Indazole derivatives as selective inhibitors of butyrylcholinesterase with effective blood-brain-barrier permeability profile
Document Type
Article
Publication Date
1-1-2024
Abstract
Alzheimer's disease (AD) is a chronic disease that is multifactorial. Its underlying cause and mechanisms are yet to be fully understood and numerous research are underway to develop more effective drug candidates. This research explores the synthesis of an indazole-containing novel drug targeting AD, particularly by inhibiting cholinesterase activity. Among the 17 indazole derivatives synthesized in this study, compound 4q was demonstrated to have potent and selective butyrylcholinesterase (BChE) inhibitory activity. Molecular docking simulations revealed that the binding of 4q with BChE was through hydrophobic and polar interactions. It was also found to easily permeate through the blood-brain-barrier via an in vitro model and is non-toxic when tested against SH-SY5Y cells.
Keywords
Alzheimer's disease, Blood-brain-barrier, Cholinesterase, Enzyme inhibition, Indazoles
Divisions
nanotechnology
Funders
School of Science, Monash University Malaysia and Nanotechnology and Catalysis Research Centre, Universiti Malaya
Publication Title
Medicinal Chemistry Research
Volume
33
Issue
2
Publisher
Springer Verlag
Publisher Location
233 SPRING STREET, 6TH FLOOR, NEW YORK, NY 10013 USA