%0 Journal Article
%T Inhibitory Evaluation of Sulfonamide Chalcones on ¦Â-Secretase and Acylcholinesterase
%A Jae Eun Kang
%A Jung Keun Cho
%A Marcus J. Curtis-Long
%A Hyung Won Ryu
%A Jin Hyo Kim
%A Hye Jin Kim
%A Heung Joo Yuk
%A Dae Wook Kim
%A Ki Hun Park
%J Molecules
%D 2013
%I MDPI AG
%R 10.3390/molecules18010140
%X The action of ¦Â-secretase (BACE1) is strongly correlated with the onset of Alzheimer¡¯s disease (AD). Aminochalcone derivatives were examined for their ability to inhibit BACE1. Parent aminochalcones showed two digit micromolar IC 50s against BACE1. Potency was enhanced 10-fold or more by introducing benzenesulfonyl derivatives to the amino group: 1 (IC 50 = 48.2 ¦ÌM) versus 4a (IC 50 = 1.44 ¦ÌM) and 2 (IC 50 = 17.7 ¦ÌM) versus 5a (IC 50 = 0.21 ¦ÌM). The activity was significantly influenced by position and number of hydroxyl groups on the chalcone B-ring: 3,4-dihydroxy 5a (IC 50 = 0.21 ¦ÌM) > 4-hydroxy 4a (IC 50 = 1.44 ¦ÌM) > 2,4-dihydroxy 6 (IC 50 = 3.60 ¦ÌM) > 2,5-dihydroxy 7 (IC 50 = 16.87 ¦ÌM) > des hydroxy 4b (IC 50 = 168.7 ¦ÌM). Lineweaver-Burk and Dixon plots and their secondary replots indicate that compound 5a was a mixed inhibitor with reversible and time-dependent behavior. Potent BACE1 inhibitors 4a, c, f, 5a¨C c showed moderate inhibition against two other enzymes implicated in AD pathogenesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC 50s ranging between 56.1 ~ 95.8 ¦ÌM and 19.5 ~ 79.0 ¦ÌM, respectively.
%K sulfonamide chalcone
%K Alzheimer¡¯s disease (AD)
%K ¦Â-secretase
%K acetylcholinesterase (AChE)
%K butyrylcholinesterase (BChE)
%K mixed inhibition
%U http://www.mdpi.com/1420-3049/18/1/140