Tese (doutorado)—Universidade de Brasília, Instituto de Física, 2009. / Submitted by Washington da Silva Chagas (washington@bce.unb.br) on 2011-04-08T22:01:47Z
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2009_AlexandreAdrianoNevesdePaula.pdf: 2060811 bytes, checksum: 3d83cdcea3d3a462702b9f2f3086db68 (MD5) / Neste trabalho apresentamos um estudo sobre novos candidatos a inibidores da acetilcolinesterase obtidos a partir de um lipídio fenólico não-isoprenóide do líquido da casca da castanha de caju (Anacardium occidentale). Foram investigados, através do cálculo de estrutura eletrônica, dois Padrões de Estrutura Molecular (PEM) derivados do cardanol: um composto por 15 moléculas construídas a partir do PEM2 com os grupos substituintes metila, acetila, N,N-dimetilcarbamoíla, N,N-dimetilamina, N,N-dietilamina, pirrolidina, piperidina e N-benzilamina e outro composto por 20 moléculas derivadas do PEM3 substituindo fragmentos que fariam interação com a serina200 (S200) e do triptofano84 (W84) pelos anéis de 5 e 6 membros. As propriedades eletrônicas, tais como energias (HOMO-1, HOMO, LUMO, LUMO+1 e derivados), distribuições de cargas (anel benzênico, oxigênio 56, carbono 11 e nitrogênio das aminas secundárias) entre outras, foram obtidas usando os níveis de cálculos RHF e B3LYP com os conjuntos de funções de base 6-31G, 6-31G(d), 6-31+G(d),6-311G(d,p) 6-311G(2d,p) e 6-311+G(2d,p). Os resultados obtidos revelam que os derivados do PEM2, formadas com as substituições acetila, N,N-dimetilformamida, N,N-dimetilamina e pirrolidina, são as estruturas que mais se correlacionam com o fármaco amplamente utilizado como inibidor da acetilcolinesterase contra a doença de Alzheimer (rivastigmina). Com relação aos derivados do PEM3 os compostos que melhor se correlacionam com a rivastigmina foram as estruturas PEM3-01, PEM3-03, PEM3-06 e PEM3-19. _________________________________________________________________________________ ABSTRACT / In this work is presented a study about new potential candidates of acetylcholinesterase
(AChE) inhibitors designed from cardanol, a non-isoprenoid phenolic
lipid of cashew Anacardium occidentale nut-shell liquid. From electronic structure
calculations were investigated two molecular structure models (PEM): the first is
formed by 15 molecules derivatives from the cardanol (PEM2) using the groups
methyl, acetyl, N,N-dimethylcarbamoyl, N,N-dimethylamine, N,N-diethylamine, piperidine,
pyrrolidine, and N,N-methylbenzylamine; while the second is formed by 20
molecules derivatives from cardanol (PEM3) substituting the fragments that interacts
with ser200 and W84 sites by rings with 5 and 6 species. Electronic properties,
such as, energies (HOMO, LUMO, HOMO-1, LUMO+1 and derivatives) and charge
distributions were performed at RHF and B3LYP levels using 6-31G, 6-31G(d),
6-31+G(d),6-311G(d,p) 6-311G(2d,p) and 6-311+G(2d,p) basis functions. The obtained
results indicated that the PEM2 structures with substitution by acetyl, N,Ndimethylcarbamoyl,
N,N-dimethylamine, and pyrrolidine groups PEM3 were better
correlated to rivastigmine and represent possible AChE inhibitors against Alzheimer
disease. In relation to PEM3 molecular structure model the compounds that presented
a significant contribution in the recognition by AChE were PEM3-01, PEM3-
03, PEM3-06 e PEM3-19.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unb.br:10482/7408 |
| Date | 31 July 2009 |
| Creators | Paula, Alexandre Adriano Neves de |
| Contributors | Martins, João Batista Lopes |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UnB, instname:Universidade de Brasília, instacron:UNB |
| Rights | info:eu-repo/semantics/openAccess |
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