Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds.
Lorna Piazzi, Andrea Cavalli, Francesco Colizzi, Federica Belluti, Manuela Bartolini, Francesca Mancini, Maurizio Recanatini, Vincenza Andrisano, Angela Rampa
Index: Bioorg. Med. Chem. Lett. 18(1) , 423-6, (2008)
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Abstract
The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD.