Title : Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities - Zang_2021_Molecules_26_ |
Author(s) : Zang Y , Liu K , Wang W , Li C , Ma J , Yang J , Chen X , Wang X , Zhang D |
Ref : Molecules , 26 : , 2021 |
Abstract :
The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC(50)) 1.63-4.62 microM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation. |
PubMedSearch : Zang_2021_Molecules_26_ |
PubMedID: 33671020 |
Zang Y, Liu K, Wang W, Li C, Ma J, Yang J, Chen X, Wang X, Zhang D (2021)
Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities
Molecules
26 :
Zang Y, Liu K, Wang W, Li C, Ma J, Yang J, Chen X, Wang X, Zhang D (2021)
Molecules
26 :