Title : Phthalimide-(N-alkylbenzylamine) cysteamide hybrids as multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation - Zhang_2021_Chem.Biol.Drug.Des__ |
Author(s) : Zhang H , Song Q , Yu G , Cao Z , Qiang X , Liu X , Deng Y |
Ref : Chemical Biology Drug Des , : , 2021 |
Abstract :
The complex pathogenesis of Alzheimer's disease (AD) calls for multi-target approach for disease treatment. Herein, based on the MTDLs strategy, a series of phthalimide-(N-alkylbenzylamine) cysteamide hybrids were designed, synthesized and investigated in vitro for the purpose. Most of the target compounds were found to be potential multi-target agents. In vitro results showed that compound 9e was the representative compound in this series, endowed with high EeAChE and HuAChE inhibitory potency (IC(50) = 1.55microM and 2.23 microM, respectively), good inhibitory activity against self-induced Abeta(1-42) aggregation (36.08% at 25 microM) and moderate antioxidant capacity (ORAC-FL value was 0.68 Trolox equivalents). Molecular docking studies rationalized the binding mode of 9e in both PAS and CAS of AChE. Moreover, 9e displayed excellent ability to against H(2) O(2) -induced PC12 cell injury and penetrate BBB. Overall, these results highlighted that compound 9e was an effective and promising multi-target agent for further anti-AD drug development. |
PubMedSearch : Zhang_2021_Chem.Biol.Drug.Des__ |
PubMedID: 34143938 |
Zhang H, Song Q, Yu G, Cao Z, Qiang X, Liu X, Deng Y (2021)
Phthalimide-(N-alkylbenzylamine) cysteamide hybrids as multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation
Chemical Biology Drug Des
:
Zhang H, Song Q, Yu G, Cao Z, Qiang X, Liu X, Deng Y (2021)
Chemical Biology Drug Des
: