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.
L.Piazzi, A. Cavalli, F. Colizzi, F. Belluti, M. Bartolini, F. Mancini, et al. (2008). Multi-target-directed coumarin derivatives: hAChE and BAC1 inhibitors as potential anti-Alzheimer compounds. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 18, 423-426 [10.1016/j.bmcl.2007.09.100].
Multi-target-directed coumarin derivatives: hAChE and BAC1 inhibitors as potential anti-Alzheimer compounds
PIAZZI, LORNA;CAVALLI, ANDREA;COLIZZI, FRANCESCO;BELLUTI, FEDERICA;BARTOLINI, MANUELA;MANCINI, FRANCESCA;RECANATINI, MAURIZIO;ANDRISANO, VINCENZA;RAMPA, ANGELA
2008
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
