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Fernández-Bachiller, María Isabel; Pérez, Concepción; González-Muñoz, Gema C; Conde, Santiago; López, Manuela G; Villarroya, Mercedes; García, Antonio G; Rodríguez-Franco, María Isabel
Journal of medicinal chemistry, 07/2010, Letnik: 53, Številka: 13Journal Article
Tacrine and PBT2 (an 8-hydroxyquinoline derivative) are well-known drugs that inhibit cholinesterases and decrease β-amyloid (Aβ) levels by complexation of redox-active metals, respectively. In this work, novel tacrine−8-hydroxyquinoline hybrids have been designed, synthesized, and evaluated as potential multifunctional drugs for the treatment of Alzheimer’s disease. At nano- and subnanomolar concentrations they inhibit human acetyl- and butyrylcholinesterase (AChE and BuChE), being more potent than tacrine. They also displace propidium iodide from the peripheral anionic site of AChE and thus could be able to inhibit Aβ aggregation promoted by AChE. They show better antioxidant properties than Trolox, the aromatic portion of vitamin E responsible for radical capture, and display neuroprotective properties against mitochondrial free radicals. In addition, they selectively complex Cu(II), show low cell toxicity, and could be able to penetrate the CNS, according to an in vitro blood−brain barrier model.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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