ACS Chemical Neuroscience,
Journal Year:
2024,
Volume and Issue:
15(15), P. 2756 - 2778
Published: July 30, 2024
Alzheimer's
disease
(AD)
is
the
most
prevalent
cause
of
dementia
and
characterized
by
low
levels
acetyl
butyrylcholine,
increased
oxidative
stress,
inflammation,
accumulation
metals,
aggregations
Aβ
tau
proteins.
Current
treatments
for
AD
provide
only
symptomatic
relief
without
impacting
pathological
hallmarks
disease.
In
our
ongoing
efforts
to
develop
naturally
inspired
novel
multitarget
molecules
AD,
through
extensive
medicinal
chemistry
efforts,
we
have
developed
13a,
harboring
key
functional
groups
not
but
also
targeting
able
chelate
iron,
inhibiting
NLRP3,
Aβ1–42
aggregation
in
various
models.
13a
exhibited
promising
anticholinesterase
activity
against
AChE
(IC50
=
0.59
±
0.19
μM)
BChE
5.02
0.14
with
excellent
antioxidant
properties
DPPH
assay
5.88
0.21
over
ferulic
acid
(56.49
0.62
μM).
The
molecular
docking
dynamic
simulations
further
corroborated
enzyme
inhibition
studies
confirmed
stability
these
complexes.
Importantly,
PAMPA-BBB
assay,
turned
out
be
a
molecule
that
can
efficiently
cross
blood–brain
barrier.
Notably,
iron-chelating
properties.
Furthermore,
effectively
inhibited
self-
metal-induced
aggregation.
It
worth
mentioning
demonstrated
no
symptom
cytotoxicity
up
30
μM
concentration
PC-12
cells.
Additionally,
NLRP3
inflammasome
mitigated
mitochondrial-induced
reactive
oxygen
species
mitochondrial
membrane
potential
damage
triggered
LPS
ATP
HMC-3
could
reduce
cellular
(ROS)
Drosophila
model
AD.
Finally,
was
found
efficacious
reversing
memory
impairment
scopolamine-induced
mouse
vivo
studies.
ex
assessments,
notably
modulates
superoxide,
catalase,
malondialdehyde
along
BChE.
These
findings
revealed
holds
promise
as
candidate
development
management.
ChemistrySelect,
Journal Year:
2025,
Volume and Issue:
10(16)
Published: April 1, 2025
Abstract
Alzheimer's
disease
(AD)
is
a
prevalent
indication
of
dementia
syndrome.
The
syndrome
commonly
manifests
as
AD.
2019
World
Report
estimates
that
there
are
over
50
million
people
worldwide
who
have
dementia,
and
number
projected
to
increase
150
by
2050.
AchE
(Acetylcholinesterase)
BchE
(butyrylcholinesterase)
enzymes
responsible
for
AD,
resulting
in
thinking
difficulties,
memory
loss,
dementia.
Researchers
looking
at
non‐toxic,
bioactive
ChE
inhibitors
found
nature.
Donepezil
galantamine,
example,
exclusively
target
AchE,
while
rivastigmine
tacrine
block
both.
development
potential
anti‐Alzheimer
molecules
has
gained
considerable
attention
recent
years.
Keeping
mind,
this
review
enables
the
synthesis
many
hybrid
analogs
containing
sulfur,
oxygen,
nitrogen
heterocyclic
moiety
barriers
AChE
BuChE
structure
activity
relationship
(SAR).
This
addresses
current
advancements
study
emphasizing
straightforward,
sustainable
synthetic
methods
synthesizing
anti‐AD
their
structure‐activity
relation
Preclinical
early
clinical
phases
highlighted,
research
on
generating
powerful
incredibly
effective
cholinesterase
altering
existing
treat
ACS Chemical Neuroscience,
Journal Year:
2021,
Volume and Issue:
13(1), P. 27 - 42
Published: Dec. 21, 2021
The
pathological
hallmarks
of
Alzheimer's
disease
(AD)
are
manifested
as
an
increase
in
the
level
oxidative
stress
and
aggregation
amyloid-β
protein.
In
vitro,
vivo,
silico
experiments
were
designed
carried
out
with
multifunctional
cholinergic
inhibitor,
F24
(EJMC-7a)
to
explore
its
neuroprotective
effects
AD
models.
neuroprotection
ability
was
tested
SH-SY5Y
cells,
a
widely
used
neuronal
cell
line.
pretreatment
subsequent
co-treatment
cells
different
doses
effective
rescuing
from
H2O2
induced
neurotoxicity.
treated
found
be
reduction
cellular
reactive
oxygen
species,
DNA
damage,
Aβ1–42
neurotoxicity,
which
validated
effectiveness.
exhibited
efficacy
vivo
Drosophila
model
by
eye
phenotypes
degeneration
caused
Aβ
toxicity.
Further,
computational
studies
monitor
interaction
between
aggregates.
corroborated
our
vitro
suggesting
modulation
F24.
brain
entry
studied
parallel
artificial
membrane
permeability
assay.
Finally,
at
1
2.5
mg/kg
Morris
water
maze
model.
properties
shown
strongly
suggest
that
features
this
molecule
provide
symptomatic
relief
act
disease-modifying
agent
treatment
AD.
results
indicated
natural
template-based
could
serve
lead
for
further
investigation
therapeutic
agents
management.
