Cancer Cell International,
Год журнала:
2024,
Номер
24(1)
Опубликована: Дек. 23, 2024
Bioinformatics
models
greatly
contribute
to
individualized
assessments
of
cancer
patients.
However,
considerable
research
neglected
some
critical
technological
points,
including
comparisons
multiple
modeling
algorithms,
evaluating
gain
effects
constructed
model,
comprehensive
bioinformatics
analyses
and
validation
clinical
cohort.
These
issues
are
worthy
emphasizing,
which
will
better
serve
future
research.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(3), С. 351 - 351
Опубликована: Фев. 28, 2025
Background:
Histone
deacetylases
(HDACs)
are
enzymes
that
deacetylate
histone
proteins,
impacting
the
transcriptional
repression
and
activation
of
cancer-associated
genes
such
as
P53
Ras.
The
overexpression
HDACs
in
breast
cancer
(BC)
underscores
their
significance
therapeutic
targets
for
modulating
gene
expression
through
epigenetic
regulation.
Methods:
In
this
study,
a
novel
series
SAHA
(suberoylanilide
hydroxamic
acid)
analogs
were
designed
using
an
silico
ligand-based
strategy.
These
then
synthesized
evaluated
HDAC-inhibitory
capacity
well
antiproliferative
on
cells.
compounds
retained
aliphatic
LINKER,
mimicking
natural
substrate
acetyl-lysine,
while
differing
from
fragment
present
SAHA.
Results:
exhibited
HDAC
inhibitory
activity,
suggesting
potential
binding
to
these
pharmacological
targets.
Compounds
5b,
6a,
6b
identified
promising
candidates
evaluation
cell
lines
MCF-7
MDA-MB-231
at
72
h.
Specifically,
compound
6b,
which
contains
N-trifluoroacetyl
group
zinc-binding
(ZBG),
demonstrated
IC50
76.7
µM
line
45.7
line.
non-tumorigenic
line,
154.6
µM.
Conversely,
almost
negligible
safety
margin
with
regard
its
cytotoxic
activity
when
compared
cells
healthy
(MCF-10A).
This
observation
elevated
toxicity
by
acid-derived
molecules.
Conclusions:
bioisosteric
modification
ZBG
6a
favorable
exhibiting
higher
margin.
study
challenge
identifying
ZBGs
replace
acid
development
inhibitors,
objective
enhancing
physicochemical
toxicological
profile
utilization
BC
treatment.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 21, 2025
Since
decades
after
temozolomide
was
approved,
no
effective
drugs
have
been
developed.
Undoubtedly,
blood–brain
barrier
(BBB)
penetration
is
a
severe
issue
that
should
be
overcome
in
glioblastoma
multiforme
(GBM)
drug
development.
In
this
research,
we
were
inspired
by
linezolid
through
structural
modification
with
several
bioactive
moieties
to
achieve
the
desired
brain
delivery.
The
results
indicated
histone
deacetylase
modification,
referred
as
compound
1,
demonstrated
promising
cytotoxic
effects
various
tumor
cell
lines.
Further
comprehensive
mechanism
studies
1
induced
acetylation,
leading
DNA
double-strand
breaks,
and
ubiquitination
of
RAD51,
disrupting
repair
process.
Furthermore,
also
exhibited
dramatic
improvement
orthotopic
GBM
mouse
model,
demonstrating
its
efficacy
satisfying
BBB
penetration.
Therefore,
reported
provided
an
independent
therapeutic
pathway,
elongation
survival
size
reduction,
ability
penetrate
BBB,
potent
further
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(2), С. 850 - 850
Опубликована: Янв. 20, 2025
Precise
binding
free-energy
predictions
for
ligands
targeting
metalloproteins,
especially
zinc-containing
histone
deacetylase
(HDAC)
enzymes,
require
specialized
computational
approaches
due
to
the
unique
interactions
at
metal-binding
sites.
This
study
evaluates
a
docking
algorithm
optimized
zinc
coordination
determine
whether
it
could
accurately
differentiate
between
protonated
and
deprotonated
states
of
hydroxamic
acid
ligands,
key
functional
group
in
HDAC
inhibitors
(HDACi).
By
systematically
analyzing
both
protonation
states,
we
sought
identify
which
state
produces
poses
energy
estimates
most
closely
aligned
with
experimental
values.
The
was
applied
across
2,
4,
8,
comparing
ligand
correlations
data.
results
demonstrate
that
consistently
yielded
stronger
data,
R2
values
outperforming
counterparts
all
targets
(average
=
0.80
compared
form
where
0.67).
These
findings
emphasize
significance
proper
molecular
studies
zinc-binding
particularly
HDACs,
suggest
deprotonation
enhances
predictive
accuracy.
study’s
methodology
provides
robust
foundation
improved
virtual
screening
protocols
evaluate
large
libraries
efficiently.
approach
supports
streamlined
discovery
high-affinity,
HDACi,
advancing
therapeutic
exploration
metalloprotein
targets.
A
comprehensive,
step-by-step
tutorial
is
provided
facilitate
thorough
understanding
enable
reproducibility
results.
Clinical Epigenetics,
Год журнала:
2025,
Номер
17(1)
Опубликована: Фев. 22, 2025
Epigenetics
is
currently
considered
the
investigation
of
inheritable
changes
in
gene
expression
that
do
not
rely
on
DNA
sequence
alteration.
Significant
epigenetic
procedures
are
involved,
such
as
methylations,
histone
modifications,
and
non-coding
RNA
actions.
It
confirmed
through
several
investigations
associated
with
formation,
development,
metastasis
various
cancers,
colorectal
cancer
(CRC).
The
difference
between
genetic
mutations
former
could
be
reversed
or
prevented;
therefore,
treatment
prevention
achieved
by
restoring
abnormal
events
within
neoplastic
cells.
These
treatments,
consequently,
cause
anti-tumour
effects
augmentation,
drug
resistance
reduction,
host
immune
response
stimulation.
In
this
article,
we
begin
our
survey
exploring
basic
mechanisms
to
understand
tools
strategies
for
treating
monotherapy
combination
chemotherapy
immunotherapy.
European journal of medical research,
Год журнала:
2025,
Номер
30(1)
Опубликована: Март 14, 2025
Spiruchostatin
A
also
referred
to
as
YM753
and
OBP801,
a
cyclic
peptide-based
natural
product
derived
from
Pseudomonas
sp.,
is
distinguished
by
its
potent
inhibition
of
Class
I
histone
deacetylases
(HDACs).
The
modulation
epigenetic
mechanisms
HDAC
inhibitors
fundamental
for
altering
gene
expression
related
cell
growth,
apoptosis,
differentiation,
highlighting
their
potential
in
oncologic
therapies.
This
updated
review
assesses
the
antitumor
efficacy
across
diverse
cellular
animal
models,
scrutinizing
viability
therapeutic
agent
against
various
cancers.
systematic
literature
was
executed
searching
databases
such
PubMed/MedLine,
Scopus,
Web
Science
October
2022
February
2023.
inclusion
criteria
focused
on
studies
involving
context
cancer
treatment,
including
vitro
vivo
models.
concentrated
compound's
mechanistic
action,
biological
activity,
clinical
applicability.
has
demonstrated
significant
activities,
inducing
apoptosis
inhibiting
tumor
growth
effectively
multiple
Its
particularly
noted
synergistic
applications
with
other
anticancer
agents,
enhancing
efficacy.
Mechanistically,
compound
facilitates
chromatin
relaxation
transcriptional
activation
key
suppressor
genes
through
increased
acetylation.
exhibits
substantial
an
effective
subsequent
modifications
biology.
However,
comprehensive
trials
are
imperative
validate
safety
profiles
comprehensively.
Future
research
warranted
elucidate
detailed
molecular
develop
biomarkers
predicting
treatment
response.
Comprehensive
longitudinal
critical
establish
A's
role
within
broader
oncological
regimen,
along
exploration
analogs
improved
outcomes.
APOPTOSIS,
Год журнала:
2024,
Номер
29(11-12), С. 2047 - 2073
Опубликована: Окт. 12, 2024
Triple-negative
breast
cancer
(TNBC)
presents
a
significant
challenge
for
treatment
due
to
its
aggressive
nature
and
the
lack
of
effective
therapies.
This
study
developed
dual
inhibitors
against
cell
division
cycle
25
(CDC25)
histone
deacetylases
(HDACs)
TNBC
treatment.
CDC25
phosphatases
are
crucial
activating
cyclin-dependent
kinases
(CDKs),
master
regulators
progression.
HDACs
regulate
various
biological
processes
by
deacetylating
non-histone
proteins,
affecting
gene
expression,
chromatin
structure,
differentiation,
proliferation.
Dysregulations
HDAC
associated
with
several
human
malignancies.
We
generated
group
combining
molecular
structures
(quinoline-5,8-dione)
(hydroxamic
acid
or
benzamide)
pharmacophores.
The
newly
compounds
were
evaluated
solid-tumor,
leukemia,
non-malignant
epithelial
cells.
Among
synthesized
compounds,
18A
emerged
as
potent
inhibitor,
demonstrating
cytotoxicity
cells,
superior
effects
on
other
types
while
sparing
possessed
similar
inhibitory
activity
MS-275
potently
suppressed
in
vitro
CDK1
dephosphorylation
Additionally,
hindered
progression
S
G
