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Previous issue date: 2014-09-10 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Malaria is considered a non-contagious chronic evolution with episodic manifestations of acute character infectious disease, which afflicts millions of people in tropical and subtropical areas of the world. Vegetables represent a source of active molecules for various diseases, including malaria. Through phytochemical procedures, one can study the secondary metabolism of these plants where they hope to find new sources of treatment for malaria. The present study had as main objective to identify molecules derived from natural sources can inhibit the ATPase-Ca 2 + protein of Plasmodium falciparum (PfATP6). The molecular target was the model PfATP6 receiver, obtained by comparative modeling. Was performed using the program AutoDock Vina 1.1.2. screening in databases with the aim of selecting the 10 most promising ligands, with determination of the energies of affinity. Subsequently, tests with hydromethanolic and chloroform extracts of the species of Tul Cenostigma macrophyllum were performed. The patterns of agatisflavona and amentoflavone biflavonoids were analyzed by High Performance Liquid Chromatography for Detection Arrangement Diodes (HPLC-DAD) to identify the presence of these metabolites in the species. Validation of the chromatographic method took into account the parameters selectivity, linearity, precision, accuracy, limit of detection and limit of quantification. The results showed molecular next coupling energy variation among the 10 selected compounds (1 kcal / mol). With the results of the molecular coupling of the intermolecular interactions were studied and agatisflavona amentoflavone with PfATP6 receiver comparing them with the values obtained for thapsigargin. Since the energy values affinity the compounds amentoflavone -10.0 kcal / mol and agatisflavona -9.7 kcal / mol ortost?rico showed affinity for the receptor site of PfATP6, these interactions being supported by the nature of intermolecular interactions identified. By comparing the retention times and ultraviolet spectra (UV) of the standards and samples could be identified agatisflavona amentoflavone and biflavonoids the leaves and stem bark of C. macrophyllum. Quantification of agatisflavona biflavonoide ranged from 22.25 to 0.012 mg of agatisflavona / g dry plant and amentoflavone ranged from 20.63 to 0.02 mg of amentoflavone / g dry plant. The analysis of the parameters evaluated showed that the method was suitable for the analysis of agatisflavona and amentoflavone, performing in line with the specifications of the current legislation. It is noticed that the amentoflavone agatisflavona compounds and can act in PfATP6 receiver, directing further studies of interactions in biological target in perspective for malaria control. Thus, it is possible to suggest that there are natural compounds present in semiarid with possible antimalarial activity, wherein the molecular modeling tool associated with the phytochemical analysis can guide the identification of bioactive compounds, and therefore the development of new drugs. / A mal?ria ? considerada como uma doen?a infecciosa, n?o contagiosa de evolu??o cr?nica com manifesta??es epis?dicas de car?ter agudo, a qual aflige milh?es de pessoas nas zonas tropicais e subtropicais do globo. Os vegetais representam fonte de mol?culas ativas para diversas enfermidades, incluindo a mal?ria. Atrav?s de procedimentos fitoqu?micos, pode-se estudar o metabolismo secund?rio desses vegetais onde se esperam encontrar novas fontes de tratamento para a mal?ria. O presente estudo teve como objetivo geral identificar mol?culas oriundas de fontes naturais capazes de inibir a prote?na ATPase-Ca+2 do Plasmodium falciparum (PfATP6). O alvo molecular foi o modelo do receptor PfATP6, obtido por modelagem comparativa. Foi realizado atrav?s do programa AutoDock Vina 1.1.2. uma triagem em bancos de dados com o objetivo de selecionar os 10 ligantes mais promissores, com determina??o das energias de afinidade. Posteriormente, foram realizados testes com os extratos hidrometan?lico e clorof?rmico da esp?cie de Cenostigma macrophyllum Tul. Os padr?es dos biflavonoides agatisflavona e amentoflavona foram analisados por Cromatografia L?quida de Alta Efici?ncia por Detec??o de Arranjo de Diodos (CLAE-DAD) para identifica??o da presen?a destes metab?litos na esp?cie. A valida??o do m?todo cromatogr?fico levou em considera??o os par?metros seletividade, linearidade, precis?o, exatid?o, limite de detec??o e limite de quantifica??o. Os resultados de acoplamento molecular apresentaram varia??o energ?tica pr?xima entre os 10 compostos selecionados (1 kcal/mol). De posse dos resultados do acoplamento molecular foram estudadas as intera??es intermoleculares da agatisflavona e amentoflavona com o receptor PfATP6 comparando-os com os valores obtidos para a tapsigargina. Dado os valores de energia de afinidade, os compostos amentoflavona -10,0 Kcal/mol e agatisflavona -9,7 Kcal/mol apresentaram afinidade com o s?tio ortost?rico do receptor PfATP6, sendo essas intera??es sustentadas pela natureza das intera??es intermoleculares identificadas. Atrav?s da compara??o dos tempos de reten??o e espectros de Ultra Violeta (UV) dos padr?es e amostras foi poss?vel identificar os biflavonoides agatisflavona e amentoflavona nas folhas e casca do caule de C. macrophyllum. A quantifica??o do biflavonoide agatisflavona variou de 22,25 a 0,012 ?g de agatisflavona/g de planta seca e da amentoflavona variou de 20,63 a 0,02 ?g de amentoflavona/g de planta seca. A an?lise dos par?metros avaliados demonstrou que o m?todo foi adequado para a an?lise da agatisflavona e amentoflavona, apresentando-se em conson?ncia com as especifica??es da legisla??o vigente. Percebe-se que os compostos amentoflavona e agatisflavona podem atuar no receptor PfATP6, direcionando novos estudos de intera??es nesse alvo biol?gico na perspectiva de controle da mal?ria. Desta forma ? poss?vel sugerir que existem compostos naturais presente no semi?rido com poss?vel atividade antimal?rica, no qual a ferramenta da modelagem molecular associada ?s analises fitoqu?micas pode guiar na identifica??o de compostos bioativos e, por conseguinte no desenvolvimento de novos f?rmacos.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.uefs.br:8080:tede/105 |
| Date | 10 September 2014 |
| Creators | Santos, Elis?ngela |
| Contributors | Brand?o, Hugo Neves |
| Publisher | Universidade Estadual de Feira de Santana, Mestrado Acad?mico em Recursos Gen?ticos Vegetais, UEFS, Brasil, DEPARTAMENTO DE CI?NCIAS BIOL?GICAS |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UEFS, instname:Universidade Estadual de Feira de Santana, instacron:UEFS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2441563959449389152, 600, 600, 600, 600, -6971480722008537872, -1634559385931244697, 2075167498588264571 |
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