Anti-Alzheimer’s Disease Activity of Bromophenols from a Red Alga, <i>Symphyocladia latiuscula</i> (Harvey) Yamada

Abstract

<i>Symphyocladia latiuscula</i> (Harvey) Yamada is a red alga with a myriad of bromophenols accompanied by a diverse array of biological activities. The main purpose of the present study was to characterize the anti-Alzheimer's disease activity of bromophenols from <i>S. latiuscula</i> via inhibition of cholinesterases (AChE and BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3β (GSK-3β). The results of enzyme inhibition assays demonstrated 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (<b>1</b>), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (<b>2</b>), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (<b>3</b>) as potent inhibitors of aforementioned enzymes. Among the tested bromophenols, <b>3</b> showed multifold higher inhibition of all of the tested enzymes. Enzyme kinetics revealed different modes of inhibition, and in silico molecular docking simulation demonstrated the importance of the 7-OH group and bromine number for H-bond and halogen-bond interactions, respectively. Similarly, <b>1</b>-<b>3</b> at 20 μM concentration showed more than 50% inhibition of self-induced Aβ_25-35 aggregation. These results suggest that bromophenols from <i>S. latiuscula</i>, especially highly brominated (<b>3</b>), may represent a novel class of anti-Alzheimer's disease drugs.