Síntese de derivados β-Cetoindois e avaliação da inibição da Acetilcolinesterase

Abstract

Alzheimer's disease (AD) affects the population of developed and developing countries and impacts the lives of patients. Considered the most common form of dementia, affecting mainly the elderly population. The disease has several hypotheses that seek to explain its causes based on several factors, such as cholinergic, amyloid cascade, Tau hyperphosphorylation and oxidative stress. Drugs that are capable of inhibiting the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are available. The use of antioxidants is also considered a promising strategy to avoid free radical damage, which can be used to prevent and treat AD. The objective of this study was to synthesize β-ketoindois derivatives and to evaluate the inhibition of the enzyme acetylcholinesterase and antioxidant activity. For the synthesis of derivatives β- ketoindois it was necessary to perform the optimization of the method. The anticholinesterase and butyrylcholinesterase activity was evaluated in vitro by puncture inhibition tests with the use of high performance liquid chromatography coupled to mass spectrometer (HPLC-MS). Indole derivatives synthesized (3a-3l) showed the ability to inhibit of electrophorus electricus enzyme (AChEee) and human butyrylcholinesterase enzyme (BChEhu), and seven of the compounds (3e,3g-3l) inhibited the human acetylcholinesterase enzyme (AChEhu). In addition, the antioxidant potential of the compounds (3a-3l) were evaluated by ultraviolet/visible (UV/Vis) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy and differential pulse voltammetry (DPV) in consideration of the recent use of antioxidant compounds in the complementary treatment and prevention of neurodegenerative diseases. Β- ketoindole derivatives are promising to be used as future prototypes for the treatment of AD.