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

COLETTIS N; HIGGS J; WASOWSKI C; KNEZ D; GOBEC S; MARDER M

Mar del Plata

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

Sociedad Argentina de Investigación en Neurociencias

Alzheimer?s disease (AD) is an age related neurodegenerative disorderassociated with neuropathological and neurobehavioral changesaccompanied by memory and cognitive impairments. The development ofdrugs with therapeutic potential in AD is one of the major targets inneuroscience.It has been shown that AChE activity is reduced in patients in thelate 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 the earlystages of AD. The inhibitory effects of flavonoids on both AChE andBuChE have attracted great interest among researchers.We studied the effect of a wide range of natural and novel flavone andchalcone derivatives on murine AChE and both human and murine BuChE.Different grade of inhibition was observed depending on the compoundand the enzyme tested.The most promising results were obtained for 3,3-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