alexa Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity.
Psychiatry

Psychiatry

Journal of Addiction Research & Therapy

Author(s): Bolognesi ML, Bartolini M, Tarozzi A, Morroni F, Lizzi F,

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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. Copyright © 2010 Elsevier Ltd. All rights reserved. This article was published in Bioorg Med Chem Lett and referenced in Journal of Addiction Research & Therapy

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