QSAR, ADMET, molecular docking, and dynamics studies of 1,2,4-triazine-3(2H)-one derivatives as tubulin inhibitors for breast cancer therapy
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: July 16, 2024
Abstract
Breast
cancer
remains
a
leading
cause
of
cancer-related
deaths
among
women
globally,
necessitating
the
development
more
effective
therapeutic
agents
with
minimal
side
effects.
This
study
explores
novel
1,2,4-triazine-3(2H)-one
derivatives
as
potential
inhibitors
Tubulin,
pivotal
protein
in
cell
division,
highlighting
targeted
approach
therapy.
Using
an
integrated
computational
approach,
we
combined
quantitative
structure–activity
relationship
(QSAR)
modeling,
ADMET
profiling,
molecular
docking,
and
dynamics
simulations
to
evaluate
predict
efficacy
stability
these
compounds.
Our
QSAR
models,
developed
through
rigorous
statistical
analysis,
revealed
that
descriptors
such
absolute
electronegativity
water
solubility
significantly
influence
inhibitory
activity,
achieving
predictive
accuracy
(R
2
)
0.849.
Molecular
docking
studies
identified
compounds
high
binding
affinities,
particularly
Pred28,
which
exhibited
best
score
−
9.6
kcal/mol.
conducted
over
100
ns
provided
further
insights
into
interactions.
Pred28
demonstrated
notable
stability,
lowest
root
mean
square
deviation
(RMSD)
0.29
nm
fluctuation
(RMSF)
values
indicative
tightly
bound
conformation
Tubulin.
The
novelty
this
work
lies
its
methodological
rigor
integration
multiple
advanced
techniques
pinpoint
promising
potential.
findings
advance
current
understanding
Tubulin
open
avenues
for
synthesis
experimental
validation
compounds,
aiming
offer
new
solutions
breast
treatment.
Language: Английский
Quantum evaluation of novel epoxides: molecular docking, dynamics simulation, pharmacokinetics, stereoselectivity, and mechanistic insights into cis-himachalone and cis-himachalol epoxidation
Ilham Ait braim,
No information about this author
Soukayna Baammi,
No information about this author
Anas Ouled Aitouna
No information about this author
et al.
Chemistry of Heterocyclic Compounds,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 19, 2025
Language: Английский
Design and Optimization of Quinazoline Derivatives as Potent EGFR Inhibitors for Lung Cancer Treatment: A Comprehensive QSAR, ADMET, and Molecular Modeling Investigation
ACS Omega,
Journal Year:
2024,
Volume and Issue:
9(46), P. 45842 - 45857
Published: Nov. 8, 2024
The
epidermal
growth
factor
receptor
(EGFR)
is
part
of
a
protein
family
that
controls
cell
and
development.
Due
to
its
importance,
EGFR
has
been
identified
as
suitable
target
for
creating
novel
drugs.
For
this
research,
we
conducted
2D-QSAR
analysis
on
set
31
molecules
derived
from
quinazoline,
which
exhibited
inhibitory
activity
against
human
lung
cancer.
This
investigation
incorporated
principal
component
(PCA)
multiple
linear
regression
(MLR),
leading
the
development
QSAR
models
with
strong
predictive
capabilities
(
Language: Английский
Receptor tyrosine kinases in breast cancer treatment: unraveling the potential
Qi Yu,
No information about this author
Shumin Deng,
No information about this author
Kuan-Song Wang
No information about this author
et al.
American Journal of Cancer Research,
Journal Year:
2024,
Volume and Issue:
14(9), P. 4172 - 4196
Published: Jan. 1, 2024
Breast
cancer
is
a
multifactorial
disease
driven
by
acquired
genetic
and
epigenetic
changes
that
lead
to
aberrant
regulation
of
cellular
signaling
pathways.
Receptor
tyrosine
kinases
(RTKs),
class
critical
receptors,
are
involved
in
the
initiation
progression
breast
cancer.
RTKs
cell
surface
receptors
with
unique
structures
biological
characteristics,
which
respond
environmental
signals
initiating
cascades
such
as
mitogen-activated
protein
kinase
(MAPK)
pathway,
Janus
(JAK)/signal
transducer,
activator
transcription
(STAT)
phosphoinositide
3-kinase
(PI3K)/AKT
pathway.
The
role
makes
them
suitable
targets
for
treatment.
Targeted
therapies
against
have
been
developed
recent
years,
evaluated
clinical
trials,
approved
several
types,
including
However,
displays
molecular
heterogeneity
exhibits
different
therapeutic
responses
various
drug
leading
limited
effectiveness
targeted
therapy
RTKs.
In
this
review,
we
summarize
structural
functional
characteristics
selected
discuss
mechanisms
current
status
involving
progression.
Language: Английский
Computer‐Aided Design of VEGFR‐2 Inhibitors as Anticancer Agents: A Review
Journal of Molecular Recognition,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 10, 2024
Due
to
its
intricate
molecular
and
structural
characteristics,
vascular
endothelial
growth
factor
receptor
2
(VEGFR-2)
is
essential
for
the
development
of
new
blood
vessels
in
various
pathological
processes
conditions,
especially
cancers.
VEGFR-2
inhibitors
have
demonstrated
significant
anticancer
effects
by
blocking
many
signaling
pathways
linked
tumor
growth,
metastasis,
angiogenesis.
Several
small
compounds,
including
well-tolerated
sunitinib
sorafenib,
been
approved
as
inhibitors.
However,
widespread
side
these
inhibitors-hypertension,
epistaxis,
proteinuria,
upper
respiratory
infection-motivate
researchers
search
with
better
pharmacokinetic
profiles.
The
key
interactions
required
interaction
molecules
protein
target
produce
desired
pharmacological
are
identified
using
computer-aided
drug
design
(CADD)
methods
such
pharmacophore
QSAR
modeling,
structure-based
virtual
screening,
docking,
dynamics
(MD)
simulation
coupled
MM/PB(GB)SA,
other
computational
strategies.
This
review
discusses
applications
inhibitor
design.
Future
designs
may
be
influenced
this
review,
which
focuses
on
current
trends
multiple
screening
layers
Language: Английский