Sun_2022_Eur.J.Med.Chem_234_114210

Reference

Title : Development of 5-hydroxyl-1-azabenzanthrone derivatives as dual binding site and selective acetylcholinesterase inhibitors - Sun_2022_Eur.J.Med.Chem_234_114210
Author(s) : Sun X , Wang Y , Lei Z , Yue S , Chen L , Sun J
Ref : Eur Journal of Medicinal Chemistry , 234 :114210 , 2022
Abstract :

A series of novel 5-hydroxyl-1-azabenzanthrone derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of Alzheimer's disease (AD). The most effective Compound 16 showed selective inhibition of acetylcholinesterase (eeAChE IC(50) = 0.045 microM; eeBuChE IC(50) = 19.68 microM; SI = 437.33). Most of the compounds showed cytoprotective effects on PC12 cells damaged by hydrogen peroxide, which might be related to their antioxidant activity. Further experiments confirmed that 16 exhibited anti-apoptotic effects at low concentrations and reduced the relative level of ROS generation in PC12 cells. The expression level of proteins related to antioxidant stress pathway in PC12 cells was relatively increased after administrated with 16, which may be beneficial to delay the progression of the disease. Moreover, 16 was evaluated to be safe in vivo and in vitro, and showed good overall pharmacokinetic performance and high bioavailability (Foral = 55.5%). Besides, 16 showed comparable performance in ameliorating the scopolamine-induced cognition impairment to donepezil. In addition, in vitro BBB permeability experiments confirmed that 16 had high BBB permeability.

PubMedSearch : Sun_2022_Eur.J.Med.Chem_234_114210
PubMedID: 35303485

Related information

Citations formats

Sun X, Wang Y, Lei Z, Yue S, Chen L, Sun J (2022)
Development of 5-hydroxyl-1-azabenzanthrone derivatives as dual binding site and selective acetylcholinesterase inhibitors
Eur Journal of Medicinal Chemistry 234 :114210

Sun X, Wang Y, Lei Z, Yue S, Chen L, Sun J (2022)
Eur Journal of Medicinal Chemistry 234 :114210