Flavone and chalcone derivatives as promising AChE and BuChE inhibitors for Alzheimer's disease treatment

NATALIA COLETTIS ; JOSEFINA HIGGS; CRISTINA WASOWSKI; DAMIJAN KNEZ; STANISLAV GOBEC; MARIEL MARDER

Mar del Plata

Congreso; XXX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2015

SAN

Alzheimer's disease (AD) is an age related neurodegenerative disorder associated with neuropathological and neurobehavioral changes accompanied by memory and cognitive impairments. The development of drugs with therapeutic potential in AD is one of the major targets in neuroscience. It has been shown that AChE activity is reduced in patients in the late phase of AD, whereas expression and concentration of butyrylcholinesterase (BChE) is compensatory and is increased. Inhibitors of acetylcholinesterase (AChE), such as galantamine, rivastigmine and donepezil, are prescribed to patients in the early stages of AD. The inhibitory effects of flavonoids on both AChE and BuChE have attracted great interest among researchers. We studied the effect of a wide range of natural and novel flavone and chalcone derivatives on murine AChE and both human and murine BuChE. Different grade of inhibition was observed depending on the compound and the enzyme tested.The most promising results were obtained for 3,3-dibromoflavanone (100 µM) that showed 100 % AChE inhibition. Flavone; chrysin; 6-methylflavone; 6-methoxy-3'-bromoflavone; 6,3'-dimethylflavone; 3'-methylflavone; 3-bromoflavone; 6-hydroxy-3´-bromoflavone and 3,3-dibromoflavanone (100 µM) showed > 75 % BuChE inhibition.Meanwhile the chalcone derivatives tested showed < 75 % inhibition on both enzymes. The effectiveness of some of the most active compounds will be evaluated in mice in behavioral tests that assess learning and memory.