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 anti-acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme (BACE)1 activities compared to the reference, and is also able to inhibit Abeta 42 self-aggregation, Abeta 42 oligomer-binding to cell membrane and subsequently reactive oxygen species formation in both neuronal and microglial cells. The ability of AP2469 to interfere with Abeta 42 oligomer-binding to neuron and microglial cell membrane gives this molecule both neuroprotective and anti-inflammatory properties. These findings, together with its strong chain-breaking antioxidant performance, make AP2469 a potential drug able to modify the course of the disease.
        
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Tarozzi A, Bartolini M, Piazzi L, Valgimigli L, Amorati R, Bolondi C, Djemil A, Mancini F, Andrisano V, Rampa A (2014) From the dual function lead AP2238 to AP2469, a multi-target-directed ligand for the treatment of Alzheimer's disease Pharmacol Res Perspect2: e00023
Tarozzi A, Bartolini M, Piazzi L, Valgimigli L, Amorati R, Bolondi C, Djemil A, Mancini F, Andrisano V, Rampa A (2014) Pharmacol Res Perspect2: e00023