Symphyocladia
latiuscula
(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
S. latiuscula
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 (
1
), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (
2
), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (
3
) as potent inhibitors of aforementioned enzymes. Among the
tested bromophenols,
3
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,
1
–
3
at 20 μM concentration showed more than
50% inhibition of self-induced Aβ
25–35
aggregation.
These results suggest that bromophenols from
S. latiuscula
, especially highly brominated (
3
), may represent a
novel class of anti-Alzheimer’s disease drugs.