%0 Journal Article
%A Chioua, Mourad
%A Pérez Peña, Javier
%A García Font, Nuria
%A Moraleda, Ignacio
%A Iriepa, Isabel
%A Soriano, Elena
%A Marco Contelles, José
%A Oset Gasque, María Jesús
%T Pyranopyrazolotacrines as nonneurotoxic, Aβ-anti-aggregating and neuroprotective agents for Alzheimer’s disease
%D 2015
%@ 1756-8919
%U https://hdl.handle.net/20.500.14352/34805
%X Aim: Due to the complex nature of Alzheimer’s disease, there is a renewed search for multipotent, nonhepatotoxic tacrines. Results: This paper describes the synthesis and in vitro biological evaluation of eight new racemic 3-methyl-4-aryl-2,4,6,7,8,9-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolin-5-amines (pyranopyrazolotacrines, PPT) as nonhepatotoxic multipotent tacrine analogs. Among these compounds, PPT4 is the less hepatotoxic in the cell viability assay on HepG2 cells, showing a good neuroprotective effect in the decreased cortical neuron viability induced by oligomycin A/rotenone analysis. PPT4 is a selective and good, noncompetitive EeAChE inhibitor, able to completely inhibit the Aβ1–40 aggregation induced by acetylcholinesterase. Conclusion: A new family of permeable tacrine analogs, have been discovered for the potential treatment of Alzheimer’s disease.
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