Du_2019_ACS.Chem.Neurosci_10_2397

In this study, we designed and synthesized a series of deoxyvasicinone-donepezil hybrids and determined whether they could be used as novel multitarget inhibitors for Alzheimer's disease. In vitro studies showed that most of the hybrids demonstrated moderate to potent inhibition of hAChE, BACE1, and Abeta(1-42) aggregation. In particular, the hybrids 10a, 10d, 11a, and 11j exhibited excellent inhibitory activities against hAChE (IC(50) = 56.14, 5.91, 3.29, and 8.65 nM, respectively), BACE1 (IC(50) = 0.834, 0.167, 0.129, and 0.085 microM, respectively), and Abeta(1-42) aggregation (IC(50) = 13.26, 19.43, 9.26, and 5.41 microM, respectively). In addition, 10a and 11a exhibited very low cytotoxicity and showed remarkable neuroprotective activity against Abeta(1-42)-induced damage in SH-SY5Y cells.