their trypanocidal activity against epimastigote and trypomastigote forms of Trypanosoma cruzi. Significant results with IC50 values lower than 34.0 g.mL-1 were observed against these forms of T. cruzi for LPOE and isolated compounds. Rotundifolone was the most active compound with an IC50 lower than 10.0 g.mL-1 for both forms of T. cruzi. The effects of LPOE and isolated compounds were also evaluated in cultures of macrophages infected with T. cruzi. Treatment with (R)-limonene and rotundifolone caused a moderate reduction in the percentage of macrophages infected by T. cruzi and in the number of intracellular parasites at concentrations non-toxic to macrophages

Antitumor Properties of the Essential Oil From the Leaves of Duguetia gardneriana.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-07-10T12:11:59Z No. of bitstreams: 1 Rodrigues ACBC Antitumor....pdf: 142853 bytes, checksum: db7ecf9b40d453b0b76d913201aa845d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-07-10T13:39:36Z (GMT) No. of bitstreams: 1 Rodrigues ACBC Antitumor....pdf: 142853 bytes, checksum: db7ecf9b40d453b0b76d913201aa845d (MD5)Made available in DSpace on 2015-07-10T13:39:36Z (GMT). No. of bitstreams: 1 Rodrigues ACBC Antitumor....pdf: 142853 bytes, checksum: db7ecf9b40d453b0b76d913201aa845d (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Sergipe. Department of Chemistry. São Cristovão, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilFederal University of Sergipe. Department of Biology. São Cristovão, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Departamento de Propedêutica. Salvador, BA, BrasilFederal University of Amazonas. Department of Chemistry. Manaus, AM, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilDuguetia gardneriana, popularly known in the Brazilian northeast as “jaquinha”, is a species belonging to the family Annonaceae. The aim of this work was to assess the chemical composition and antitumor properties of the essential oil from the leaves of D. gardneriana in experimental models. The chemical composition of the essential oil was analyzed via gas chromatography-flame ionization detector and gas chromatography-mass spectrometry. In vitro cytotoxic activity was determined in cultured tumor cells, and in vivo antitumor activity was assessed in B16-F10-bearing mice. The identified compounds were β-bisabolene (80.99%), elemicin (8.04%), germacrene D (4.15%), and cyperene (2.82%). The essential oil exhibited a cytotoxic effect, with IC50 values of 16.89, 19.16, 13.08, and 19.33 μg/mL being obtained for B16-F10, HepG2, HL-60, and K562 cell lines, respectively. On the other hand, β-bisabolene was inactive in all of the tested tumor cell lines (showing IC50 values greater than 25 μg/ mL). The in vivo analysis revealed tumor growth inhibition rates of 5.37–37.52% at doses of 40 and 80mg/kg/day, respectively. Herein, the essential oil from the leaves of D. gardneriana presented β-bisabolene as the major constituent and showed cytotoxic and antitumor potential

Chemical Composition and Anti-Trypanosoma cruzi Activity of cruzi Activity of Essential Oils Obtained from Leaves of Xylopia frutescens and X. laevigata (Annonaceae)

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-11T16:22:43Z No. of bitstreams: 2 Silva TB Chemical composition....pdf: 965160 bytes, checksum: 3b2a7b231d5a93748e2b5b02eac7eaec (MD5) Silva TB Chemical composition....pdf: 965160 bytes, checksum: 3b2a7b231d5a93748e2b5b02eac7eaec (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-11T16:37:02Z (GMT) No. of bitstreams: 2 Silva TB Chemical composition....pdf: 965160 bytes, checksum: 3b2a7b231d5a93748e2b5b02eac7eaec (MD5) Silva TB Chemical composition....pdf: 965160 bytes, checksum: 3b2a7b231d5a93748e2b5b02eac7eaec (MD5)Made available in DSpace on 2016-05-11T16:37:02Z (GMT). No. of bitstreams: 2 Silva TB Chemical composition....pdf: 965160 bytes, checksum: 3b2a7b231d5a93748e2b5b02eac7eaec (MD5) Silva TB Chemical composition....pdf: 965160 bytes, checksum: 3b2a7b231d5a93748e2b5b02eac7eaec (MD5) Previous issue date: 2013Universidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilUniversidade Federal de Sergipe. Departamento de Biologia. São Cristóvão, SE, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilEssential oils from leaves of Xylopia frutescens (XFMJ) and two specimens of Xylopia laevigata (XLMC and XLSI) were obtained by hydrodistillation using a Clevenger-type apparatus, and analyzed by GC-MS and GC-FID. Sesquiterpenes dominated the essential oils. The main constituents of XFMJ were (E)-caryophyllene (24.8%), bicyclogermacrene (20.8%), germacrene D (17.0%), -elemene (7.9%), and (E)--ocimene (6.8%). XLMC contained significant quantities of germacrene D (18.9%), bicyclogermacrene (18.4%), -elemene (9.5%), -selinene (9.2%), (E)-caryophyllene (8.5%), germacrene B (5.7%) and -muurolene (5.7%), while germacrene D (27.0%), bicyclogermacrene (12.8%), (E)-caryophyllene (8.6%), -muurolene (8.6%), -cadinene (6.8%), and germacrene B (6.0%) were the main components of XLSI. The essential oils had trypanocidal activity against the Y strain of Trypanosoma cruzi, with IC50 values lower than 30 μg.mL-1 and 15 μg.mL-1 against epimastigote and trypomastigote forms of T. cruzi, respectively, and were also able to reduce the percentage in vitro of T. cruzi-infected macrophages and the intracellular number of amastigotes at concentrations that were non-cytotoxic to macrophage

Chemical composition and antiparasitic activity of essential oils from leaves of Guatteria friesiana and Guatteria pogonopus (Annonaceae)

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-08T12:23:12Z No. of bitstreams: 1 Meira CS Chemical composition and antiparasitic activity ....pdf: 688561 bytes, checksum: 72fe661700c8c547c3187657d5121de1 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-08T12:45:31Z (GMT) No. of bitstreams: 1 Meira CS Chemical composition and antiparasitic activity ....pdf: 688561 bytes, checksum: 72fe661700c8c547c3187657d5121de1 (MD5)Made available in DSpace on 2018-08-08T12:45:31Z (GMT). No. of bitstreams: 1 Meira CS Chemical composition and antiparasitic activity ....pdf: 688561 bytes, checksum: 72fe661700c8c547c3187657d5121de1 (MD5) Previous issue date: 2016Conselho Nacional de Desenvolvimento Científico e Tecnológico [grant number 301837/2015-5]; Fundação de Amparo à Pesquisa do Estado da Bahia [grant number PET0042/2013]; Programa de Apoio a Núcleos de Excelência [grant number PNX0002/2014].Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, Brasil / Universidade Federal do Paraná. Centro de NMR. Curitiba, PR, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, Brasil / Universidade de Campinas. Instituto de Química. Campinas, SP, BrasilUniversidade Federal de Amazonas. Instituto de Ciências Exatas. Departamento de Química. Manaus, AM, BrasilUniversidade Federal de Amazonas. Instituto de Ciências Exatas. Departamento de Química. Manaus, AM, BrasilUniversidade Federal de Sergipe. Departamento de Química. São Cristóvão, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilNatural products represent a valuable source for discovery of antiparasitic agents. Here, we describe the antiparasitic activity from essential oils extracted from leaves of Guatteria friesiana (EOGF) and Guatteria pogonopus (EOGP) (Annonaceae). The essential oils were obtained by hydrodistillation and analyzed by GC/MS and GC-FID. The sesquiterpenes are more abundant in both essential oils. G. friesiana are dominated by β-eudesmol (51.9%), γ-eudesmol (18.9%) andα-eudesmol (12.6%). The major compounds identified for EOGP were spathulenol (24.8%), γ-amorphene (14.7%) and germacrene D (11.8%). The essential oils demonstrated potent trypanocidal and antimalarial activities with values of IC50 lower than 41.3 μg/mL. EOGF also inhibits the proliferation of amastigotes. In addition, we identified significant ultrastructural alterations induced by the essential oils, especially in the cell membrane, Golgi complex, endoplasmatic reticulum and mitochondria. The results presented herein reinforce the potential of other members of this family for search of antiparasitic compounds