Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation

A novel series of deoxyvasicinone-tetrahydro-beta-carboline hybrids were synthesized and evaluated as acetylcholinesterase (AChE) and beta-amyloid peptide (A beta) aggregation inhibitors for the treatment of Alzheimer's disease. The results revealed that the derivatives had multifunctional profiles, including AChE inhibition, A beta(1-42) aggregation inhibition, and neuroprotective properties. Inspiringly, hybrids 8b and 8d displayed excellent inhibitory activities against hAChE (IC50 = 0.93 and 1.08 nM, respectively) and A beta(1-42) self-aggregation (IC50 = 19.71 and 2.05 mu M, respectively). In addition, 8b and 8d showed low cytotoxicity and good neuroprotective activity against A beta(1-42)-induced damage in SH-SY5Y cells.