| Title : Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment - Czarnecka_2018_Eur.J.Med.Chem_145_760 |
| Author(s) : Czarnecka K , Chufarova N , Halczuk K , Maciejewska K , Girek M , Skibinski R , Jonczyk J , Bajda M , Kabzinski J , Majsterek I , Szymanski P |
| Ref : Eur Journal of Medicinal Chemistry , 145 :760 , 2018 |
| Abstract : A novel series of 9-amino-1,2,3,4-tetrahydroacridine and 5,6-dichloronicotinic acid moiety were conjugated with different linkers. Afterwards new derivatives were evaluated as potential multifunctional acetylcholinesterase inhibitors (AChEIs), anti-Alzheimer's disease (AD) drug candidates. All the compounds were synthesized and tested for capacity for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Specifically, the most promising derivative 3b (IC50=1.02nM) had higher inhibitory potency compared to the reference drug, tacrine. Consequently, kinetic studies of 3b compound showed a mixed-type inhibition of both AChE and BuChE. Afterwards the best potent AChE inhibitor has been examined on amyloid beta (Abeta) self-induced aggregation. Furthermore, 3b compound was tested in various concentrations and had moderate activity against Abeta aggregation. Inhibition of Abeta aggregation was 46.63% and 19.41% at 50muM and 5muM concentrations, respectively. Moreover, no cytotoxicity was observed for the mentioned concentrations. Therefore, 3b compound is a promising multipotent agent for the treatment of AD. |
| ESTHER : Czarnecka_2018_Eur.J.Med.Chem_145_760 |
| PubMedSearch : Czarnecka_2018_Eur.J.Med.Chem_145_760 |
| PubMedID: 29353726 |
Czarnecka K, Chufarova N, Halczuk K, Maciejewska K, Girek M, Skibinski R, Jonczyk J, Bajda M, Kabzinski J, Majsterek I, Szymanski P (2018)
Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment
Eur Journal of Medicinal Chemistry
145 :760
Czarnecka K, Chufarova N, Halczuk K, Maciejewska K, Girek M, Skibinski R, Jonczyk J, Bajda M, Kabzinski J, Majsterek I, Szymanski P (2018)
Eur Journal of Medicinal Chemistry
145 :760