| Title : Discovery, biological evaluation and molecular dynamic simulations of butyrylcholinesterase inhibitors through structure-based pharmacophore virtual screening - Lu_2021_Future.Med.Chem_13_769 |
| Author(s) : Lu T , Liu Y , Chen H , Han C , Feng X , Zhou H , Li Y |
| Ref : Future Med Chem , 13 :769 , 2021 |
|
Abstract :
Aim: Butyrylcholinesterase (BChE) is a crucial therapeutic target because it is associated with multiple pathological elements of Alzheimer's disease (AD). An integrated computational strategy was employed to exploit effective BChE inhibitors. Methods & results: Ten compounds derived from the Enamine database by structure-based pharmacophore virtual screening were further evaluated for biological activity; out of the ten, only five had an IC(50) of less than 100 microM. Among these five compounds, a new molecule, 970180, presented the most potency against BChE, with an IC(50) of 4.24 +/- 0.16 microM, and acted as a mixed-type inhibitor. Molecular dynamic simulations and absorption, distribution, metabolism and excretion prediction further confirmed its high potential as a good candidate of BChE inhibitor. Furthermore, cytotoxicity of molecule 970180 was not observed at concentrations up to 50 microM, and the molecule also showed a prominent neuroprotective effect compared with tacrine at 25 and 50 microM. Conclusion: This study provides an effective structure-based pharmacophore virtual screening method to discover BChE inhibitors and provide new choices for the development of BChE inhibitors, which may be beneficial for AD patients. |
| PubMedSearch : Lu_2021_Future.Med.Chem_13_769 |
| PubMedID: 33759552 |
Lu T, Liu Y, Chen H, Han C, Feng X, Zhou H, Li Y (2021)
Discovery, biological evaluation and molecular dynamic simulations of butyrylcholinesterase inhibitors through structure-based pharmacophore virtual screening
Future Med Chem
13 :769
Lu T, Liu Y, Chen H, Han C, Feng X, Zhou H, Li Y (2021)
Future Med Chem
13 :769