Novel Deoxyvasicinone-Donepezil Hybrids as Potential Multitarget Drug Candidates for Alzheimer's Disease.
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 Aβ1-42 aggregation. In particular, the hybrids 10a, 10d, 11a, and 11j exhibited excellent inhibitory activities against hAChE (IC50 = 56.14, 5.91, 3.29, and 8.65 nM, respectively), BACE1 (IC50 = 0.834, 0.167, 0.129, and 0.085 μM, respectively), and Aβ1-42 aggregation (IC50 = 13.26, 19.43, 9.26, and 5.41 μM, respectively). In addition, 10a and 11a exhibited very low cytotoxicity and showed remarkable neuroprotective activity against Aβ1-42-induced damage in SH-SY5Y cells.
['Du|Hongtao|H|0000-0002-6428-2401', 'Liu|Xinlian|X|', 'Xie|Jusen|J|', 'Ma|Fang|F|']
D000544:Alzheimer Disease D053829:Amyloid Precursor Protein Secretases D016282:Aspartic Acid Endopeptidases D002460:Cell Line D002800:Cholinesterase Inhibitors D000077265:Donepezil D004359:Drug Therapy, Combination D006801:Humans D066298:In Vitro Techniques D018697:Nootropic Agents D011799:Quinazolines
Alzheimer’s disease acetylcholinesterase deoxyvasicinone β-amyloid peptide β-secretase