| Title : Pd-Catalyzed Direct Diversification of Natural Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of N-Aryl Huperzine A Analogues - Miao_2021_J.Nat.Prod_84_2374 |
| Author(s) : Miao SX , Wan LX , He ZX , Zhou XL , Li X , Gao F |
| Ref : Journal of Natural Products , 84 :2374 , 2021 |
| Abstract : The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of N-(hetero)aryl analogues (1-32) of the natural anti-Alzheimer's disease drug huperzine A (HPA) was prepared via palladium-catalyzed Buchwald-Hartwig cross-coupling reactions of HPA with various aryl bromides in good yields. Most of the N-aryl-huperzine A (N-aryl-HPA) analogues showed good acetylcholinesterase (AChE) inhibitory activity in in vitro experiments. Three arylated huperzine A analogues (14, 19, and 30) exhibited stronger anti-AChE activity than HPA. The 5-methoxy-2-pyridyl analogue (30) displayed the most potent AChE inhibition activity, with an IC(50) value of 1.5 microM, which was 7.6-fold more active than HPA. Compound 30 also exhibited better neuroprotective activity for H(2)O(2)-induced damage in SH-SY5Y cells than HPA. Structure-activity relationship analysis suggested that the electron density of the installed aromatic ring or heteroaromatic ring played a significant role in inducing the AChE inhibition activity. Overall, compound 30 showed the advantages of easy synthesis, high potency and selectivity, and improved neuroprotection, making it a potential huperzine-type lead compound for Alzheimer's disease drug development. |
| ESTHER : Miao_2021_J.Nat.Prod_84_2374 |
| PubMedSearch : Miao_2021_J.Nat.Prod_84_2374 |
| PubMedID: 34445873 |
Miao SX, Wan LX, He ZX, Zhou XL, Li X, Gao F (2021)
Pd-Catalyzed Direct Diversification of Natural Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of N-Aryl Huperzine A Analogues
Journal of Natural Products
84 :2374
Miao SX, Wan LX, He ZX, Zhou XL, Li X, Gao F (2021)
Journal of Natural Products
84 :2374