Identification of Natural Phytochemicals as AKT2 Inhibitors Using Molecular Docking and Dynamics Simulations as Potential Cancer Therapeutics
Jibon Kumar Paul,
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Mahir Azmal,
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Md. Naimul Haque Shohan
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et al.
Heliyon,
Journal Year:
2025,
Volume and Issue:
11(2), P. e41897 - e41897
Published: Jan. 1, 2025
The
PI3K/AKT/mTOR
pathway
is
central
in
regulating
key
cellular
processes
such
as
proliferation,
survival,
metabolism,
and
angiogenesis.
Dysregulation
of
this
pathway,
particularly
the
AKT2
isoform,
commonly
observed
cancers
breast,
ovarian,
pancreatic
cancers,
leading
to
enhanced
tumor
progression,
metastasis,
therapeutic
resistance.
Therefore,
targeting
for
inhibition
a
promising
strategy
cancer
therapy.
This
study
utilized
molecular
docking
dynamics
simulations
identify
natural
phytochemicals
that
inhibit
AKT2.
Molecular
results
revealed
millettone
(CID
442810)
exhibited
highest
binding
affinity
AKT2,
with
score
-9.5
kcal/mol,
followed
by
uzarigenin
92760),
dihydrobiochanin
A
439784),
abyssinone
I
442152)
scores
-9.0
-8.9
-8.7
kcal/mol
respectively,
outperforming
control
inhibitor,
ipatasertib
24788740)
-7.56
kcal/mol.
indicated
millettone,
uzarigenin,
demonstrated
strong
affinities
stable
interactions
suggesting
their
potential
agents
involve
hyperactivation.
Notably,
uzarigenin's
superior
stability,
evidenced
its
lower
root
mean
square
deviation
(RMSD),
which
measures
structural
solvent-accessible
surface
area
(SASA),
indicates
compactness,
highlights
promise
potent
inhibitor
Future
vitro
vivo
studies
will
be
crucial
confirm
efficacy
these
inhibitors
reducing
progression
applications.
Given
also
plays
role
neuronal
survival
plasticity,
compounds
may
have
applications
neurodegenerative
diseases
Alzheimer's,
warranting
further
investigation
into
dual
relevance.
Language: Английский
Anticancer Activity of Phytochemicals from Nepalese Plants: A Review of Active Phytochemicals and Screening Methods
Anup Luitel,
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Lalit Mohan Pant,
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Niru Thapa
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et al.
Natural Product Communications,
Journal Year:
2025,
Volume and Issue:
20(3)
Published: March 1, 2025
Medicinal
plants
have
long
been
sought
after
as
a
source
of
potentially
valuable
compounds
to
combat
cancer.
This
review
purposes
that
the
phytochemicals
found
in
Nepalese
medicinal
possess
significant
potential
anticancer
activity,
which
calls
for
methodical
evaluation.
The
study
explores
methodologies
employed
screening
activity
Nepal.
Full-text
original
research
articles
were
searched
on
“Google
Scholar”
and
“PubMed”
using
keywords
“Anticancer”
“Medicinal
plants”.
obtained
plant
species
looked
over
National
Herbarium
Plant
Laboratories
(KATH)
Database
confirm
their
existence
A
list
71
showing
was
obtained.
Active
methods
reported
then
analysed.
contained
84
bioactive
compounds,
namely
7
alkaloids,
10
polyphenols,
1
saponins,
5
phytosterols,
29
terpenoids,
11
flavonoids,
3
polysaccharides,
18
other
miscellaneous
showed
activities.
Likewise,
77.78%
studies
used
cell
line-based
vitro
experiments
while
6.94%
animal-based
vivo
methods,
remaining
15.28%
combined
both
approaches.
In
particular,
54.51%
papers
multiple
lines,
single
lines.
These
findings
highlight
trend
significance
these
properties.
Language: Английский
Disafynol: A polyacetylene dimer from Centaurea schmidii enhancing breast cancer cell apoptosis via oxidative and ER stress pathways
Naunyn-Schmiedeberg s Archives of Pharmacology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 28, 2025
Language: Английский
Emerging therapeutic approaches for cholangiocarcinoma: harnessing natural compounds and targeted therapies with proposed cellular mechanism
Deleted Journal,
Journal Year:
2025,
Volume and Issue:
2(1)
Published: March 31, 2025
Language: Английский
An updated review summarizing the anticancer potential of flavonoids via targeting NF-kB pathway
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 6, 2025
Nuclear
factor-κB
(NF-κB)
cell
signaling
pathway
is
essential
for
the
progression
and
development
of
numerous
human
disorders,
including
cancer.
NF-κB
regulates
a
wide
range
physiological
processes,
such
as
survival,
growth,
migration.
Deregulated
NF-kB
resulted
in
unregulated
proliferation,
viability,
movement,
invasion,
thus
promoting
tumor
development.
Recent
findings
have
increasingly
shown
that
plant
derived
phytochemicals
inhibit
potential
to
be
employed
cancer
therapeutics.
Flavonoids
are
group
polyphenolic
natural
compounds
present
various
plants
their
fruits,
vegetables,
leaves.
These
medicinal
properties
owing
antioxidant,
anti-inflammatory,
antiviral,
antitumor
characteristics.
The
main
mechanism
by
which
these
flavonoids
exhibit
anticancer
via
potent
antioxidative
immunomodulatory
actions.
Current
research
reports
demonstrated
exhibited
effects
suppressing
signaling.
Based
on
facts,
we
comprehensively
outlined
role
processes
progression,
drug
resistance,
angiogenesis
metastasis.
In
addition
these,
also
summarize
specifically
targeting
types
cancers.
Language: Английский
A Review of the Most Important Medicinal Plants for Reducing Dental Plaque in Traditional Iranian Medicine
Melika Kakuyi Nezhad,
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Aisan Ghaznavi
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سپیدهدم.,
Journal Year:
2024,
Volume and Issue:
6(1), P. 69 - 75
Published: June 1, 2024
Language: Английский
Effect of fermentation on the constituents in the branches and leaves of Taxus media and non-small cell lung cancer
Xing Guo,
No information about this author
Rui‐Sheng Wang,
No information about this author
Zhenling Zhang
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et al.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Oct. 23, 2024
Introduction
Non-small
cell
lung
cancer
(NSCLC)
is
a
prominent
disease
worldwide.
Currently,
commonly
used
methods,
such
as
surgery
and
radiotherapy,
have
significant
side
effects.
Traditional
Chinese
medicine
(TCM)
has
become
research
hotspot
because
of
its
safe
effective
characteristics.
The
branches
leaves
Taxus
media
are
abundant
in
antitumor
active
compounds,
there
been
no
conducted
yet
regarding
anti–lung
molecular
mechanism.
Objective
aim
this
study
to
investigate
the
activity
two
samples
before
after
fermentation
T.
,
mechanism
inhibitory
effect
on
NSCLC.
Methods
chemical
composition
pre-fermentation
(TM)
post-fermentation
qu
(TMQ)
were
investigated
using
UHPLC-Q-Qrbitrap
HRMS
high-performance
liquid
chromatography
(HPLC).
anti-lung
activities
TM
TMQ
compared
an
A549-induced
tumor
mouse
model.
An
enzyme-linked
immunosorbent
assay
(ELISA),
hematoxylin
eosin
(H&E)
staining,
immunohistochemistry,
immunofluorescence
determine
action.
Results
results
indicated
that
contained
83
consisting
primarily
flavonoids,
organic
acids,
taxanes.
Both
taxanes
flavonoids
higher
than
TM.
effectively
inhibited
growth
non-small
(NSCLC),
inhibition
rate
was
greater
(57.24%)
(49.62%).
administration
downregulated
necrosis
factor-α
(TNF-α),
interleukin-6
(IL-6),
glutathione
(GSH)
level
upregulated
interferon-γ
(IFN-γ),
reactive
oxygen
species
(ROS),
malondialdehyde
(MDA)
levels
serum
mice.
treatment
also
increased
protein
expression
Bax,
Caspase-3,
Beclin-1
tissues.
In
contrast,
bcl-2,
PI3K,
Ki67,
ULK1,
mTOR
suppressed
by
TMQ.
Protein
analyses
reemphasized
superior
over
These
cumulative
findings
demonstrated
action
closely
related
activation
transcriptional
misregulation
pathway
cholinergic
synaptic,
AMPK,
PI3K/Akt/mTOR
signaling
pathways.
Conclusion
This
ingredient
contents
effects
.
addition,
herbal
for
NSCLC
treatment.
Language: Английский