| Title : Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease: Synthesis, Pharmacological Evaluation, and Molecular Modeling of Amino-Alkyl-Substituted Fluoro-Chalcones Derivatives - Liu_2015_Chem.Biol.Drug.Des_86_517 |
| Author(s) : Liu HR , Zhou C , Fan HQ , Tang JJ , Liu LB , Gao XH , Wang QA , Liu WK |
| Ref : Chemical Biology Drug Des , 86 :517 , 2015 |
|
Abstract :
A new series of-fluoro chalcones-substituted amino-alkyl derivatives (3a 3l) were designed, synthesized, characterized and evaluated for the inhibitory activity against acetylcholinesterase and butyrylcholinesterase. The results showed that the alteration of fluorine atom position and amino-alkyl groups markedly influenced the activity and the selectivity of chalcone derivates in inhibiting acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses the most potent inhibitory against acetylcholinesterase (IC50 = 0.21 +/- 0.03 mumol/L), and the highest selectivity for acetylcholinesterase over butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and enzyme kinetic study on compound 3l supported its dual acetylcholinesterase inhibitory profile, simultaneously binding at the catalytic active and peripheral anionic site of the enzyme. |
| PubMedSearch : Liu_2015_Chem.Biol.Drug.Des_86_517 |
| PubMedID: 25588967 |
Liu HR, Zhou C, Fan HQ, Tang JJ, Liu LB, Gao XH, Wang QA, Liu WK (2015)
Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease: Synthesis, Pharmacological Evaluation, and Molecular Modeling of Amino-Alkyl-Substituted Fluoro-Chalcones Derivatives
Chemical Biology Drug Des
86 :517
Liu HR, Zhou C, Fan HQ, Tang JJ, Liu LB, Gao XH, Wang QA, Liu WK (2015)
Chemical Biology Drug Des
86 :517