| Title : New classes of carbazoles as potential multi-functional anti-Alzheimer's agents - Choubdar_2019_Bioorg.Chem_91_103164 |
| Author(s) : Choubdar N , Golshani M , Jalili-Baleh L , Nadri H , Kucukkilinc TT , Ayazgok B , Moradi A , Moghadam FH , Abdolahi Z , Ameri A , Salehian F , Foroumadi A , Khoobi M |
| Ref : Bioorg Chem , 91 :103164 , 2019 |
| Abstract : Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase inhibitors. The synthesized compounds showed IC50 values of 0.11-36.5microM and 0.02-98.6microM against acetyl- and butyrylcholinesterase (AChE and BuChE), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 3s could bind effectively to the peripheral anionic binding site (PAS) and anionic site of the enzyme with mixed-type inhibition. Compound 3s was the most potent compound against AChE and BuChE and showed acceptable inhibition potency for self- and AChE-induced Abeta1-42 aggregation. Moreover, compound 3s could significantly protect PC12 cells against H2O2-induced toxicity. The results suggested that the compounds 3s could be considered as a promising multi-functional agent for further drug discovery development against Alzheimer's disease. |
| ESTHER : Choubdar_2019_Bioorg.Chem_91_103164 |
| PubMedSearch : Choubdar_2019_Bioorg.Chem_91_103164 |
| PubMedID: 31398601 |
Choubdar N, Golshani M, Jalili-Baleh L, Nadri H, Kucukkilinc TT, Ayazgok B, Moradi A, Moghadam FH, Abdolahi Z, Ameri A, Salehian F, Foroumadi A, Khoobi M (2019)
New classes of carbazoles as potential multi-functional anti-Alzheimer's agents
Bioorg Chem
91 :103164
Choubdar N, Golshani M, Jalili-Baleh L, Nadri H, Kucukkilinc TT, Ayazgok B, Moradi A, Moghadam FH, Abdolahi Z, Ameri A, Salehian F, Foroumadi A, Khoobi M (2019)
Bioorg Chem
91 :103164