Virtual screening, ADMET prediction, molecular docking, and dynamic simulation studies of natural products as BACE1 inhibitors for the management of Alzheimer’s disease
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Ноя. 2, 2024
Alzheimer's
disease
(AD)
is
a
degenerative
neurological
disorder
that
chronically
and
irreversibly
affects
memory,
cognitive
function,
learning
ability,
organizational
skills.
Numerous
studies
have
demonstrated
BACE1
as
critical
therapeutic
target
for
AD,
emphasizing
the
need
specific
inhibition
of
to
develop
effective
therapeutics.
However,
current
inhibitors
certain
limitations.
Therefore,
aim
this
study
was
identify
potential
novel
candidates
derived
from
natural
products
can
be
utilized
treatment
AD.
To
achieve
this,
80,617
compounds
ZINC
database
were
subjected
virtual
screening
subsequently
filtered
according
rule
five
(RO5),
leading
identification
1,200
compounds.
Subsequently,
underwent
molecular
docking
against
receptor,
utilizing
high-throughput
(HTVS),
standard
precision
(SP),
extra
(XP)
techniques
high-affinity
ligands.
Of
50
ligands
exhibited
highest
G-Scores
in
HTVS,
further
analysis
conducted
using
SP
scoring
methods.
This
led
seven
with
enhanced
binding
affinities,
which
then
additional
via
XP
scoring.
Finally,
stability
most
promising
ligand
relation
assessed
through
dynamics
(MD)
simulations.
The
computational
energy
values
enzymes
ranged
between
−
6.096
7.626
kcal/mol.
Among
these,
2
(L2)
best
at
-7.626
kcal/mol
BACE1.
MD
simulations
confirmed
BACE1-L2
complex,
formation
robust
interaction
L2
enzymes.
Additionally,
pharmacokinetic
drug-likeness
evaluations
indicated
non-carcinogenic
able
permeate
blood-brain
barrier
(BBB).
findings
will
contribute
narrowing
down
selection
subsequent
vitro
vivo
testing.
Язык: Английский
The Advancements of Marine Natural Products in the Treatment of Alzheimer’s Disease: A Study Based on Cell and Animal Experiments
Marine Drugs,
Год журнала:
2025,
Номер
23(3), С. 91 - 91
Опубликована: Фев. 20, 2025
As
life
expectancy
rises
and
the
aging
population
grows,
Alzheimer’s
disease
(AD)
has
become
a
significant
global
health
concern.
AD
is
complex
neurodegenerative
disorder
with
an
unclear
etiology.
Current
hypotheses
primarily
focus
on
β-amyloid
(Aβ)
aggregation,
tau
protein
hyperphosphorylation,
neuroinflammation
as
key
pathological
processes.
Given
limited
efficacy
of
existing
therapeutic
strategies,
there
urgent
need
to
explore
novel
treatment
options.
Marine
natural
products
have
garnered
attention
due
their
unique
chemical
structures
diverse
bioactivities,
demonstrating
potential
for
multi-target
interventions
in
AD.
This
review
systematically
summarizes
roles
marine-derived
compounds,
including
polysaccharides,
carotenoids,
polyphenols,
modulating
Aβ
mitigating
pathology,
regulating
gut–brain
axis
dysfunction.
Furthermore,
challenges
current
research
are
discussed,
emphasis
improving
blood–brain
barrier
permeability
optimizing
drug
delivery
systems
facilitate
clinical
translation.
Язык: Английский