Luo_2011_J.Enzyme.Inhib.Med.Chem_26_706

A novel series of N,N'-bis-methylenedioxybenzyl-alkylenediamines 5a-5g have been designed, synthesized and evaluated as bivalent anti-Alzheimer's disease ligands. The enzyme inhibition assay results indicated that compounds 5e-5g inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the micromolar range (IC(50), 2.76-4.24 microM for AChE and 3.02-5.14 microM for BuChE), which was in the same potential as the reference compound rivastigmine (IC(50), 5.50 microM for AChE and 1.60 microM for BuChE). It was found that compounds could bind simultaneously to the peripheral and catalytic sites of AChE. beta-Amyloid (Abeta) aggregation inhibition assay results showed that compound 5e exhibited highest self-mediated Abeta fibril aggregation inhibition activity (40.3%) with a similar potential as curcumin (41.6%). It was also found that 5e-5g did not affect neuroblastoma cell viability at the concentration of 50 muM.