Molecular Docking Study of Certain Plant Alkaloid Derivatives as Inhibitors of Various Drug Targets of Alzheimer’s Disease
Rithvik Ganesh1 and Iyanar Kannan21Rice Middle School, 8500 Gifford Dr, Plano, TX 75025, USA.
2Department of Microbiology Tagore Medical College and Hospital The Tamilnadu Dr. MGR Medical University Rathinamangalam, Chennai – 600127, India.
Corresponding Author E-Mail: dr.ikannan@tagoremch.com
Abstract: Alzheimer’s disease is a deadly form of dementia, and can greatly affect the way a person can think and behave. It is the sixth leading cause of death in the US alone. Clusters of Beta-Amyloid (Plaques) and twisted tangles of a protein called Tau (Tangles) are the primary cause of Alzheimer’s disease, as noted by Alois Alzheimer in 1906. Plaques and Tangles can block cell-to-cell signaling and disintegrate the cell transport system. The 3-dimensional structure of three drug targets, Beta-secretase 1, Cholinesterase, and Tau Protein kinase were retrieved from the RCSB PDB database. A total of 150 derivatives of Curcumin, Bacopaside IV, and Ginkgolide B were generated using the ACD ChemSketch software. These files were then converted to the Brookhaven protein data bank file using the OpenBabel software. Preliminary docking studies were then performed using the iGEMDOCK v2.0 software. All the prepared ligands were then tested for drug-likeliness properties using the DruLiTo and admetSAR softwares. Finally, compounds with good fit and drug likeliness were subjected to final docking with the AUTODOCK VINA software. In this study, the ligand with the name 8-(1-fluoro-2-methylpropan-2-yl)-6,12,17-trihydroxy-16-methyl-2,4,14,19-tetraoxahexacyclononadecane-5,15,18-trione is found to be a good inhibitor of 3 well-known drug targets. This is an effective lead molecule that can be used in the treatment of Alzheimer’s disease. Plaques and Tangles are major causes for Alzheimer’s disease. The novel lead molecule identified in this study is an inhibitor of these virulence factors and thus can be effective in controlling Alzheimer’s disease.
Keywords: Alzheimer’s disease; Beta-secretase 1; Cholinesterase; Ginkgolide B derivatives Molecular docking; Tau Protein kinase; Back to TOC