Abstract
Coumarin is a naturally occurring bioactive pharmacophore with wide occurrence among central nervous system (CNS)-active small molecules. 8-Acetylcoumarin, one of the natural coumarins, is a mild inhibitor of cholinesterases and β-secretase, which are vital targets of Alzheimer's disease. Herein, we synthesized a series of coumarin-triazole hybrids as potential multitargeted drug ligands (MTDLs) with better activity profiles. The coumarin-triazole hybrids occupy the cholinesterase active site gorge from the peripheral to the catalytic anionic site. The most active analogue, 10b, belonging to the 8-acetylcoumarin core, inhibits acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase-1 (BACE-1) with IC50 values of 2.57, 3.26, and 10.65 μM, respectively. The hybrid, 10b, crosses the blood-brain barrier via passive diffusion and inhibits the self-aggregation of amyloid-β monomers. The molecular dynamic simulation study reveals the strong interaction of 10b with three enzymes and forming stable complexes. Overall, the results warrant a detailed preclinical investigation of the coumarin-triazole hybrids.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
