Title:Structure and Ligand Based Rational Drug Design for Bace-1 Inhibitors
VOLUME: 9 ISSUE: 1
Author(s):E. P. Semighini, Carlton A. Taft and C. H. T. P. Silva
Affiliation:Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. do Cafe s/n, Monte Alegre, 14040-903, Ribeirao Preto – Brasil.
Keywords:BACE-1, Alzheimer, virtual screening
Abstract:Alzheimer’s Disease (AD) is the major cause of senile dementia, flawing out 10% of 65 years old population
and 50% of 85 years old, globally. The major physiopathology of AD is the deposition of extracellular neuritic plaques in
memory related areas of the brain. These plaques are composed of the β-amyloid peptide resulting from the amyloidogenic
pathway, that starts with the β-secretase enzyme. BACE-1 (β-secretase 1) is considered one of the most promising
treatments of the disease. In this work, different molecular modeling and drug design techniques were used to design
novel inhibitors of BACE-1, starting from structures available in the Protein Data Bank. The results obtained from virtual
screening of compound libraries lead to 28 promising compounds, which were then evaluated by toxicity prediction,
pharmacokinetic properties and analysis of the binding modes in the catalytic site, resulting in 10 compounds with high
theoretical inhibition potential.
