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

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

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Alzheimer?s disease (AD) is an age related neurodegenerative disorderassociated with neuropathological and neurobehavioral changesaccompanied by memory and cognitive impairments. The developmentofdrugs with therapeutic potential in AD is one of the majortargets inneuroscience.It has been shown that AChE activity is reduced in patients inthelate phase of AD, whereas expression and concentration ofbutyrylcholinesterase (BChE) is compensatory and is increased.Inhibitors of acetylcholinesterase (AChE), such as galantamine,rivastigmine and donepezil, are prescribed to patients in theearlystages of AD. The inhibitory effects of flavonoids on both AChEandBuChE have attracted great interest among researchers.We studied the effect of a wide range of natural and novelflavone andchalcone derivatives on murine AChE and both human and murineBuChE.Different grade of inhibition was observed depending on thecompoundand the enzyme tested.The most promising results were obtained for3,3-dibromoflavanone (100µM) that showed 100% AChE inhibition. Flavone; chrysin;6-methylflavone;6-methoxy-3?-bromoflavone; 6,3?-dimethylflavone;3?-methylflavone; 3-bromoflavone; 6-hydroxy-3´-bromoflavone and3,3-dibromoflavanone (100 µM) showed >75 % BuChE inhibition.Meanwhile the chalcone derivatives tested showed