| Title : Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents - Luo_2019_Bioorg.Med.Chem__115190 |
| Author(s) : Luo W , Lv JW , Wang T , Zhang ZY , Guo HY , Song ZY , Wang CJ , Ma J , Chen YP |
| Ref : Bioorganic & Medicinal Chemistry , :115190 , 2019 |
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Abstract :
A novel series of graveolinine derivatives were synthesized and evaluated as potential anti-Alzheimer agents. Compound 5f exhibited the best inhibitory activity for acetylcholinesterase (AChE) and had surprisingly potent inhibitory activity for butyrylcholinesterase (BuChE), with IC50 values of 0.72muM and 0.16muM, respectively. The results from Lineweaver-Burk plot and molecular modeling study indicated non-competitive inhibition of AChE by compound 5f. In addition, these derivatives showed potent self-induced beta-amyloid (Abeta) aggregation inhibition. Moreover, 5f didn't show obvious toxicity against PC12 and HepG2 cells at 50muM. Finally, in vivo studies confirmed that 5f significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, these graveolinine derivatives should be thoroughly and systematically studied for the treatment of Alzheimer's disease. |
| PubMedSearch : Luo_2019_Bioorg.Med.Chem__115190 |
| PubMedID: 31744779 |
Luo W, Lv JW, Wang T, Zhang ZY, Guo HY, Song ZY, Wang CJ, Ma J, Chen YP (2019)
Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents
Bioorganic & Medicinal Chemistry
:115190
Luo W, Lv JW, Wang T, Zhang ZY, Guo HY, Song ZY, Wang CJ, Ma J, Chen YP (2019)
Bioorganic & Medicinal Chemistry
:115190