title: N-alkyl carbazole derivatives as new tools for Alzheimer's disease: preliminary studies.
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.
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, Fisciano 84084 (SA), Italy. saturnino@unisa.it.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende 87036 (CS), Italy. domenico.iacopetta@unical.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Iacopetta
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende 87036 (CS), Italy. s.sinicropi@unical.it.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
authors.affiliation: Biopolymers and Proteomics IRCCS AOU San Martino-IST National Institute for Cancer Research Largo Benzi 10, Genova 16132, Italy. camillo.rosano@gmail.com.
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende 87036 (CS), Italy. anna.caruso@unical.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, Fisciano 84084 (SA), Italy. acaporale@unisa.it.
authors.forename: Angelamaria
authors.initials: A
authors.lastname: Caporale
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, Fisciano 84084 (SA), Italy. nancyma@hotmail.it.
authors.forename: Nancy
authors.initials: N
authors.lastname: Marra
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genova, via L.B. Alberti 2, Genova 16132, Italy. barbara.marengo@unige.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Marengo
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genova, via L.B. Alberti 2, Genova 16132, Italy. maidep@unige.it.
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Pronzato
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende 87036 (CS), Italy. ortensiailaria.parisi@unical.it.
authors.forename: Ortensia Ilaria
authors.initials: OI
authors.lastname: Parisi
authors.affiliation: Department of Sciences, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy. plongo@unisa.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Longo
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genova, via L.B. Alberti 2, Genova 16132, Italy. ricciarelli@medicina.unige.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D017077:Culture Media, Conditioned; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000517:prevention & control; D055550:Protein Stability; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D002227:Carbazoles; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)