VII Simposio Internacional de Química 2019 "SIQ 2019" -VII Conferencia "Ciencias Químicas"

VII Simposio Internacional de Química 2019

SIQ 2019

VII Conferencia "Ciencias Químicas"

IDENTIFICATION OF MULTI-TARGET COMPOUNDS FOR TREATMENT OF ALZHEIMER'S DISEASE. MOLECULAR DYNAMICS STUDIES.

Resumen [ES]

Alzheimer`s disease (AD) is an irreversible, neurodegenerative and multifactorial brain disorder that slowly destroys memory and thinking skills. Several target proteins contributing to its aetiology. Different targets of these disease include amyloid-beta peptide (Aβ), APP pathogenic cleavage, cholinergic system and neurotransmitter. Thus, disease-modifying treatments for AD must interfere with the pathogenic steps responsible for each of the clinical symptoms. In these work, we use docking and molecular dynamics (MD) simulations in three different protein system with a patented data set of ligands derived from naphthalene. Virtual screening calculations were done to predict the potential interaction sites between Aβ, acetyl-cholinesterase and γ-secretase whit the ligand data base. MD simulations and Linear Interaction Energy (LIE) method were used to estimate the stability of the formed protein-ligand complex and the binding interaction energy. Three compounds were identified as lead and the simulations showed that hydrophobic and some polar interactions stabilize the protein-ligand complex formation. All these studies suggest that these three ligands could be used as potential multi-target-directed-ligand in the treatment of Alzheimer`s disease.

Resumen [EN]

Alzheimer`s disease (AD) is an irreversible, neurodegenerative and multifactorial brain disorder that slowly destroys memory and thinking skills. Several target proteins contributing to its aetiology. Different targets of these disease include amyloid-beta peptide (Aβ), APP pathogenic cleavage, cholinergic system and neurotransmitter. Thus, disease-modifying treatments for AD must interfere with the pathogenic steps responsible for each of the clinical symptoms. In these work, we use docking and molecular dynamics (MD) simulations in three different protein system with a patented data set of ligands derived from naphthalene. Virtual screening calculations were done to predict the potential interaction sites between Aβ, acetyl-cholinesterase and γ-secretase whit the ligand data base. MD simulations and Linear Interaction Energy (LIE) method were used to estimate the stability of the formed protein-ligand complex and the binding interaction energy. Three compounds were identified as lead and the simulations showed that hydrophobic and some polar interactions stabilize the protein-ligand complex formation. All these studies suggest that these three ligands could be used as potential multi-target-directed-ligand in the treatment of Alzheimer`s disease.

Sobre el ponente

Alberto Benomo Martínez

MsC. Alberto Benomo Martínez

Centro de Neurociencias de Cuba Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
MsC. Alberto Benomo Martínez
Dr. yoanna maría álvarez
Dr. marquiza sablón
Dr. luis alberto montero
Dr. chryslaine rodriguez
Dr. belinda sanchez
Dr. arvi rauk
Palabras clave
acetyl-cholinesterase
alzheimer`s
amyloid-beta
γ-secretase