N- Alkyl carbazole derivatives as new tools for alzheimer's disease: Preliminary studies

Carmela Saturnino, Domenico Iacopetta, Maria Stefania Sinicropi, Camillo Rosano, Anna Caruso, Angelamaria Caporale, Nancy Marra, Barbara Marengo, Maria Adelaide Pronzato, Ortensia Ilaria Parisi, Pasquale Longo, Roberta Ricciarelli

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of "dementia", because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid β-peptide (Aβ) which leads to senile plaques formation and intracellular neurofibrillary tangles. Many studies have focused on the design and therapeutic use of new molecules able to inhibit Aβ aggregation. In this context, we evaluated the ability of two recently synthesized series of N- Alkyl carbazole derivatives to increase the Aβ soluble forms, through molecular docking simulations and in vitro experiments. Our data evidenced that two carbazole derivatives, the most active, adopt distinct binding modes involving key residues for Aβ fibrillization. They exhibit a good interfering activity on Aβ aggregation in mouse (N2a) cells, stably expressing wild- Type human amyloid precursor protein (APP) 695. These preliminary results are promising and we are confident that the N- Alkyl carbazole derivatives may encourage next future studies needed for enlarging the knowledge about the AD disease approach.

Original languageEnglish
Pages (from-to)9307-9317
Number of pages11
JournalMolecules
Volume19
Issue number7
DOIs
Publication statusPublished - 2014

Keywords

  • Alzheimer's disease
  • Amyloid β-peptide
  • N- Alkyl carbazole derivatives

ASJC Scopus subject areas

  • Organic Chemistry
  • Medicine(all)

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