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Closed Access item Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer’s disease
|Authors:||Marco Contelles, José Luis|
de los Ríos, Cristóbal
Luque, F. Javier
Rodríguez Franco, María Isabel
López, Manuela G.
García, Antonio G.
do Carmo Carreiras, María
|Publisher:||American Chemical Society|
|Citation:||Journal of Medicinal Chemistry 52 : 2724–2732 (2009)|
|Abstract:||Tacripyrines (1-14) have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist
such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines
are selective and potent AChE inhibitors in the nanomolar range. The mixed type inhibition of hAChE
activity of compound 11 (IC50 105 ( 15 nM) is associated to a 30.7 ( 8.6% inhibition of the proaggregating
action of AChE on the A and a moderate inhibition of A self-aggregation (34.9 ( 5.4%). Molecular
modeling indicates that binding of compound 11 to the AChE PAS mainly involves the (R)-11 enantiomer,
which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11.
Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the
blood-brain barrier, emerging as lead candidates for treating AD.|
|Publisher version (URL):||http://dx.doi.org/10.1021/jm801292b|
|Appears in Collections:||(IQM) Artículos|
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