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Molecules 2014, 19(7), 9307-9317;

N-Alkyl Carbazole Derivatives as New Tools for Alzheimer’s Disease: Preliminary Studies

Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, Fisciano 84084 (SA), Italy
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende 87036 (CS), Italy
Biopolymers and Proteomics IRCCS AOU San Martino-IST National Institute for Cancer Research Largo Benzi 10, Genova 16132, Italy
Department of Computer Engineering, Modeling, Electronics and Systems, University of Calabria, Rende 87036 (CS), Italy
Department of Experimental Medicine, Section of General Pathology, University of Genova, via L.B. Alberti 2, Genova 16132, Italy
Department of Sciences, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 8 May 2014 / Revised: 12 June 2014 / Accepted: 24 June 2014 / Published: 2 July 2014
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [555 KB, uploaded 2 July 2014]   |  


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. View Full-Text
Keywords: N-alkyl carbazole derivatives; Alzheimer’s disease; amyloid β-peptide N-alkyl carbazole derivatives; Alzheimer’s disease; amyloid β-peptide

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Saturnino, C.; Iacopetta, D.; Sinicropi, M.S.; Rosano, C.; Caruso, A.; Caporale, A.; Marra, N.; Marengo, B.; Pronzato, M.A.; Parisi, O.I.; Longo, P.; Ricciarelli, R. N-Alkyl Carbazole Derivatives as New Tools for Alzheimer’s Disease: Preliminary Studies. Molecules 2014, 19, 9307-9317.

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