Pharmaceuticals,
Journal Year:
2024,
Volume and Issue:
17(5), P. 639 - 639
Published: May 15, 2024
Neurodegenerative
disorders
(NDs)
include
a
range
of
chronic
conditions
characterized
by
progressive
neuronal
loss,
leading
to
cognitive,
motor,
and
behavioral
impairments.
Common
examples
Alzheimer's
disease
(AD)
Parkinson's
(PD).
The
global
prevalence
NDs
is
on
the
rise,
imposing
significant
economic
social
burdens.
Despite
extensive
research,
mechanisms
underlying
remain
incompletely
understood,
hampering
development
effective
treatments.
Excitotoxicity,
particularly
glutamate-mediated
excitotoxicity,
key
pathological
process
implicated
in
NDs.
Targeting
N-methyl-D-aspartate
(NMDA)
receptor,
which
plays
central
role
holds
therapeutic
promise.
However,
challenges,
such
as
blood-brain
barrier
penetration
adverse
effects,
extrapyramidal
have
hindered
success
many
NMDA
receptor
antagonists
clinical
trials.
This
review
explores
molecular
antagonists,
emphasizing
their
structure,
function,
types,
future
prospects
treating
research
competitive
noncompetitive
quest
for
treatments
still
faces
hurdles.
partly
because
same
that
necessitates
blockage
under
also
responsible
normal
physiological
function
receptors.
Allosteric
modulation
receptors
presents
potential
alternative,
with
GluN2B
subunit
emerging
attractive
target
due
its
enrichment
presynaptic
extrasynaptic
receptors,
are
major
contributors
excitotoxic-induced
cell
death.
low
side-effect
profiles,
selective
like
ifenprodil
radiprodil
encountered
obstacles
poor
bioavailability
Moreover,
selectivity
these
often
relative,
they
been
shown
bind
other
GluN2
subunits,
albeit
minimally.
Recent
advancements
developing
phenanthroic
naphthoic
acid
derivatives
offer
promise
enhanced
GluN2B,
GluN2A
or
GluN2C/GluN2D
improved
pharmacodynamic
properties.
Additional
challenges
antagonist
conflicting
preclinical
results,
well
complexity
neurodegenerative
poorly
defined
subtypes.
Although
multifunctional
agents
targeting
multiple
degenerative
processes
being
explored,
data
limited.
Designing
antagonists/modulators
polycyclic
moieties
multitarget
properties
would
be
addressing
disorders.
understanding
structure
coupled
collaborative
efforts
drug
design,
imperative
realizing
antagonists/modulators.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
38(1)
Published: Jan. 23, 2023
A
series
of
novel
quinoline-O-carbamate
derivatives
was
rationally
designed
for
treating
Alzheimer's
disease
(AD)
by
multi-target-directed
ligands
(MTDLs)
strategy.
The
target
compounds
were
synthesised
and
evaluated
AChE/BuChE
inhibition
anti-inflammatory
property.
in
vitro
activities
showed
that
compound
3f
a
reversible
dual
eeAChE/eqBuChE
inhibitor
with
IC50
values
1.3
µM
0.81
µM,
respectively.
Moreover,
displayed
good
property
decreasing
the
production
IL-6,
IL-1β
NO.
In
addition,
presented
significant
neuroprotective
effect
on
Aβ25-35-induced
PC12
cell
injury.
Furthermore,
stabilities
artificial
gastrointestinal
fluids,
liver
microsomes
plasma.
could
improve
AlCl3-induced
zebrafish
AD
model
increasing
level
ACh.
Therefore,
promising
multifunctional
agent
treatment
AD.
Frontiers in Aging Neuroscience,
Journal Year:
2023,
Volume and Issue:
15
Published: March 3, 2023
With
the
development
trend
of
an
aging
society,
Alzheimer’s
disease
(AD)
has
become
urgent
problem
in
field
medicine
worldwide.
Cognitive
impairment
AD
patients
leads
to
a
decline
ability
perform
daily
living
and
abnormalities
behavior
personality,
causing
abnormal
psychiatric
symptoms,
which
seriously
affect
life
patients.
Currently,
mainly
drug
therapy
is
used
for
clinic,
but
large
proportion
will
experience
efficacy
not
working,
even
some
drugs
bring
severe
sleep
disorders.
Acupuncture,
with
its
unique
concept
treatment
method,
been
validated
through
number
experiments
proved
reliability
acupuncture
AD.
Many
advances
have
made
study
neurobiological
mechanisms
AD,
further
demonstrating
good
advantages
This
review
first
summarizes
pathogenesis
then
illustrates
research
progress
includes
effect
on
changes
biochemical
indicators
vivo
specific
mechanism
action
exert
therapeutic
effect.
Changes
relevant
similarly
validate
effectiveness
treatment.
The
clinical
mechanistic
studies
are
intensified
fit
need
social
development.
It
believed
that
achieve
new
achievements
as
progresses.
Chemical Physics Impact,
Journal Year:
2023,
Volume and Issue:
7, P. 100361 - 100361
Published: Nov. 14, 2023
A
series
of
32
molecules
derived
from
7-prenyloxy-2,3-dihydroflavanone
and
5-hydroxy-7-prenyloxy-2,3-dihydro-flavanone
possessing
an
inhibitory
activity
against
the
Acetylcholinesterase
(AChE)
enzyme
were
studied
using
structure-activity
(QSAR)
investigations.
Electronic
descriptors
calculated
Gaussian
software
DFT
method
at
B3YP/6-31G(d,
p)
level.
In
addition,
constitutional,
physicochemical,
topological
Chem3D
software.
The
best
model
obtained
by
multiple
linear
regression
(MLR)
was
subjected
to
external
internal
statistical
validations.
What
is
more,
applicability
domain
(ad)
has
been
defined
for
built
Williams
plot.
We
have
designed
new
molecular
structures
similar
basis
giving
dataset
their
predicted
model.
Then,
docking
used
predict
affinity
between
newly
inhibitors
candidates
AChE
protein.
This
study
completed
dynamic
simulation
(MDs)
stability
formed
complexes,
RMSD
RMSF
plots
complexes
analyzed.
