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

Molecules

Carmela Saturnino⁵  Domenico Iacopetta¹  Maria Stefania Sinicropi¹  Camillo Rosano³  Anna Caruso¹  Angelamaria Caporale⁵  Nancy Marra⁵  Barbara Marengo⁴  Maria Adelaide Pronzato⁴  Ortensia Ilaria Parisi¹  Pasquale Longo² 

[1] Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende 87036 (CS), Italy; E-Mails:;Department of Sciences, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy;Biopolymers and Proteomics IRCCS AOU San Martino-IST National Institute for Cancer Research Largo Benzi 10, Genova 16132, Italy; E-Mail:;Department of Experimental Medicine, Section of General Pathology, University of Genova, via L.B. Alberti 2, Genova 16132, Italy; E-Mails:;Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, Fisciano 84084 (SA), Italy; E-Mails:

关键词: N-alkyl carbazole derivatives;    Alzheimer’s disease;    amyloid β-peptide;   

DOI  :  10.3390/molecules19079307

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.