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- W2884605655 abstract "We report the synthesis and pharmacological evaluation of new 3-aminomethylindoles derivatives with neuroprotective properties designed to present multi-target activity centered on reducing the neuronal Ca2+ overload and preventing phosphatase 2A (PP2A) inhibition, which are two important early physiophathological events observed in neurodegenerative scenarios. Chemical syntheses of proposed compounds were achieved in two straightforward reaction steps with high yields. Most of the compounds mitigated the okadaic acid-provoked inhibition of PP2A and protected SH-SY5Y cells against toxic stimuli related to Tau-hyperphosphorylation and oxidative stress, similarly to the observed in Alzheimer's disease (AD). In addition, some of them mitigated the Ca2+ overload induced by depolarization. The derivative 1-(1-benzyl-5-chloro-1H-indol-3-yl)-N,N-dimethylmethanamine (19) outstood by its high recovery of the PP2A activity and blockade of voltage-gated Ca2+ channels, accompanied by good neuroprotective profile. These findings make this compound eligible for further preclinical assays with the goal of positioning new innovative drugs for the treatment of AD." @default.
- W2884605655 created "2018-08-03" @default.
- W2884605655 creator A5020190176 @default.
- W2884605655 creator A5034280470 @default.
- W2884605655 creator A5057643181 @default.
- W2884605655 creator A5066329127 @default.
- W2884605655 creator A5080800757 @default.
- W2884605655 creator A5087348082 @default.
- W2884605655 date "2018-09-01" @default.
- W2884605655 modified "2023-10-18" @default.
- W2884605655 title "Design and synthesis of multipotent 3-aminomethylindoles and 7-azaindoles with enhanced protein phosphatase 2A-activating profile and neuroprotection" @default.
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