title: Use of ligand-based pharmacophore modeling and docking approach to find novel acetylcholinesterase inhibitors for treating Alzheimer's.
abstract: Alzheimer's disease is a neurological disorder in which the patient suffers from memory loss and impaired cognitive abilities. Though the main cause of the disease is not yet known, depletion of neurotransmitter at synaptic junctions, accumulation of insoluble beta amyloid plaques and neurofibrillary tangles are the main pathologies associated with it. The FDA approved drugs for alzheimer's belong to the category of acetylcholinesterase inhibitors. But most of the drugs have been observed to be associated with adverse side effects. In this study, we have developed a pharmacophore (responsible for interaction with acetylcholinesterase active site) based on the already existing drugs and drug candidates. This pharmacophore was used to search for novel AChE inhibitors with altogether different chemical scaffold using high throughput virtual screening and docking studies. Finally, we have reported two compounds, OPA and OMT, which possess high affinity for catalytic site of AChE enzyme and thus, can be considered as potential AChE inhibitors for the symptomatic treatment of Alzheimer's.
authors.affiliation: Department of Biotechnology, Delhi Technological University, Shahbad Daultpur, Bawana Road, Delhi 110042, India.
authors.forename: Jaspreet Kaur
authors.initials: JK
authors.lastname: Dhanjal
authors.affiliation: Department of Biotechnology, Delhi Technological University, Shahbad Daultpur, Bawana Road, Delhi 110042, India.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Sharma
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Campus, New Delhi 110067, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
authors.affiliation: Department of Biotechnology, Delhi Technological University, Shahbad Daultpur, Bawana Road, Delhi 110042, India. Electronic address: asmita1710@gmail.com.
authors.forename: Asmita
authors.initials: A
authors.lastname: Das
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000596:Amino Acids / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D062126:Databases, Chemical; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D062105:Molecular Docking Simulation; D014584:User-Computer Interface
chemical_list: D000596:Amino Acids; D002800:Cholinesterase Inhibitors; D008024:Ligands
keywords: Acetylcholinesterase inhibitors; Alzheimer's; Drug design; Molecular docking; Pharmacophore