Alzheimer's is a neurodegenerative
disease that causes dementia, or loss of brain function. It affects the parts
of the brain that deal with memory, thought, and language.
http://fr.wikipedia.org/wiki/Maladie_d'Alzheimer
It is well known that several factors are involved in the Alzheimer’s
disease (AD) (as well as beta-amyloid plaques, deposits in senile plaques and
tau-protein aggregation, oxidative stress and low levels of acetylcholine are
thought to play significant roles). Recently, monoamine oxidase B (MAO-B)
inhibitors have been proposed for the treatment of AD.
There is no medical treatment currently available to cure or to stop the
progression of Alzheimer's disease. For this reason, the urgent needs of new
therapeutic strategies in order to find more efficient and effective drugs for
AD are increased in the last years.
Our research interest involves the design, synthesis and pharmacological evaluation of new Multipotent
Anti-Alzheimer Drugs with dual inhibitory activity (AChE/MAO) and the capacity
to bind simultaneously at both CAS and PAS of AChE. Moreover, these prodrugs
is designed to cross the blood–brain barrier (BBB).
Molecular modelling studies have been
performed to check the real potential of these familie of compounds.
A docking
analysis has been performed comparing the predicted enzyme-bound conformation
of compound family.
In this way, the known orientation of donepezil fragments benzylpiperidin and
indanone were used to predict the binding conformation of I with AChE.
The Docking resul show that targeting of both catalytic and
peripheral sites of AChE will mainly depend on the length of the linker (-CH2-O-).
Alzheimer's is a neurodegenerative
disease that causes dementia, or loss of brain function. It affects the parts
of the brain that deal with memory, thought, and language. |
| http://fr.wikipedia.org/wiki/Maladie_d'Alzheimer |
There is no medical treatment currently available to cure or to stop the
progression of Alzheimer's disease. For this reason, the urgent needs of new
therapeutic strategies in order to find more efficient and effective drugs for
AD are increased in the last years.
Our research interest involves the design, synthesis and pharmacological evaluation of new Multipotent
Anti-Alzheimer Drugs with dual inhibitory activity (AChE/MAO) and the capacity
to bind simultaneously at both CAS and PAS of AChE. Moreover, these prodrugs
is designed to cross the blood–brain barrier (BBB).
In this regard, we have developed a multitarget molecule, ASS234, which according to the results of in vitro studies conducted, inhibits the aggregation of the ß-amyloid protein, involved in Alzheimer’s disease. At the same time, ASS234 stimulates cholinergic and monoaminergic transmission, key factors involved in cognitive function. In addition, ASS234 is able to cross the blood-brain barrier with an elevated multipotent profile designed on the basis of donepezil (Aricept®), one of the few e
ffective drugs in palliative and symptomatic treatments of the disease. In the development of this new molecule, researchers used the strategy of “multipotent drugs,” capable of acting simultaneously on different targets in the brain involved in this neurodegenerative disease, given that the paradigm used in the design of drugs based on the strategy of “one drug, one target” has shown to be unsuitable in offering satisfactory results.
Molecular modelling studies have been
performed to check the real potential of these familie of compounds.
A docking
analysis has been performed comparing the predicted enzyme-bound conformation
of compound family.
In this way, the known orientation of donepezil fragments benzylpiperidin and
indanone were used to predict the binding conformation of I with AChE.
The Docking resul show that targeting of both catalytic and
peripheral sites of AChE will mainly depend on the length of the linker (-CH2-O-).
