Uncovering the Natural Inhibitors From Medicinal Plants to Alleviate Human Cancers Targeting the p53 Protein: An In Silico Approach
ChemistrySelect,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: Jan. 1, 2025
Abstract
The
tumor
suppressor
p53
protein
plays
a
key
role
in
controlling
several
essential
cellular
responses,
including
cell
growth,
development,
and
apoptosis,
helping
to
prevent
cancer
development.
In
various
cancers,
loss
of
function
results
prolonged
replication
inhibition
programmed
death.
There
are
few
options
available
target
p53,
but
they
come
with
limitations.
For
this
reason,
there
is
need
for
novel
drug
candidates
maintain
functionality.
Therefore,
our
study
aims
identify
potential
natural
bioactive
compounds
through
comprehensive
silico
methods
such
as
molecular
docking,
MM/GBSA
(molecular
mechanics
generalized
born
surface
area),
ADME/T
(absorption,
distribution,
metabolism,
excretion,
toxicity),
dynamics
(MD)
simulation
against
the
targeted
p53.
Initially,
462
phytochemicals
from
23
medicinal
plants
were
screened
using
docking
MM‐GBSA
studies
find
phytochemicals.
From
studies,
top
three
compounds,
CID‐3469,
CID‐5280372,
CID‐591524,
selected
based
on
their
good
binding
affinities
further
investigation,
where
all
showed
better
drug‐likeness
no
toxicity
analysis.
MD
depicted
structural
stability
phytocompounds
complexes
protein.
This
shows
insights
into
development
treatment.
Language: Английский
Comprehensive Metabolite Profiling and Evaluation of Anti-nociceptive and Anti-inflammatory Potencies of Nypa fruticans (Wurmb.) Leaves: Experimental and In-Silico Approaches.
Heliyon,
Journal Year:
2025,
Volume and Issue:
11(3), P. e42074 - e42074
Published: Jan. 21, 2025
Globally,
inflammation
and
pain
are
among
the
most
prevalent
health
issues.
The
use
of
medicinal
plants
to
alleviate
these
conditions
is
growing.
This
study
comprehensively
investigated
analgesic
anti-inflammatory
properties
ethyl-acetate
extract
Nypa
fruticans
(EENF)
leaves,
traditionally
used
in
folk
Medicine.
High-performance
liquid
chromatography
(HPLC)
gas
chromatography-mass
spectroscopy
(GC-MS)
were
employed
identify
phytochemicals
EENF.
In
vitro
antioxidant
studies
conducted
determine
antioxidative
Formalin-induced
paw
edema
assay
was
assess
in-vivo
activity
whereas;
acetic
acid-induced
writhing
test,
hot
plate
tail
immersion
test
performed
evaluate
vivo
anti-nociceptive
effects.
identified
compounds
subsequently
evaluated
by
computational
against
cyclooxygenase-2
enzyme.
EENF
demonstrated
significant
both
DPPH
scavenging
(IC50:
105.18
μg/mL)
reducing
power
(RC50:1752.76
μg/mL).
assay,
exhibited
highest
(50.39
%
67.72
%)
inhibition
at
fourth
hour
200
400
mg/kg
body
weight,
accordingly.
Moreover,
all
modulation
(p
<
0.001)
a
dose-dependent
manner.
Among,
23
phytocompounds,
promising
ones
determined
be
potential
agents
through
molecular
docking
ADME/T
analysis.
Molecular
dynamics
simulations
(MDS)
confirmed
stability
protein-ligand
complexes.
Two
phytochemicals,
(-)
Epicatechin
(CID
72276)
Quercetin
5280343),
outperformed
standard
drug,
diclofenac
sodium,
MDS
studies.
Both
experimental
in-silico
have
scientifically
verified
traditional
treating
inflammatory
disease.
Overall,
possess
excellent
as
natural
lead
for
COX-2
inhibition.
Further
research,
including
pure
compound
isolation
biomolecular
studies,
needed
understand
underlying
mechanisms
activities.
Language: Английский
Identification of acetylcholinesterase inhibitors from traditional medicinal plants for Alzheimer's disease using in silico and machine learning approaches
RSC Advances,
Journal Year:
2024,
Volume and Issue:
14(47), P. 34620 - 34636
Published: Jan. 1, 2024
Acetylcholinesterase
(AChE)
holds
significance
in
Alzheimer's
disease
(AD),
where
cognitive
impairment
correlates
with
insufficient
acetylcholine
levels.
AChE's
role
involves
the
breakdown
of
acetylcholine,
moderating
cholinergic
neuron
activity
to
prevent
overstimulation
and
signal
termination.
Hence,
inhibiting
AChE
emerges
as
a
potential
treatment
avenue
for
AD.
A
library
2500
compounds,
derived
from
25
traditionally
used
medicinal
plants,
was
constructed
using
IMPAAT
database
traditional
plants.
The
canonical
SMILES
these
compounds
were
collected
underwent
virtual
screening
based
on
physicochemical
properties,
subsequent
determination
IC
Language: Английский
Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer’s Disease Therapeutics
Biomedicines,
Journal Year:
2025,
Volume and Issue:
13(2), P. 279 - 279
Published: Jan. 23, 2025
Alzheimer’s
disease
(AD)
is
traditionally
viewed
through
the
lens
of
amyloid
cascade
hypothesis,
implicating
amyloid-beta
and
tau
protein
aggregates
as
main
pathological
culprits.
However,
burgeoning
research
points
to
brain’s
resident
immune
cells,
microglia,
critical
players
in
AD
pathogenesis,
progression,
potential
therapeutic
interventions.
This
review
examines
dynamic
roles
microglia
within
intricate
framework
AD.
We
detail
involvement
these
cells
neuroinflammation,
explaining
how
their
activation
response
fluctuations
may
influence
trajectory.
further
elucidate
complex
relationship
between
pathology.
study
highlights
dual
nature
which
contribute
both
aggregation
clearance
protein.
Moreover,
an
in-depth
analysis
interplay
unveils
significant,
yet
often
overlooked,
impact
this
interaction
on
neurodegeneration
Shifting
from
conventional
approaches,
we
assess
current
treatments
primarily
targeting
introduce
novel
strategies
that
involve
manipulating
microglial
functions.
These
innovative
methods
herald
a
paradigm
shift
management
Finally,
explore
field
precision
diagnosis
pursuit
robust
biomarkers.
underline
more
profound
comprehension
biology
could
enrich
essential
areas,
potentially
paving
way
for
accurate
diagnostic
tools
tailored
treatment
strategies.
In
conclusion,
expands
perspective
pathology
treatment,
drawing
attention
multifaceted
microglia.
As
continue
enhance
our
understanding
microglial-focused
interventions
emerge
promising
frontier
bolster
arsenal
fight
against
Language: Английский
A Comprehensive Evaluation of the Neuropharmacological Potential of Methanolic Leaf Extract of Acanthus ebracteatus (Vahl.) Using Experimental and In Silico Approaches
Chemistry & Biodiversity,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 28, 2025
ABSTRACT
This
study
was
undertaken
to
assess
the
antioxidant
and
neuropharmacological
potentials
of
methanol
leaf
extract
Acanthus
ebracteatus
(MAEL)
through
experimental
in
silico
methods.
The
phytochemical
screening
(PS)
GC–MS
(gas
chromatography–mass
spectrometry)
identified
28
phytochemicals
with
different
classes
nature
MAEL.
MAEL
revealed
better
activity
various
vitro
assays.
Additionally,
tail
suspension
test
(TST)
forced
swimming
(FST),
a
dose‐dependent
reduction
immobility
time
observed
indicating
antidepressant
activity.
In
elevated
plus
maze
(EPM),
led
increased
spent
more
entries
open
arms.
At
same
time,
hole
board
(HBT)
demonstrated
an
increase
head
dipping
compared
control,
both
anxiolytic
Moreover,
locomotor
activities
field
(OFT)
cross
(HCT).
Molecular
docking
showed
binding
affinities
two
compounds,
CID‐518982
CID‐236641.
ADME/T
analysis
good
drug
likeliness
no
toxicity.
Finally,
simulation
structural
stability
significant
fluctuations
compounds
selected
receptors.
this
study,
CID‐236641
might
serve
as
candidates
for
treating
anxiety
depression.
Language: Английский
Comprehensive profiling and therapeutic potential of Nypa fruticans Leaves: Unveiling analgesic and anti-inflammatory properties via in vivo and in silico approaches
Farhana Islam,
No information about this author
Fariya Islam Rodru,
No information about this author
Jannatul Ferdous
No information about this author
et al.
Biocatalysis and Agricultural Biotechnology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 103558 - 103558
Published: March 1, 2025
Language: Английский
Pan-cancer analysis of CDC7 in human tumors: Integrative multi-omics insights and discovery of novel marine-based inhibitors through machine learning and computational approaches
Computers in Biology and Medicine,
Journal Year:
2025,
Volume and Issue:
190, P. 110044 - 110044
Published: March 22, 2025
Language: Английский
Binding interaction of acetylcholinesterase with steroidal pregnanes: insight from machine learning and atomistic simulation
Journal of Biomolecular Structure and Dynamics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 27
Published: March 26, 2025
Acetylcholinesterase
(AChE)
inhibition
is
a
key
strategy
in
the
treatment
of
Alzheimer's
disease
and
other
neurodegenerative
disorders.
While
pregnane-based
compounds
have
been
suggested
as
AChE
inhibitors,
their
mechanism
action
remains
unclear.
This
study
employed
machine
learning
(ML)
molecular
modeling
to
probe
interaction
with
steroidal
pregnanes.
The
ML
models
were
trained
validated
on
bioactivity
datasets
predict
pIC50
pKi
values
small-molecule
compounds.
Among
tested,
Random
Forest
Regressor
demonstrated
superior
performance
was
used
identify
pregnanes
≥
5
7
promising
inhibitors.
Molecular
docking
revealed
strong
interactions
between
several
pregnanes,
particularly
21-[(3-Hydroxy-2-naphthyl)oxy]pregnane-2-one.
compound
interacted
critical
sub-sites
within
binding
gorge,
including
catalytic
active
site,
peripheral
anionic
oxyanion
hole,
sub-site,
through
multiple
hydrogen
bonds
hydrophobic
interactions.
dynamics
simulations
over
100
ns
indicated
structural
stability
conformational
flexibility
representative
AChE-pregnane
complexes
by
dynamic
parameters
cluster
patterns.
Mechanics
Generalized
Born
Surface
Area
free
energy
analysis
confirmed
affinities,
while
residual
decomposition
provided
insights
into
residue
contributions.
Additionally,
favorable
blood-brain
barrier
permeability
drug-like
properties,
suggesting
potential
neurotherapeutic
agents.
Given
predicted
bioactivity,
AChE,
identified
warrant
further
optimization
experimental
evaluation
for
development
safe
effective
Language: Английский
Salacia fruticosa methanol extract pretreatment attenuates scopolamine-induced cognitive decline and Alzheimer's disease-related pathology in zebrafish
Asian Pacific Journal of Tropical Biomedicine,
Journal Year:
2025,
Volume and Issue:
15(3), P. 109 - 118
Published: March 1, 2025
Objective:
To
examine
the
effect
of
methanolic
extract
Salada
fruticosa
in
a
zebrafish
model
scopolamine-induced
Alzheimer’s
disease.
Methods:
High-resolution
liquid
chromatography-mass
spectrometry
was
used
to
characterize
phytochemical
constituents
extract.
The
drug-likeness
these
compounds
determined
via
DruLiTo
tool,
and
their
acetylcholinesterase
(AChE)
binding
affinities
were
studied
by
molecular
docking.
In
vivo
studies,
adult
treated
with
3.125,
6.25,
12.5
mg/L
for
seven
days
then
immersed
scopolamine
(100
μM/L)
induce
cognitive
deficits.
T-maze
novel
object
recognition
tests
behavioral
studies.
addition,
activities
AChE,
antioxidant
enzymes,
myeloperoxidase
brain
tissue
zebrafish.
Results:
revealed
that
40
phytoconstituents
present
Salacia
fruticosa,
27
met
Lipinski's
rule
five,
indicating
good
drug-likeness.
Some
such
as
stylopine,
p
-coumaroylagmatine,
(-)-heliannuol
E,
demonstrated
high
AChE
affinity.
Moreover,
pretreatment
significantly
mitigated
decline,
indicated
increased
time
spent
at
test,
well
decreased
latency
green
arm
(
P
<
0.001).
also
markedly
lowered
malondialdehyde
levels
activity,
enhanced
glutathione
peroxidase
superoxide
dismutase
0.001)
Histopathological
studies
ameliorated
abnormalities
neuronal
cell
morphology.
Conclusions:
Pretreatment
reduces
impairment,
enhances
antioxidants,
attenuates
oxidative
stress,
highlighting
its
potential
preventive
agent
Language: Английский