| Title : Design, synthesis and evaluation of novel ferulic acid-O-alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease - Sang_2017_Eur.J.Med.Chem_130_379 |
| Author(s) : Sang Z , Pan W , Wang K , Ma Q , Yu L , Yang Y , Bai P , Leng C , Xu Q , Li X , Tan Z , Liu W |
| Ref : Eur Journal of Medicinal Chemistry , 130 :379 , 2017 |
| Abstract : A series of novel ferulic acid-O-alkylamines derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. In vitro studies displayed that all the synthesized target compounds showed impressive inhibitory activity against butyrylcholinesterase (BuChE), significant inhibition/disaggregation of self-induced beta-amyloid (Abeta) aggregation and acted as potential antioxidants. Particularly, compound 7f, one of the most potent BuChE inhibitor (IC50 value of 0.021 muM for equine serum BuChE, 8.63 muM for ratBuChE and 0.07 muM for human serum BuChE), was found to be a good acetylcholinesterase (AChE) inhibitor (IC50 = 2.13 muM for electric eel AChE, 1.8 muM for ratAChE and 3.82 muM for human erythrocytes AChE), and the result of molecular docking provided an explanation for its selective BuChE inhibitory activity. Compound 7f also had noteworthy inhibitory effects on self-induced Abeta1-42 aggregation (50.8 +/- 0.82%) and was found to disaggregate self-induced Abeta1-42 aggregation (38.7 +/- 0.65%), which was further elucidated by the transmission electron microscopy. Meanwhile, compound 7f showed the modest antioxidant activity (0.55 eq of Trolox), good protective effect against H2O2-induced PC12 cell injury, with low toxicity. Moreover, compound 7f could cross the blood-brain barrier (BBB) in vitro. Significantly, compound 7f did not exhibit any acute toxicity in mice at doses up to 1000 mg/kg, and the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Taken together, the results indicated that compound 7f is a very promising multifunctional agent in the treatment of Alzheimer's disease, particularly the advanced stages of AD. |
| ESTHER : Sang_2017_Eur.J.Med.Chem_130_379 |
| PubMedSearch : Sang_2017_Eur.J.Med.Chem_130_379 |
| PubMedID: 28279845 |
Sang Z, Pan W, Wang K, Ma Q, Yu L, Yang Y, Bai P, Leng C, Xu Q, Li X, Tan Z, Liu W (2017)
Design, synthesis and evaluation of novel ferulic acid-O-alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease
Eur Journal of Medicinal Chemistry
130 :379
Sang Z, Pan W, Wang K, Ma Q, Yu L, Yang Y, Bai P, Leng C, Xu Q, Li X, Tan Z, Liu W (2017)
Eur Journal of Medicinal Chemistry
130 :379