Title : Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT4 receptors activities for the treatment of Alzheimer's disease - Lalut_2020_Sci.Rep_10_3014 |
Author(s) : Lalut J , Payan H , Davis A , Lecoutey C , Legay R , Sopkova-de Oliveira Santos J , Claeysen S , Dallemagne P , Rochais C |
Ref : Sci Rep , 10 :3014 , 2020 |
Abstract :
A rigidification strategy was applied to the preclinical candidate donecopride, an acetylcholinesterase inhibitor possessing 5-HT4R agonist activity. Inspired by promising bioactive benzisoxazole compounds, we have conducted a pharmacomodulation study to generate a novel series of multitarget directed ligands. The chemical synthesis of the ligand was optimized and compounds were evaluated in vitro against each target and in cellulo. Structure-activity relationship was supported by docking analysis in human acetylcholinesterase binding site. Among the synthesized compounds, we have identified a novel hybrid 32a (3-[2-[1-(cyclohexylmethyl)-4-piperidyl]ethyl]-4-methoxy-1,2-benzoxazole) able to display nanomolar acetylcholinesterase inhibitory effects and nanomolar Ki for 5-HT4R. |
PubMedSearch : Lalut_2020_Sci.Rep_10_3014 |
PubMedID: 32080261 |
Lalut J, Payan H, Davis A, Lecoutey C, Legay R, Sopkova-de Oliveira Santos J, Claeysen S, Dallemagne P, Rochais C (2020)
Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT4 receptors activities for the treatment of Alzheimer's disease
Sci Rep
10 :3014
Lalut J, Payan H, Davis A, Lecoutey C, Legay R, Sopkova-de Oliveira Santos J, Claeysen S, Dallemagne P, Rochais C (2020)
Sci Rep
10 :3014