Memoquin (1) is a lead compound multitargeted against Alzheimer's disease (AD). It is an AChE inhibitor, free-radical scavenger, and inhibitor of amyloid-β (Aβ) aggregation. A new series of 1 derivatives was designed and synthesized by linking its 2,5-diamino-benzoquinone core with motifs that are present in the structure of known amyloid binding agents like curcumin, the benzofuran derivative SKF64346, or the benzothiazole bearing compounds KHG21834 and BTA-1. The weaker AChE inhibitory potencies and the concomitant nearly equipotent anti-amyloid activities of the new compounds with respect to 1 resulted in a more balanced biological profile against both targets. Selected compounds turned out to be effective Aβ aggregation inhibitors in a cell-based assay. By properly combining two or more distinct pharmacological properties in a molecule, we can achieve greater effectiveness compared to single-targeted drugs for investigating AD

Multitargeted drugs discovery: Balancing anti-amyloid and anticholinesterase capacity in a single chemical entity

BOLOGNESI, MARIA LAURA;BARTOLINI, MANUELA;TAROZZI, ANDREA;MORRONI, FABIANA;LIZZI, FEDERICA;MILELLI, ANDREA;MINARINI, ANNA;ROSINI, MICHELA;HRELIA, PATRIZIA;ANDRISANO, VINCENZA;MELCHIORRE, CARLO
2011

Abstract

Memoquin (1) is a lead compound multitargeted against Alzheimer's disease (AD). It is an AChE inhibitor, free-radical scavenger, and inhibitor of amyloid-β (Aβ) aggregation. A new series of 1 derivatives was designed and synthesized by linking its 2,5-diamino-benzoquinone core with motifs that are present in the structure of known amyloid binding agents like curcumin, the benzofuran derivative SKF64346, or the benzothiazole bearing compounds KHG21834 and BTA-1. The weaker AChE inhibitory potencies and the concomitant nearly equipotent anti-amyloid activities of the new compounds with respect to 1 resulted in a more balanced biological profile against both targets. Selected compounds turned out to be effective Aβ aggregation inhibitors in a cell-based assay. By properly combining two or more distinct pharmacological properties in a molecule, we can achieve greater effectiveness compared to single-targeted drugs for investigating AD
Bolognesi M.L.; Bartolini M. ; Tarozzi A.; Morroni F. ; Lizzi F. ; Milelli A. ; Minarini A. ; Rosini M.; Hrelia P.; Andrisano V.; Melchiorre C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/108615
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