Chioua, MouradPérez Peña, JavierGarcía Font, NuriaMoraleda, IgnacioIriepa, IsabelSoriano, ElenaMarco Contelles, JoséOset Gasque, María Jesús2023-06-192023-06-1920151756-891910.4155/FMC.15.35https://hdl.handle.net/20.500.14352/34805Aim: 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.engjournal articlehttp://dx. doi.org/10.4155/FMC.15.35http://www.future-science.com/loi/fmc/restricted access577.1TacrineButyrylcholinesteraseADMETMolecular modelingBioquímica (Farmacia)