| Title : New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease - Jalili-Baleh_2017_Eur.J.Med.Chem_139_280 |
| Author(s) : Jalili-Baleh L , Nadri H , Moradi A , Bukhari SNA , Shakibaie M , Jafari M , Golshani M , Homayouni Moghadam F , Firoozpour L , Asadipour A , Emami S , Khoobi M , Foroumadi A |
| Ref : Eur Journal of Medicinal Chemistry , 139 :280 , 2017 |
| Abstract : A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 7l with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 7l had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells. This compound could also inhibit AChE-induced and self-induced Abeta peptide aggregation. The advantages including synthetic accessibility, high potency and selectivity, low toxicity, adjunctive neuroprotective and Abeta aggregation inhibitory activity, make this compound as a new multifunctional lead for Alzheimer's disease drug discovery. |
| ESTHER : Jalili-Baleh_2017_Eur.J.Med.Chem_139_280 |
| PubMedSearch : Jalili-Baleh_2017_Eur.J.Med.Chem_139_280 |
| PubMedID: 28803044 |
Jalili-Baleh L, Nadri H, Moradi A, Bukhari SNA, Shakibaie M, Jafari M, Golshani M, Homayouni Moghadam F, Firoozpour L, Asadipour A, Emami S, Khoobi M, Foroumadi A (2017)
New racemic annulated pyrazolo[1,2-b]phthalazines as tacrine-like AChE inhibitors with potential use in Alzheimer's disease
Eur Journal of Medicinal Chemistry
139 :280
Jalili-Baleh L, Nadri H, Moradi A, Bukhari SNA, Shakibaie M, Jafari M, Golshani M, Homayouni Moghadam F, Firoozpour L, Asadipour A, Emami S, Khoobi M, Foroumadi A (2017)
Eur Journal of Medicinal Chemistry
139 :280