International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(8), P. 3781 - 3781
Published: April 17, 2025
Acetylcholinesterase
(AChE)
is
a
critical
enzyme
involved
in
neurotransmission
by
hydrolyzing
acetylcholine
at
the
synaptic
cleft,
making
it
key
target
for
drug
discovery,
particularly
treatment
of
neurodegenerative
disorders
such
as
Alzheimer’s
disease.
Computational
approaches,
molecular
docking
and
dynamics
(MD)
simulations,
have
become
indispensable
tools
identifying
optimizing
AChE
inhibitors
predicting
ligand-binding
affinities,
interaction
mechanisms,
conformational
dynamics.
This
review
serves
comprehensive
guide
future
research
on
using
MD
simulations.
It
compiles
analyzes
studies
conducted
over
past
five
years,
providing
evaluation
most
widely
used
computational
tools,
including
AutoDock,
AutoDock
Vina,
GROMACS,
which
significantly
contributed
to
advancement
inhibitor
screening.
Furthermore,
we
identify
PDB
ID:
4EY7,
frequently
crystal
structure
studies,
highlight
Donepezil,
well-established
reference
molecule
employed
control
screening
novel
inhibitors.
By
examining
these
aspects,
this
aims
enhance
accuracy
reliability
virtual
approaches
researchers
selecting
appropriate
methodologies.
The
integration
simulations
not
only
improves
hit
identification
lead
optimization
but
also
provides
deeper
mechanistic
insights
into
AChE–ligand
interactions,
contributing
rational
design
more
effective
Archiv der Pharmazie,
Journal Year:
2022,
Volume and Issue:
356(4)
Published: Dec. 27, 2022
New
Schiff
base-bearing
thiosemicarbazones
(1-13)
were
obtained
from
4-hydroxy-3,5-dimethoxy
benzaldehyde
and
various
isocyanates.
The
structures
of
the
synthesized
molecules
elucidated
in
detail.
Density
functional
theory
calculations
also
performed
to
determine
spectroscopic
properties
compounds.
Moreover,
enzyme
inhibition
activities
these
compounds
investigated.
They
showed
highly
potent
effects
on
acetylcholinesterase
(AChE)
human
carbonic
anhydrases
(hCAs)
(KI
values
are
range
51.11
±
6.01
278.10
40.55
nM,
60.32
9.78
300.00
77.41
64.21
9.99
307.70
61.35
nM
for
AChE,
hCA
I,
II,
respectively).
In
addition,
molecular
docking
studies
performed,
confirmed
by
binding
affinities
most
derivatives.
Drug Development Research,
Journal Year:
2023,
Volume and Issue:
84(2), P. 275 - 295
Published: Jan. 4, 2023
Abstract
Aldose
reductase
(AR)
is
a
crucial
enzyme
of
the
polyol
pathway
through
which
glucose
metabolized
under
conditions
hyperglycemia
related
to
diabetes.
A
series
novel
acetic
acid
derivatives
containing
quinazolin‐4(3
H
)‐one
ring
(
1–22
)
was
synthesized
and
tested
for
in
vitro
AR
inhibitory
effect.
All
target
compounds
exhibited
nanomolar
activity
against
enzyme,
all
displayed
higher
as
compared
reference
drug
epalrestat.
Among
them,
Compound
19
,
named
2‐(4‐[(2‐[(4‐methylpiperazin‐1‐yl)methyl]‐4‐oxoquinazolin‐3(4
)‐ylimino)methyl]phenoxy)acetic
acid,
strongest
effect
with
K
I
value
61.20
±
10.18
nM.
Additionally,
these
were
investigated
L929,
nontumoral
fibroblast
cells,
MCF‐7,
breast
cancer
cells
using
MTT
assay.
Compounds
16
showed
lower
toxicity
normal
L929
cells.
The
compounds’
absorption,
distribution,
metabolism,
excretion
properties
also
evaluated.
Molecular
docking
simulations
used
look
into
possible
binding
mechanisms
inhibitors
AR.
Molecules,
Journal Year:
2024,
Volume and Issue:
29(2), P. 480 - 480
Published: Jan. 18, 2024
The
Lamiaceae
family
are
utilized
as
ornamental,
medicinal,
and
food
supplements
throughout
the
world.
current
study
focuses
on
a
comparative
analysis
of
phenolic
compositions
bioactivities
(including
antioxidant,
anticholinergic,
antibacterial
activities)
ethanolic
extracts
derived
from
aerial
parts
two
species
(Lavandula
stoechas
L.
Thymus
sipyleus
Boiss).
presence
compounds
phytochemicals
in
plant
was
identified
using
LC-MS/MS
technique.
revealed
that
vanillic
acid
(125,596.66
µg/L)
most
abundant
phytochemical
stoechas.
Kaempferol
(8550.52
substance
sipyleus.
assessment
antioxidant
efficacy
conducted
DPPH
(2.2-diphenyl-1-picryl-hydrazyl-hydrate),
ABTS
(2.2′-azino-bis
(3-ethylbenzothiazoline-6-sulfonic
acid)),
Fe3+–Fe2+
reducing,
CUPRAC
(Cu2+–Cu+
reducing)
assays.
anticholinergic
activity
samples
determined
acetylcholinesterase
(AChE)
inhibition
assay.
results
were
higher
T.
than
ethanol
extracts.
exhibited
radical
scavenging
ranging
15
to
18%,
while
had
effects
34%
38%.
AChE
potential
for
IC50
values
0.221
±
0.01
mg/mL
0.067
0.02
mg/mL,
respectively.
these
against
pathogenic
bacteria
isolates
MIC
(minimal
inhibitory
concentration)
method.
These
findings
indicated
possess
be
natural
antioxidants
realm
preservation.
Additionally,
their
antimicrobial
properties
suggest
therapeutic
utility
management
certain
diseases.
Saudi Pharmaceutical Journal,
Journal Year:
2024,
Volume and Issue:
32(2), P. 101959 - 101959
Published: Jan. 21, 2024
In
Indonesia,
there
are
many
types
of
citrus
where
parts
the
fruit,
leaves,
and
peel
can
be
utilized
as
food,
drinks,
spices,
medicine.
This
research
aims
to
determine
phytochemical
characteristics,
antioxidant
activities,
anti-inflammatory
activity
through
inhibition
NF-κB
sEH,
main
phytoconstituents
three
fruits
that
commonly
used
herbs
in
Indonesia.
The
flesh
