Molecular modeling and structure-activity relationships of acetylcholinesterase and inhibitors in Alzheimer's Disease

• Grant number: 08/07248-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2009
• End date: February 28, 2011
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Carlos Henrique Tomich de Paula da Silva
• Grantee: Jonathan Resende de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Alzheimer's disease is the most important cause of dementia in the elderly: affects 10% of the world's population aged around 65 and reaches about 50% of individuals over 85 years. The progression of symptoms of the disease is associated with structural changes at cholinergic synapses in certain brain regions and thus to decrease the potential for cholinergic neurotransmission. Thus, increasing the capacity of neurotransmission is the fundamental mechanism of the drugs used to treat the Alzheimer's disease. This is possible by inhibiting the enzyme acetylcholinesterase (AChE), which operates in the cholinergic synapses of the central and peripheral nervous system, responsible for interrupting the transmission of nerve impulse through the hydrolysis of acetylcholine.For this project, will be initially used different techniques of molecular modeling and molecular hybridization proposed as a strategy of rational drug design on the basis of the Acetilcolinesterase (AChE)inhibitors reported in the literature than those that have structures deposited in the PDB, including some that have been used to treat the Alzheimer's disease. The goal is to design and test new potential therapeutic inhibitors that target, in an attempt to obtain and optimize new prototypes as future drug candidates in Alzheimer's Mal. The goals extend to proposals for new potential prototypes, selected from databases of commercial compounds containing properties of drugs. The virtual screenings will be biased to structures of inhibitors already reported in the literature as well as the pharmacophore common to them, which will be modeled. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALMEIDA, Jonathan Resende de. Molecular modeling studies and structure-activity relationships of acetylcholinesterase inhibitors in Alzheimer\'s disease.. 2011. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.