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Closed Access item Novel Tacrine – 8-Hydroxyquinoline Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Neuroprotective, Cholinergic, Antioxidant, and Copper-Complexing Properties
|Authors:||Fernández Bachiller, María Isabel|
González Muñoz, Gema C.
López, Manuela G.
García, Antonio G.
Rodríguez Franco, María Isabel
|Publisher:||American Chemical Society|
|Citation:||Journal of Medicinal Chemistry 53 : 4927–4937 (2010)|
|Abstract:||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
|Publisher version (URL):||http://dx.doi.org/10.1021/jm100329q|
|Appears in Collections:||(IQM) Artículos|
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