S?ntese e avalia??o da atividade anticolinester?sica de novos derivados do produto natural harmana

• Ano de defesa: 2013
• Autor(a) principal: Nogueira, Marcela Cristina Oliveira
• Orientador(a): Rumjanek, Victor Marcos
• Banca de defesa: Rumjanek, Victor Marcos, Chaves, Douglas Siqueira de Almeida, Nascimento, Cl?udia Jorge do
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal Rural do Rio de Janeiro
• Programa de Pós-Graduação: Programa de P?s-Gradua??o em Qu?mica
• Departamento: Instituto de Ci?ncias Exatas
• País: Brasil
• Palavras-chave em Português: Doen?a de Alzheimer; ? -carbolina; colinesterase; cin?tica enzim?tica
• Área do conhecimento CNPq: Qu?mica
• Link de acesso: https://tede.ufrrj.br/jspui/handle/jspui/3225

The increase in life expectancy is a worldwide occurrence that shows the relative success of public health politics, and Brazil is among the countries where people are living longer and in better physical health. However, the increase in life expectancy has a negative effect: the appearance of degenerative diseases typical of old age, including several forms of dementia, such as Alzheimer?s Disease (AD) that is certainly the most important. It is an irreversible and progressive disease characterized by neuronal deterioration that results in loss of cognitive functions such as memory, communication skills, judgment and reasoning. Donepezil, rivastigmine and galantamine are medicines used for the treatment of AD and act reversibly inhibiting acetylcholinesterase (AChE). Evidences suggest that the enzyme butyrylcholinesterase (BChE), closely related to AChE, plays a significant role in AD because it is involved in neural functions such as cholinergic co-regulation and non-cholinergic neurotransmission. The aim of this research is to provide new substances with anticholinesterase action by using ?-carboline derivatives from the natural product harmane and carry out a kinetic study to determine the inhibition profile of the enzymes AChE e BChE, which could help in the discovery of new compounds which could be useful in the treatment of AD. Firstly, a screening was carried out with seven ?-carboline derivatives. In a second stage, a kinetic investigation, employing Ellman?s method, was carried out with these compounds and all of them presented high anticholinesterase action for both AChE and BChE. All seven derivatives presented a non-competitive reversible inhibition.