The
search
for
acetylcholinesterase
(AChE)
inhibitors
produced
by
natural
sources
is
of
great
significance
the
prevention
and
therapy
Alzheimer's
disease
has
been
widely
concerned.
In
this
study,
fisetin,
a
flavonoid
compound
plant
origin,
displayed
mixed
inhibition
mode
on
AChE
(IC50
=
8.88
±
0.14
μM).
Fluorescence
spectra
analysis
revealed
that
fisetin
statically
quenched
fluorescence,
ground
state
complex
was
formed
hydrogen
bonds
hydrophobic
interactions.
Circular
dichroism
assays
showed
induced
structure
loosened
with
decrease
in
α-helix
structure.
Computer
simulation
exhibited
bound
to
both
peripheral
anionic
site
(PAS)
catalytic
active
(CAS)
increased
stability
AChE.
Interestingly,
combination
galantamine
enhanced
binding
affinity
between
further
loosened,
while
still
type.
heatmap
indicated
(0.2
μM)
combined
(2.25
had
significant
synergy
inhibition,
probably
because
at
PAS-AChE
conformation
changes
gorge
CAS,
which
loose
mixture,
so
finally
interaction
substrate
strongly
affected.
This
work
may
offer
theoretical
reference
functional
research
as
potential
inhibitor
an
supplement
galantamine.
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
21(11)
Опубликована: Июль 24, 2024
Abstract
To
optimize
the
ultrasonic‐assisted
biphasic
aqueous
extraction
conditions
for
polyphenolic
compounds
from
Vaccinium
dunalianum
Wight
leaves
and
investigate
their
antioxidant
tyrosinase
inhibition
activities,
single‐factor
experiments
were
conducted
to
effects
of
ethanol
volume
fraction
(%),
ammonium
sulfate
mass
solid‐liquid
ratio
(g/mL),
ultrasonic
temperature
(°C),
time
(min)
on
content
during
extraction.
Based
these
experiments,
three
key
factors
influencing
selected
response
surface
methodology
(RSM)
optimization.
The
results
indicated
that
under
26
%
ethanol,
20
sulfate,
a
1
:
30,
35
minutes
at
50
°C,
polyphenol
reached
61.62
mg/g.
relative
contents
6′‐
O
‐caffeoylarbutin,
β
‐arbutin,
chlorogenic
acid
34.45
%,
4.56
31.06
respectively.
DPPH⋅
ABTS
+
⋅
scavenging
rates
above
95
96
respectively,
ferric
reducing
ability
exhibited
significant
dose‐effect
relationship.
monophenolase
diphenolase
activities
43.84
35.73
optimized
process
polyphenols
demonstrated
activities.
ONCOLOGIE,
Год журнала:
2024,
Номер
26(5), С. 813 - 829
Опубликована: Июль 31, 2024
Abstract
Objectives
Melanoma
remains
a
challenge
due
to
the
lack
of
effective
and
low-toxicity
treatments.
Litsea
cubeba
essential
oil
(LEO),
known
for
its
tyrosinase
inhibitory
activity,
has
shown
promise
as
an
anti-melanoma
compound,
although
robust
scientific
evidence
is
lacking.
Methods
We
conducted
GC-MS
analysis
identify
major
components
LEO
screened
were
further
evaluated
on
A375
HaCaT
cells
using
CCK-8
assay.
Network
pharmacology
was
employed
predict
potential
targets
PharmMapper
SwissTarget
Prediction
databases,
with
melanoma-related
sourced
from
GeneCards
database.
Protein–protein
interaction
(PPI)
network
created
STRING
Cytoscape.
Gene
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
pathway
enrichment
analyses
performed
through
DAVI
Additionally,
we
constructed
natural
product-main
components-core
targets-pathways-disease
(NMCPD)
in
Cytoscape
molecular
docking
PyMOL
Autodock
Vina.
Results
revealed
neral
(
cis
-citral)
geranial
trans
primary
active
LEO.
Cell
assays
demonstrated
that
citral
mixture,
combination
LEO,
effectively
inhibited
cell
growth
IC
50
values
35.94
±
1.23
μM
12.00
0.96
μg/mL,
while
exhibiting
minimal
toxicity
67.72
2.96
22.32
2.53
μg/mL.
Screening
identified10
hub
among
190
common
between
drug
disease-related
targets.
KEGG
suggested
therapeutic
effects
melanoma
by
modulating
signaling
pathways.
Molecular
strong
binding
affinity
RXRA
ESR1,
suggesting
citral,
principal
component,
regulates
multiple
pathways
therapy.
Conclusions
These
findings
support
utility
treatment
highlight
importance
exploring
inhibitors
development
novel
drugs.
Biochemistry,
Год журнала:
2024,
Номер
63(16), С. 2063 - 2074
Опубликована: Авг. 7, 2024
Melanin
biosynthesis
in
different
organisms
is
performed
by
a
tyrosinase
action.
Excessive
enzyme
activity
and
pigment
accumulation
result
diseases
disorders
including
skin
cancers,
blemishes,
darkening.
In
fruits
vegetables,
it
causes
unwanted
browning
of
these
products
reduces
their
appearance
quality
economic
value.
Inhibiting
finding
novel
powerful
safe
inhibitors
are
highly
important
agriculture,
food,
medical,
pharmaceutical
industries.
this
regard,
the
present
study,
some
synthetic
pyridine-based
compounds
2,6-bis
(tosyloxymethyl)
pyridine
(compound
3),
(butylthiomethyl)
4),
(phenylthiomethyl)
5)
were
synthesized
for
first
time,
inhibitory
potencies
assessed
on
mushroom
diphenolase
activity.
The
results
showed
that
while
all
tested
significantly
decreased
activity,
4
5
had
highest
effects
(respectively,
80
89%
inhibition
with
IC50
values
17.0
9.0
μmol
L–1),
mechanism
was
mixed-type
both
compounds.
Ligand-binding
studies
carried
out
fluorescence
quenching
molecular
docking
methods
to
investigate
enzyme–compound
interactions.
Fluorescence
revealed
can
form
nonfluorescent
complexes
its
intrinsic
emission
static
process.
Molecular
analyses
predicted
binding
positions
amino
acid
residues
involved
These
appear
be
suitable
candidates
more
inhibition.
The
search
for
acetylcholinesterase
(AChE)
inhibitors
produced
by
natural
sources
is
of
great
significance
the
prevention
and
therapy
Alzheimer's
disease
has
been
widely
concerned.
In
this
study,
fisetin,
a
flavonoid
compound
plant
origin,
displayed
mixed
inhibition
mode
on
AChE
(IC50
=
8.88
±
0.14
μM).
Fluorescence
spectra
analysis
revealed
that
fisetin
statically
quenched
fluorescence,
ground
state
complex
was
formed
hydrogen
bonds
hydrophobic
interactions.
Circular
dichroism
assays
showed
induced
structure
loosened
with
decrease
in
α-helix
structure.
Computer
simulation
exhibited
bound
to
both
peripheral
anionic
site
(PAS)
catalytic
active
(CAS)
increased
stability
AChE.
Interestingly,
combination
galantamine
enhanced
binding
affinity
between
further
loosened,
while
still
type.
heatmap
indicated
(0.2
μM)
combined
(2.25
had
significant
synergy
inhibition,
probably
because
at
PAS-AChE
conformation
changes
gorge
CAS,
which
loose
mixture,
so
finally
interaction
substrate
strongly
affected.
This
work
may
offer
theoretical
reference
functional
research
as
potential
inhibitor
an
supplement
galantamine.
