Quinones bearing non-steroidal anti-inflammatory fragments as multitarget ligands for Alzheimer鈥檚 disease

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• 作者：Federica Prati ; Manuela Bartolini ; Elena Simoni ; Angela De Simone ; Antonella Pinto ; Vincenza Andrisano ; Maria Laura Bolognesi
• 关键词：Memoquin ; Alzheimer&rsquo ; s disease ; Non-steroidal anti-inflammatory drugs ; Amyloid aggregation inhibitors ; Acetylcholinesterase inhibitors
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：1 December, 2013
• 年：2013
• 卷：23
• 期：23
• 页码：6254-6258
• 全文大小：1169 K

文摘

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 A尾 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鈥檚 disease.