Universidad Complutense de Madrid
E-Prints Complutense

Pyranopyrazolotacrines as nonneurotoxic, Aβ-anti-aggregating and neuroprotective agents for Alzheimer’s disease

Impacto

Downloads

Downloads per month over past year

Chioua, Mourad and Pérez Peña, Javier and García Font, Nuria and Moraleda, Ignacio and Iriepa, Isabel and Soriano, Elena and Marco Contelles, José and Oset Gasque, María Jesús (2015) Pyranopyrazolotacrines as nonneurotoxic, Aβ-anti-aggregating and neuroprotective agents for Alzheimer’s disease. Future medicinal chemistry, 7 (7). pp. 845-855. ISSN 1756-8919

[img] PDF
Restringido a Repository staff only

2MB

Official URL: http://dx. doi.org/10.4155/FMC.15.35




Abstract

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.


Item Type:Article
Uncontrolled Keywords:Tacrine, Butyrylcholinesterase, ADMET, Molecular modeling
Subjects:Medical sciences > Pharmacy > Biochemistry
ID Code:32482
Deposited On:29 Jul 2015 07:46
Last Modified:04 Aug 2015 07:55

Origin of downloads

Repository Staff Only: item control page