Molecular Dynamics Simulation Reveals Structural Insights into Isozyme Selectivity of Carbonic Anhydrase XII Inhibitors in Hypoxic Tumor Microenvironment
Biochemical and Biophysical Research Communications,
Год журнала:
2025,
Номер
753, С. 151471 - 151471
Опубликована: Фев. 11, 2025
Язык: Английский
Rational design of some 1,3,4 trisubstituted pyrazole-thiazole derivatives to serve as MtInhA inhibitors using QSAR, ADMET, Molecular Docking, MM-GBSA, and Molecular Dynamics Simulations approach
Chemical Physics Impact,
Год журнала:
2024,
Номер
9, С. 100769 - 100769
Опубликована: Ноя. 3, 2024
Язык: Английский
Discovery of novel CDK2 inhibitors for cancer treatment: integrating ligand-based pharmacophore modelling, molecular docking, DFT, ADMET, and molecular dynamics simulation studies
Beni-Suef University Journal of Basic and Applied Sciences,
Год журнала:
2024,
Номер
13(1)
Опубликована: Ноя. 25, 2024
Abstract
Background
The
global
landscape
of
public
health
faces
significant
challenges
attributed
to
the
prevalence
cancer
and
emergence
treatment
resistance.
This
study
addresses
these
by
focusing
on
Cyclin-dependent
Kinase
2
(CDK2)
employing
a
systematic
computational
approach
for
discovery
novel
therapeutics.
Results
Initial
ligand-based
pharmacophore
modelling,
utilizing
training
set
five
reported
CDK2
inhibitors,
yielded
robust
model
characterized
Aro|Hyd|
|Acc|Don|
features.
Screening
this
validated
against
ZINC
database
identified
1881
hits,
which
were
further
subjected
molecular
docking
studies.
top
10
compounds
(Z1–Z10)
selected
from
studies
underwent
Pharmacokinetic
parameters
Absorption,
Distribution,
Metabolism,
Excretion
Toxicity
profiling,
Density
Functional
Theory
(DFT)
two
went
100ns
dynamics
(MD)
simulations
comparing
them
with
standard
Roscovitine.
Compounds
Z1
Z2
emerged
as
most
promising,
scores
−
8.05
kcal/mol
8.02
kcal/mol,
respectively.
DFT
analysis
revealed
minimal
variations
in
highest
occupied
orbital–lowest
unoccupied
orbital
energy
gaps,
indicating
consistent
electronic
stability
reactivity
across
candidates.
MD
confirmed
their
stable
interactions
CDK2,
root
mean
square
deviation
(RMSD)
values
ranging
1.4
2.5
Å
1.5
2.4
Z2.
Conclusion
current
research
Z2,
demonstrated
potential
potent
inhibitors
therapy,
providing
valuable
insights
into
development
more
effective
addressing
critical
need
innovative
therapeutic
strategies
treatment.
Graphical
abstract
Язык: Английский
Pyrazolopyrimidine fused Thiazolidinone Hybrids as CDK2 Inhibitors: Insights from Pharmacophore Modeling, Docking, DFT and Molecular Dynamics Simulations.
Journal of Molecular Structure,
Год журнала:
2025,
Номер
unknown, С. 142009 - 142009
Опубликована: Март 1, 2025
Язык: Английский
Synthesis, Characterization, DFT, and in-Silico Analysis of Isoxazole-thiazolidinone Hybrids: Reactivity and Anticancer Potential Assessed through Pharmacological Network, Molecular Dynamics, Molecular Docking, and ADMET Analysis
Journal of Molecular Structure,
Год журнала:
2025,
Номер
unknown, С. 142088 - 142088
Опубликована: Март 1, 2025
Язык: Английский
Synthesis of novel N4-substituted and C2-disubstituted 1,4-benzothiazine-1,1-dioxide derivatives : Integrative computational strategies for breast cancer therapy
Journal of Molecular Structure,
Год журнала:
2025,
Номер
unknown, С. 142310 - 142310
Опубликована: Апрель 1, 2025
Язык: Английский
Exploring Natural Compound Libraries for Breast Cancer Targets: An <i>In Silico</i> Study
Journal of Natural Remedies,
Год журнала:
2025,
Номер
unknown, С. 639 - 656
Опубликована: Апрель 4, 2025
Background:
Breast
cancer
is
a
globally
prevalent,
heterogenous
disease
affecting
both
women
and
men
across
all
ethnic
groups.
It
complex
the
second
most
frequently
diagnosed
solid
tumour
in
worldwide.
The
PI3K/AKT/mTOR
signalling
pathway
plays
significant
role
breast
progression,
survival,
drug
resistance.
dysregulated
approximately
20-34%
of
cases,
making
it
key
target
for
therapeutic
intervention.
Aim:
This
study
aims
to
investigate
potential
natural
compounds
against
using
molecular
docking
studies
evaluate
their
binding
affinity
interactions
with
proteins.
Methods:
Molecular
was
performed
analyse
energy,
conformational
changes,
amino
acid
selected
PI3K
AKT.
Results:
Our
virtual
suggest
that
ginsenoside
(-7.39
kcal/mol),
nimbolide
(-6.22
pristimerin
(-6.28
kcal/mol)
exhibit
strong
affinities
toward
PI3K,
indicating
as
inhibitors.
Additionally,
(-5.52
curcumin
(-5.63
(-6.07
demonstrated
Conclusion:
results
these
AKT,
effective
favourable
may
serve
promising
candidates
targeted
therapy,
especially
patients
PI3K/Akt
dysregulation.
Further
experimental
validation
required
confirm
efficacy.
Major
Findings:
Nimbolide,
pristimerin,
demonstrate
treatment
by
modulating
PI3K/AKT
pathway.
Язык: Английский
Design, Synthesis and Characterization of Novel Thiazolidinone Derivatives: Insights from a Network Pharmacology Approach for Breast Cancer Therapy
Journal of Molecular Structure,
Год журнала:
2024,
Номер
unknown, С. 140915 - 140915
Опубликована: Ноя. 1, 2024
Язык: Английский
Synthesis of novel chalcone/lipoic acid derivatives and cross-linked chitosan for preparation of multi-functional packaging film
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
unknown, С. 138983 - 138983
Опубликована: Дек. 1, 2024
Язык: Английский
Hydroxyl chalcone derivative DK02 as a multi‐target‐directed ligand for Alzheimer's disease: A preclinical study in zebrafish
British Journal of Pharmacology,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 22, 2024
Background
and
Purpose
Alzheimer's
disease
(AD)
is
a
widespread
neurodegenerative
condition
characterized
by
amyloid‐beta
(Aβ)
plaques
tau
protein
aggregates,
leading
to
significant
cognitive
decline.
Existing
treatments
primarily
offer
symptomatic
relief,
underscoring
the
urgent
need
for
novel
therapies
that
address
multiple
AD
pathways.
This
study
evaluates
efficacy
of
DK02,
hydroxyl
chalcone
derivative,
in
scopolamine‐induced
dementia
model
zebrafish,
hypothesizing
it
targets
several
mechanisms
simultaneously.
Experimental
Approach
We
employed
blend
experiments,
including
silico
docking,
vitro
enzyme
inhibition
assays
vivo
zebrafish
models,
assess
therapeutic
effects
DK02.
Methods
included
molecular
docking
forecast
interaction
sites,
acetylcholinesterase
(AChE)
testing,
various
behavioural
histopathological
analyses
gauge
DK02's
neuroprotective
impacts.
Key
Results
DK02
emerged
as
potent
AChE
inhibitor
via
virtual
screening,
significantly
enhanced
functions
improving
memory
retention
reducing
anxiety‐like
behaviours.
also
displayed
strong
antioxidant
properties,
oxidative
stress‐induced
neuronal
damage.
Histopathological
analysis
confirmed
its
showing
decreased
amyloid
plaque
burden
mitigated
structural
brain
Conclusion
Implications
shows
promise
multi‐target‐directed
ligand
AD,
offering
new
path
simultaneously
addressing
cholinergic,
Its
potential
enhance
curtail
neurodegeneration
suggests
advantages
over
current
treatments.
Further
research
into
long‐term
impacts
essential
development
therapy.
Язык: Английский