| Title : Discovery of new multifunctional selective acetylcholinesterase inhibitors: structure-based virtual screening and biological evaluation - Jiang_2019_J.Comput.Aided.Mol.Des_33_521 |
| Author(s) : Jiang CS , Ge YX , Cheng ZQ , Song JL , Wang YY , Zhu K , Zhang H |
| Ref : J Comput Aided Mol Des , 33 :521 , 2019 |
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Abstract :
Although the mechanism of Alzheimer's disease (AD) is still not fully understood, the development of multifunctional AChE inhibitors remains a research focus for AD treatment. In this study, 48 AChE candidate inhibitors were picked out from SPECS database through a pharmacophore- and molecular docking-based virtual screening. The biological evaluation results indicated that four compounds 7, 29, 41 and 48 with different scaffolds exhibited potent and selective AChE inhibitory activity, with the best IC50 value of 1.62 +/- 0.11 muM obtained for 48. Then their mechanism of action, the inhibition on Abeta aggregation, neurotoxicity, and neuroprotective activity against Abeta-induced nerve cell injury were well studied. The binding mode of 48 with AChE was also proposed. The present bioassay results indicated that these multifunctional AChE inhibitors were worth for further structural derivatization to make them the anti-AD lead compounds. |
| PubMedSearch : Jiang_2019_J.Comput.Aided.Mol.Des_33_521 |
| PubMedID: 30989573 |
Jiang CS, Ge YX, Cheng ZQ, Song JL, Wang YY, Zhu K, Zhang H (2019)
Discovery of new multifunctional selective acetylcholinesterase inhibitors: structure-based virtual screening and biological evaluation
J Comput Aided Mol Des
33 :521
Jiang CS, Ge YX, Cheng ZQ, Song JL, Wang YY, Zhu K, Zhang H (2019)
J Comput Aided Mol Des
33 :521