Molecular docking study on curcumin and its derivatives as inhibitors of BACE1 in the treatment of Alzheimer's disease

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder, and it is the main cause of dementia in the elderly. At present, no proper cure is available to stop the progression of AD. The neuronal damage in AD is due to the deposition of β-amyloid peptide and tau protein within the brain. Curcumin a curry spice has several beneficial activities such as antioxidant, antimicrobial, anti-inflammatory, and chemotherapeutic properties. Aims and Objectives: The main objective was to perform molecular docking of curcumin and its derivatives with BACE1 to determine its binding efficacy and the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the selected curcumin derivatives. Materials and Methods: Three-dimensional structure of the BACE1 was retrieved from RCSB database in protein data bank format. Total 200 ligand derivatives of curcumin were generated using the software advanced chemistry development/ChemSketch. The rapid virtual screening of the compounds was performed using the docking tool iGEMDOCK version 2.0. The ligands with low binding energy were selected and were analyzed for the drug-relevant properties. The final docking of the ligands was performed using the software AutoDock 4.0, based on the drug-like properties and the binding affinity. Results: Among the four ligands, based on the drug-likeness, the ligand (6Z)-1-(4-hydroxy-3-methoxy-2-nitrophenyl)-7-(4-hydroxy-3-methoxyohenyl) hepta-1,6-diene-3, 5-dione was the best. It had excellent binding energy with good ADMET properties. Conclusion: In this study, using the molecular docking method, a new compound has been identified to inhibit BACE1. This compound can be an effective drug candidate for controlling AD.