1. Academic Validation
  2. Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity

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

  • Bioorg Med Chem Lett. 2011 May 1;21(9):2655-8. doi: 10.1016/j.bmcl.2010.12.093.
Maria Laura Bolognesi 1 Manuela Bartolini Andrea Tarozzi Fabiana Morroni Federica Lizzi Andrea Milelli Anna Minarini Michela Rosini Patrizia Hrelia Vincenza Andrisano Carlo Melchiorre
Affiliations

Affiliation

  • 1 Department of Pharmaceutical Sciences-Alma Mater Studiorum-Bologna University, Via Belmeloro 6, 40126 Bologna, Italy. marialaura.bolognesi@unibo.it
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.

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