In Silico Search and Toxicology Prediction of Novel Potential β-Secretase Inhibitors in Alzheimers Disease

Author(s): Vinicius Barreto da Silva, Adriana Mieco Namba, Daniela Godoy Pantalena, Taina Ferreira do Prado, Carlos Henrique Tomich de Paula da Silva.

Journal Name:Current Bioactive Compounds

Volume 5 , Issue 2 , 2009

Abstract:

Alzheimers disease has become one of the most serious healthcare problems nowadays, where age is clearly the major risk factor. The pathology of the disease is characterized by the formation of senile plaques outside the neurons, which are composed, predominantly, by the β-amyloid (Aβ) peptide. Considering that β-secretase is an aspartyl protease involved in the cleavage of the amyloid precursor, the first step required for the formation of Aβ, becomes an attractive therapeutic target for drug design. A virtual screening approach based on flexible docking was applied in order to identify potential inhibitor candidates of β-secretase, since the docking method used here showed to be able to reproduce the binding modes of crystallographic complexes. After validation, ten potential inhibitors were selected and evaluated with respect to the analysis of toxicological groups. The most promising inhibitor candidate was analyzed in a molecular dynamics trajectory to reinforce, theoretically, the potential inhibitory activity. Overall results obtained here suggest that this novel potential β-secretase inhibitor could be a promising pharmaceutical for the Alzheimers disease treatment.

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Article Details

VOLUME: 5
ISSUE: 2
Year: 2009
Page: [119 - 127]
Pages: 9
DOI: 10.2174/157340709788452000
Price: $58