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 Abeta 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.
Prati F, Bartolini M, Simoni E, De Simone A, Pinto A, Andrisano V, Bolognesi ML (2013) Quinones bearing non-steroidal anti-inflammatory fragments as multitarget ligands for Alzheimer's disease Bioorganic & Medicinal Chemistry Lett23: 6254-8
Prati F, Bartolini M, Simoni E, De Simone A, Pinto A, Andrisano V, Bolognesi ML (2013) Bioorganic & Medicinal Chemistry Lett23: 6254-8
