| Title : Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors - Wang_2017_Bioorg.Med.Chem_25_360 |
| Author(s) : Wang L , Wang Y , Tian Y , Shang J , Sun X , Chen H , Wang H , Tan W |
| Ref : Bioorganic & Medicinal Chemistry , 25 :360 , 2017 |
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Abstract :
A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- and submicromolar ranges. The most potent compound 3 exhibited comparable IC50 to the commercially available drug (rivastigmine). To better understand their structure activity relationships (SAR) and mechanisms of enzyme-inhibitor interactions, kinetic and molecular modeling studies including molecular docking and molecular dynamics (MD) simulations were carried out. Furthermore, compound 3 blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells and shows the required druggability and low cytotoxicity, suggesting this hybrid is a promising multifunctional drug candidate for Alzheimer's disease (AD) treatment. |
| PubMedSearch : Wang_2017_Bioorg.Med.Chem_25_360 |
| PubMedID: 27856236 |
Wang L, Wang Y, Tian Y, Shang J, Sun X, Chen H, Wang H, Tan W (2017)
Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors
Bioorganic & Medicinal Chemistry
25 :360
Wang L, Wang Y, Tian Y, Shang J, Sun X, Chen H, Wang H, Tan W (2017)
Bioorganic & Medicinal Chemistry
25 :360