Doutorado em Química
URI Permanente para esta coleção
Nível: início
Ano de início: 2014
Conceito atual na CAPES: 5
Ato normativo: Homologação da 85ª Reunião do CTC-ES, Parecer CNE/CES nº 163/2005.
Processo nº 23001.000081/2005-56 do Ministério da Educação.
Publicado no DOU 28/07/2005, seção 1, página 11)
Periodicidade de seleção: Anual
Área(s) de concentração: Química
Url do curso: https://quimica.vitoria.ufes.br/pt-br/pos-graduacao/PPGQ/detalhes-do-curso?id=956/a>
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Navegando Doutorado em Química por Assunto "Alcaloides"
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- ItemAlcaloides dos bulbos das espécies Griffinia gardneriana (Herb.) Ravenna e Habranthus itaobinus Ravenna (amaryllidaceae): perfil químico e propriedades citotóxicas e genotóxicas(Universidade Federal do Espírito Santo, 2018-08-23) Cole, Eduardo Roberto; Borges, Warley de Souza; Lacerda Junior, Valdemar; Endringer, Denise Coutinho; Santos, Reginaldo Bezerra dos; Kuster, Ricardo Machado; Cunha Neto, ÁlvaroThe Amaryllidaceae family is widely distributed throughout the world, being considered one of the 20 most important families among which they present alkaloids in their composition, exhibiting antiviral, antimalarial, anticancer and anticholinesterase activities, among others. This work aims to perform a chemical study on alkaloids of Griffinia gardneriana and Habranthus itaobinus bulbs, belonging to this family, to evaluate its cytotoxic and genotoxic properties and the role of caspase-3 as a molecular mediator of apoptosis induced by these compounds. Fractions enriched in alkaloids obtained from G. gardneriana and H. itaobinus bulbs were initially subjected to gas chromatography coupled to mass spectrometry (GC-MS) and then fractionated by different chromatographic techniques, such as molecular exclusion chromatography, column chromatography and preparative thin layer chromatography. The isolation and identification of the alkaloids was done by means of high performance liquid chromatography and mono- and bidimensional nuclear magnetic resonance, in addition to circular dichroism. Studies were carried out to evaluate the cytotoxicity of the enriched fractions by the MTT method using the OVCAR-3, J774 and L929 cell lines. In addition, the in vitro cytotoxicity and genotoxicity of the alkaloids isolated (through the MTT assay and micronucleus test) using tumoral (HepG2, MCF- 7, A549) and normal (L929, CHO-1-15) cell lines. In parallel, a study was developed to evaluate the correlation of the results obtained in the cytotoxicity assays by MTT and cytometry by image analysis. Molecular docking studies were performed to evaluate the free binding energies between the alkaloids isolated with the caspase-3 protein, described in the literature as the probable site of action of these compounds, also being calculated the theoretical inhibition constant, Ki. The GC-MS result of the enriched fractions evidenced the presence of only one alkaloid in G. gardneriana and five in H. itaobinus. Seven alkaloids of Amaryllidaceae, belonging to different type skeletons, all of them already well characterized in the literature, are some common ones to the two species (trisphaeridine and pretazettine), whereas others present only in G. gardneriana (lycorine and sanguinine) or in H. itaobinus (tazettine, 11- hydroxyvitattine and 2-a-7-dimethoxyhomolycorine). All enriched fractions showed cytotoxic action in the tested methods, but for the alkaloids isolated 11-hydroxyvitattine and 2-a-7-dimethoxyhomocolycorine were not cytotoxic, whereas tazettine, trisphaeridine and sanguinine presented activity only against the fibroblastic lineage. Lycorine and pretazettine were 10 to 30 times more cytotoxic than the other alkaloids, being active also for the cancerous lines, exhibiting time-dependent and concentration action, besides being genotoxic and able to promote the apoptosis via caspase-3. This result corroborates the data obtained in the docking studies in which these two compounds were among those with the highest binding affinity values.
- ItemEstudo fitoquímico de Hippeastrum diniz-cruziae Dutilh & Semir e Hippeastrum glaucescens (Mart.) Herb. (Amaryllidaceae)(Universidade Federal do Espírito Santo, 2019-08-28) Santos, Vanessa Dias dos; Borges, Warley de Souza; https://orcid.org/0000000344751028; http://lattes.cnpq.br/9742402285970429; https://orcid.org/; http://lattes.cnpq.br/3852118255704584; Neto, Alvaro Cunha; https://orcid.org/; http://lattes.cnpq.br/7448379486432052; Franca, Hildegardo Seibert; https://orcid.org/; http://lattes.cnpq.br/1284874997224988; Kuster, Ricardo Machado; https://orcid.org/0000000289615348; http://lattes.cnpq.br/4149814906786366The interest in the study of the Amaryllidaceae family is related by yours relevant chemical and biological potential that has presented over the years. The objective of this work is the isolation and characterization of alkaloids present in two Brazilian species, Hippeastrum diniz-cruziae (leaves, bulbs and roots) and Hippeastrum glaucescens (bulbs). Initially, an acid-base extraction was performed in the methanolic extracts and liquid-liquid partition of the vegetal parts, obtaining the acid AcOEt and alkaloid enriched fractions. These extracts were analyzed by GC-MS and indicated to Hippeastrum diniz-cruziae 39 known alkaloids and 24 unidentified compounds. For Hippeastrum glaucescens 12 known alkaloids and 9 unknown compounds were identified. These extracts were subjected to various chromatographic separation techniques in order to isolate and purify these compounds. As a result, 5 Hippeastrum diniz-cruziae alkaloids were isolated: cruzinine (I), 7-deoxy-narciclasine (II), licoryne (III), pseudolycorine (IV) and ungiminorine (V), with cruzinine being an unpublished alkaloid of the type homolicorin, elucidated by GC-MS, one and two-dimensional NMR, Circular Dichroism and, mainly, X-ray Crystallography. This compound presented a unique characteristic within Amaryllidaceae alkaloids, evidenced by the stereochemistry of positions H-1 and H-10b. Fractions of Hippeastrum glaucescens resulted in 20 alkaloids: 2α-7-dimethoxyhomolicorine N-oxide (VI), 7-Methoxy-O-methylillorenine N oxide (VII), Candimine N-oxide (VIII), N-oxide albamaculine (IX), 2α methoxyhomolycorine (XX), 2α-hydroxyhomolycorine (XXI), albomaculine (XXII), 2α hydroxyalbomaculine (XIII), 2α, 7-dimethoxyhomolycorine (XIV), 7-Methoxy-O methyllicorine (XV), candimine (XVI), hyppeastrine (XVII), haemantidine (XVIII), 6 epihaemantidine (XIX), 11-hydroxyvitatine (XX), tazetine (XXI), pretazetine (XXII), 3 epimachrine (XXIII), trisfaeridine (XXIV) and ismine (XXV), compounds (XI), (XVIII), (XIX) and (XXII) being obtained in three mixtures. The compounds (VI), (VII) and (VIII) were isolated for the first time in this study, being identified by 1H NMR and high resolution masses. for the compound (VII) also high resolution masses. Previous studies of Hippeastrum glaucescens have indicated relevant alkaloid and biological potential, with potential inhibitory enzyme acetylcholinesterase. For Hippeastrum diniz-cruziae this is the first phytochemical study performed, and its previous report has reported its high moebicide power and low toxicity. In this sense, this evidence 26 gives great relevance in the continuation of the respective chemical and biological studies with the respective species.