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Elsevier, Bioorganic and Medicinal Chemistry Letters, 23(23), p. 6254-6258

DOI: 10.1016/j.bmcl.2013.09.091

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

This paper is available in a repository.
This paper is available in a repository.

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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.