• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
10.11606/D.60.2011.tde-21032011-102116
Document
Author
Full name
Jonathan Resende de Almeida
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2011
Supervisor
Committee
Silva, Carlos Henrique Tomich de Paula da (President)
Giuliatti, Silvana
Yagui, Carlota de Oliveira Rangel
Title in Portuguese
Estudos de modelagem molecular e relação estrutura-atividade da acetilcolinesterase e inibidores em Mal de Alzheimer
Keywords in Portuguese
inibidores da acetilcolinesterase
Mal de Alzheimer
screening virtual.
Abstract in Portuguese
O Mal de Alzheimer é a causa mais importante de demência em idosos. A progressão dos sintomas da doença está associada com modificações estruturais nas sinapses colinérgicas em determinadas regiões cerebrais e, consequentemente, à diminuição do potencial de neurotransmissão colinérgica. Desta forma, o aumento da capacidade de neurotransmissão colinérgica constitui o mecanismo fundamental dos fármacos utilizados para o tratamento do Mal de Alzheimer. Atualmente, o único tratamento clínico eficaz para o Mal de Alzheimer (MA) é a utilização de inibidores da acetilcolinesterase (AChE). Os anticolinesterásicos são os fármacos mais promissores desenvolvidos até hoje, pois é a única classe terapêutica que mostrou melhora nos sintomas cognitivos do MA. Para esse projeto, foram utilizadas diferentes técnicas de modelagem molecular como estratégia de planejamento racional de fármacos, tendo como base os inibidores de Acetilcolinesterase (AChE) descritos na literatura além dos que possuem estruturas depositadas no PDB, incluindo alguns que já vêm sendo utilizados no tratamento do Mal de Alzheimer. O objetivo foi planejar e testar novos potenciais inibidores desse alvo terapêutico, na tentativa de obter e futuramente otimizar novos protótipos como futuros candidatos a fármacos em Mal de Alzheimer. Os objetivos estendem-se a propostas de novos potenciais protótipos, selecionados de bases de dados de compostos comerciais contendo propriedades de fármacos. Os screenings virtuais foram tendenciados às estruturas dos inibidores já reportados da literatura bem como ao padrão farmacofórico comum a eles, a ser modelado.
Title in English
Molecular modeling studies and structure-activity relationships of acetylcholinesterase inhibitors in Alzheimer's disease.
Keywords in English
acetylcholinesterase inhibitors
Alzheimers disease
virtual screening.
Abstract in English
Alzheimer's disease is the leading cause of dementia in the elderly. The progression of symptoms is associated with structural changes in cholinergic synapses in specific brain regions and consequentely to decrease the potential of cholinergic neurotransmission. Thus, the increased capacity of cholinergic neurotransmission is the fundamental mechanism of the drugs used to treat Alzheimer's disease. Currently, the only effective clinical treatment for Alzheimer's (MA) is the use of inhibitors of acetylcholinesterase (AChE). Cholinesterase inhibitors are the most promising drugs developed so far, it is the only therapeutic class that showed improvement in cognitive symptoms of MA. For this project, we used different techniques of molecular modeling as a strategy for rational design of drugs based on inhibitors of acetylcholinesterase (AChE) in the literature than those which have structures deposited in the PDB, including some that have already been used in the treatment Alzheimer's disease.The objective was to design and test new potential inhibitors of therapeutic target in attempts to obtain and optimize future new prototypes as future drug candidates in Alzheimer's disease. The goals extend to proposals from potential new prototypes, selected from databases of commercial compounds containing properties of drugs. The virtual screenings were trends to structures of the inhibitors already reported in the literature as well as the pharmacophoric pattern common to them, to be modeled.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2011-06-21
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
Centro de Informática de São Carlos
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2019. All rights reserved.