Orientador: Prof. Dr. João Henrique Ghilardi Lago / Tese (doutorado) - Universidade Federal do ABC. Programa de Pós-Graduação em Ciência e Tecnologia/Química, 2016. / Diversas linhas de pesquisa em fitoquimica estao associadas a avaliacao de atividades biologicas visando o isolamento e caracterizacao de metabolitos ativos. Nesse contexto, foi observado que o oleo essencial, bem como os extratos das folhas de Nectandra leucantha (Lauraceae), ainda desconhecida do ponto de vista quimico, mostraram potencial antiparasitario, especialmente antileishmania e antitripanosoma. Sendo assim, o oleo essencial foi analisado por CG/FID e CG/EM permitindo a identificacao de 33 componentes, sendo o biciclogermacreno o majoritario (21,3 %). Os extratos hexanico e metanolico foram submetidos a fracionamento cromatografico, biomonitorado, frente a duas tecnicas cromatograficas diferentes (coluna aberta e em contracorrente), permitindo o isolamento de cinco neolignanas dos extratos: uma do tipo 3-3¡¦, desidrodieugenol (I) e quatro do tipo 3-O-4¡¦, desidrodieugenol B (II), 4,5-dimetoxi-3-[5'-metoxi-1'-(8'-propenil)4¡¦-fenoxi]-1-(8-propenil)benzeno (III), (S)-4-hidroxi,5-metoxi -1- [5'-metoxi-1'-(8'-propenil) 4¡¦-fenoxi]-1-(7-hidroxi-8-propenil) benzeno (IV) e (R)-4,5-dimetoxi-1-[5'-metoxi-1'-(8'-propenil)4¡¦fenoxi]-1-(7-hidroxi-8-propenil) benzeno (V), sendo III, IV e V ineditas. Alem disso, foi preparado o composto I-a, desidrodieugenol permetilado. As estruturas de todas as substancias descritas foram definidas atraves de metodos espectroscopicos e espectrometricos tais como, EM, RMN, UV, IV e DC. As substancias I-V e I-a, como os precursores, eugenol e metileugenol foram submetidos a avaliacao de suas atividades frente as formas tripomastigotas e amastigotas de Trypanosoma cruzi, promastigotas e amastigotas de Leishmania (L.) infantum e L (L.) donovani. Frente ao parasita T. cruzi, as ica do parasita, ergosterol. Desta maneira as substancias ativas encontradas neste estudo mostraram ser excelentes candidatos a desenvolvimento de farmacos visando a terapia da leishmaniose e doenca de Chagas, ja que se mostraram mais ativas e mais seletivas que os farmacos utilizados atualmente. / Several phytochemical researches are associated with evaluation of biological activities, aiming the isolation and characterization of active metabolites. In this context, it was observed that the essential oil and extracts from leaves of Nectandra leucantha (Lauraceae), specie unknown in the chemical point of view, displayed antiparasitical potential, specially antitrypanosomal and antileishmanial. Thus, essential oil was analysed by GC/FID and GC/MS allowing the identification of 33 compounds, in which bicyclogermacrene was present in higher amount (21.3%). The hexanic and methanolic extracts were subjected to a bioassay-guided chromatographic fractionation, using two different tecniques (open column and countercurrent chromatography), which afforded the isolation of five neolignans from extracts: one 3-3¡¦ neolignan type, dehydrodieugenol (I) and four 3-O-4¡¦ neolignan type, dehydrodieugenol B (II) and 4,5-dimethoxy-3-[5'-methoxy-1'-(8'-propenyl) 4¡¦-phenoxy]-1-(8-propenyl) benzene (III), (S)-4-hydroxy-5-methoxy-3-[5'-methoxy-1'-(8'-propenil) 4¡¦-phenoxy]-1-(7-hydroxy-8-propenyl) benzene (IV) and (R)-4,5-dimethoxy-3-[5'-methoxy-1'-(8'-propenyl)4¡¦-phenoxy]-1-(7-hydroxy-8-propenyl) benzene (V), which III, IV and V are described for the first time. Furthermore, the compound I-a, permethylated dehydrodieugenol was prepared. The structures of all described compounds were elucidated through spectroscopic and spectrometric methods, such as, MS, NMR, UV, IR and CD. Compounds I-V, I-a and precursors, eugenol and methyleugenol were subjected to evaluation of biological activities against trypomastigotes and amastigotes of T. cruzi and promastigotes and amastigotes of L. infantum and L. donovani. In respect of T. cruzi activities, compounally the cell death mechanism against T. cruzi parasites were evaluated for compounds I and I-a, suggesting direct action at parasites, probably related to interaction with the responsible compound of parsite cell membrance maintenance, ergosterol. Thus, the active compounds found in this study shown to be excellent candidates for drug development in the threatment of leishmaniasis and Chagas disease, as they were more active and more selective than drugs currently used.
| Identifer | oai:union.ndltd.org:IBICT/oai:BDTD:105723 |
| Date | January 2016 |
| Creators | Grecco, Simone dos Santos |
| Contributors | Lago, João Henrique Ghilardi, Cunha, Rodrigo Luiz Oliveira Rodrigues, Torrecilhas, Ana Claudia Trocoli, Silva, Dulce Helena Siqueira, Romoff, Paulete |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf, 289 f. : il. |
| Source | reponame:Repositório Institucional da UFABC, instname:Universidade Federal do ABC, instacron:UFABC |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=105723&midiaext=74127, http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=105723&midiaext=74126, Cover: http://biblioteca.ufabc.edu.brphp/capa.php?obra=105723 |
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