SCREENING AND MOLECULAR DOCKING STUDIES OF CURCUMIN AND ITS DERIVATIVES AS INHIBITORS OF AMYLOID- β PROTEIN - A KEY PROTEIN IN ALZHEIMER'S DISEASE
Abstract
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Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disease. This disease is characterized by progressive cognitive deterioration
along with declining activities of the day to day and behavioral changes. One of the important pathogenesis in AD is the chronic inflammation of
neuron. Studies have demonstrated the associated inflammatory changes such as astrocytosis, microgliosis, and the presence of pro-inflammatory
components that accompany the deposition of amyloid-β (Aβ) peptide. In Alzheimer patients, a chronic inflammation occurs because of activated
macrophages and an increased amount of cell signaling proteins. Curcuma longa of Zingiberaceae family is cultivated spice in India and other Asian
countries. Turmeric has a high content of curcuminoids and is recognized for its broad spectrum of biological activities. Molecular docking studies
were performed by selecting various curcuminoids as Aβ inhibitors.
Methods: Docking studies help to understand the binding interactions of the protein with the ligands. Alzheimer's Aβ precursor(PDB ID: 1AAP) was
selected as the crucial protein involved in AD and curcuminoids were selected as ligands. Molecular properties and quantitative structure-activity
relationship (QSAR) model were calculated using Med Chem Designer and Build QSAR. Docking studies were performed using Autodock 4.0.
Results: Docking results indicate that curcuminoids can be considered as inhibitors of AAP as they interact with the active site region.
Conclusion: Docking analysis of auto dock binding energies and binding interactions of curcumin and its derivatives indicates that curcumin,
curcumin bis acetate, bisdemethoxy curcumin, [18F] fluoropropyl substituted curcumin and tetrahydrocurcumin can be considered as probable
inhibitors of AAP.
Keywords: Alzheimer's disease, Curcuma longa, Curcuminoids, Docking, Quantitative structure-activity relationship, Amyloid protein.
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