Introduction–AD, the most common form of dementia, has a multifactorial etiology, and the current therapy (AChEIs and memantine) is unable to interrupt its progress and fatal outcome. This is reflected in the research programs that are oriented toward the development of new therapeutics able to operate on multiple targets involved in the disease progression.
A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized
to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE
and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor
(IC50 = 0.153 ± 0.016 uM) while the carbamate 11 was the most potent inhibitor of hBChE
(IC50 = 0.828 ± 0.067 uM). A molecular docking study indicated that the carbamate 8 was able to bind
In order to obtain multi-functional molecules for Alzheimer's disease, a series of deferiprone derivatives has been synthesized and evaluated in vitro with the hypothesis that they can restore the cholinergic tone and attenuate the dyshomeostasis of the metals mainly involved in the pathology. These compounds were designed as dual binding site AChE inhibitors: they possess an arylalkylamine moiety connected via an alkyl chain to a 3-hydroxy-4-pyridone fragment, to allow the simultaneous interaction with catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme.
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