TY - JOUR
T1 - N- Alkyl carbazole derivatives as new tools for alzheimer's disease
T2 - Preliminary studies
AU - Saturnino, Carmela
AU - Iacopetta, Domenico
AU - Sinicropi, Maria Stefania
AU - Rosano, Camillo
AU - Caruso, Anna
AU - Caporale, Angelamaria
AU - Marra, Nancy
AU - Marengo, Barbara
AU - Pronzato, Maria Adelaide
AU - Parisi, Ortensia Ilaria
AU - Longo, Pasquale
AU - Ricciarelli, Roberta
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid β-peptide
KW - N- Alkyl carbazole derivatives
UR - http://www.scopus.com/inward/record.url?scp=84904822482&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904822482&partnerID=8YFLogxK
U2 - 10.3390/molecules19079307
DO - 10.3390/molecules19079307
M3 - Article
C2 - 24991761
AN - SCOPUS:84904822482
VL - 19
SP - 9307
EP - 9317
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 7
ER -