The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer’s disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains antiacetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Ab42 self aggregation, Ab42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Ab42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and antiinflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease

From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer’s disease

TAROZZI, ANDREA;BARTOLINI, MANUELA;VALGIMIGLI, LUCA;AMORATI, RICCARDO;BOLONDI, CECILIA;ANDRISANO, VINCENZA;RAMPA, ANGELA
2014

Abstract

The development of drugs with different pharmacological properties appears to be an innovative therapeutic approach for Alzheimer’s disease. In this article, we describe a simple structural modification of AP2238, a first dual function lead, in particular the introduction of the catechol moiety performed in order to search for multi-target ligands. The new compound AP2469 retains antiacetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Ab42 self aggregation, Ab42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Ab42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and antiinflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease
2014
Tarozzi A.; Bartolini M.; Piazzi L.; Valgimigli L.; Amorati R.; Bolondi C.; Djemil A.; Mancini F.; Andrisano V.; Rampa A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/400177
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