Leng_2016_Chem.Biol.Drug.Des_88_889

Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of alpha, beta-unsaturated carbonyl-based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid beta-induced cytotoxicity was also studied. Six compounds including 3f, 3o, 3u, 3ae, 3af, and 3ag were discovered to be most protective against Abeta-induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO-B, AChE, and self-induced Abeta1-42 aggregation. The compound 3f exhibited best AChE (IC50 = 0.045 +/- 0.02 mum) inhibitory potential in addition to potent inhibition of MAO-B (IC50 = 0.88 +/- 0.12 mum). Furthermore, compound 3f disassembled the Abeta fibrils produced by self-induced Abeta aggregation by 78.2 +/- 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.