Quinones bearing non-steroidal anti-inflammatory fragments as multitarget ligands for Alzheimer's disease.

Abstract

The anti-amyloid properties shared by several quinones inspired the design of a new series of hybrids derived from the multi-target drug candidate memoquin (1). The hybrids consist of a central benzoquinone core and a fragment taken from non-steroidal anti-inflammatory drugs, connected through polyamine linkers. The new hybrids retain the potent anti-aggregating activity of the parent 1, while exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)-6 were Aβ aggregation inhibitors even more potent than 1. The balanced amyloid/cholinesterase inhibitory profile is an added value that makes the present series of compounds promising leads against Alzheimer's disease.

• Authors: Federica Prati, Manuela Bartolini, Elena Simoni, Angela De Simone, Antonella Pinto, Vincenza Andrisano, Maria Laura Bolognesi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 23 Pg. 6254-8 (Dec 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 24140444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid
• Anti-Inflammatory Agents, Non-Steroidal
• Cholinesterase Inhibitors
• Ligands
• Quinones

Topics

• Alzheimer Disease (drug therapy)
• Amyloid (antagonists & inhibitors, metabolism)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, pharmacokinetics, pharmacology)
• Cholinesterase Inhibitors (chemistry, pharmacokinetics, pharmacology)
• Humans
• Ligands
• Mice
• Models, Molecular
• Protein Binding
• Quinones (chemistry, pharmacokinetics, pharmacology)
• Structure-Activity Relationship