Pharmaceuticals,
Journal Year:
2023,
Volume and Issue:
16(8), P. 1122 - 1122
Published: Aug. 9, 2023
Diseases
are
evolving
as
living
standards
continue
to
improve.
Cancer
is
the
main
cause
of
death
and
a
major
public
health
problem
that
seriously
threatens
human
life.
Colorectal
cancer
one
top
ten
most
common
malignant
tumors
in
China,
ranking
second
after
gastric
among
gastrointestinal
tumors,
its
incidence
rate
increasing
dramatically
each
year
due
changes
dietary
habits
lifestyle
world’s
population.
Although
conventional
therapies,
such
surgery,
chemotherapy,
radiotherapy,
have
profoundly
impacted
treatment
colorectal
(CRC),
drug
resistance
toxicity
remain
substantial
challenges.
Natural
products,
therapeutic
agents,
considered
safest
alternative
for
treating
CRC.
In
addition,
there
evidence
natural
products
can
induce
apoptosis,
inhibit
cell
cycle
arrest,
reduce
invasion
migration
colon
cells
by
targeting
regulating
expression
function
miRNAs.
Here,
we
summarize
recent
research
findings
on
miRNA-regulation-based
antitumor
mechanisms
various
active
ingredients
highlighting
how
target
miRNA
regulation
prevention
treatment.
The
application
delivery
systems
predictive
disease
biomarkers
also
discussed.
Such
approaches
will
contribute
discovery
new
regulatory
associated
with
pathways
provide
theoretical
basis
developing
novel
drugs
compounds
identifying
targets.
Nature Chemical Biology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 21, 2024
Metabolic
alterations
in
cancer
precipitate
associated
dependencies
that
can
be
therapeutically
exploited.
To
meet
this
goal,
natural
product-inspired
small
molecules
provide
a
resource
of
invaluable
chemotypes.
Here,
we
identify
orpinolide,
synthetic
withanolide
analog
with
pronounced
antileukemic
properties,
via
orthogonal
chemical
screening.
Through
multiomics
profiling
and
genome-scale
CRISPR-Cas9
screens,
orpinolide
disrupts
Golgi
homeostasis
mechanism
requires
active
phosphatidylinositol
4-phosphate
signaling
at
the
endoplasmic
reticulum-Golgi
membrane
interface.
Thermal
proteome
genetic
validation
studies
reveal
oxysterol-binding
protein
OSBP
as
direct
phenotypically
relevant
target
orpinolide.
Collectively,
these
data
reaffirm
sterol
transport
actionable
dependency
leukemia
motivate
ensuing
translational
investigation
probe-like
compound
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 7, 2025
Mitochondria,
as
the
energy
factories
of
cells,
are
involved
in
a
wide
range
vital
activities,
including
cell
differentiation,
signal
transduction,
cycle,
and
apoptosis,
while
also
regulating
growth.
However,
current
pharmacological
treatments
for
stroke
challenged
by
issues
such
drug
resistance
side
effects,
necessitating
exploration
new
therapeutic
strategies.
This
review
aims
to
summarize
regulatory
effects
natural
compounds
targeting
mitochondria
on
neuronal
mitochondrial
function
metabolism,
providing
perspectives
treatment.
Numerous
vitro
vivo
studies
have
shown
that
products
berberine,
ginsenosides,
baicalein
protect
reduce
stroke-induced
damage
through
multiple
mechanisms.
These
apoptosis
modulating
expression
mitochondrial-associated
apoptotic
proteins.
They
inhibit
activation
permeability
transition
pore
(mPTP),
thereby
decreasing
ROS
production
cytochrome
C
release,
which
helps
preserve
function.
Additionally,
they
regulate
ferroptosis,
fission,
promote
autophagy
trafficking,
further
enhancing
protection.
As
multi-target
chemical
agents,
offer
high
efficacy
with
fewer
present
promising
potential
innovative
therapies.
Future
research
should
investigate
effectiveness
safety
these
clinical
applications,
advancing
their
development
strategy
stroke.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(4), P. 2946 - 2963
Published: Feb. 14, 2023
Natural
products
provide
inspiration
and
have
proven
to
be
the
most
valuable
source
for
drug
discovery.
Herein,
we
report
a
scaffold
hybrid
strategy
of
Tanshinone
I
discovery
NLRP3
inflammasome
inhibitors.
36
compounds
were
designed
synthesized,
cheminformatic
analyses
showed
that
these
occupy
unique
chemical
space.
The
biological
evaluation
identified
5j,
12a,
12d
as
inhibitors
with
significant
potency,
selectivity,
drug-likeness.
Mechanistic
studies
revealed
derivatives
could
inhibit
degradation
protein
block
oligomerization
NLRP3-induced
apoptosis-associated
speck-like
proteins,
thus
inhibiting
activation.
In
addition,
water
solubility,
in
vitro
metabolic
stability,
oral
bioavailability
also
greatly
improved
compared
I.
Therefore,
this
protocol
provides
new
structural
evolution
class
potent
Bioactive Materials,
Journal Year:
2023,
Volume and Issue:
27, P. 288 - 302
Published: April 18, 2023
New
antimicrobial
strategies
are
urgently
needed
to
meet
the
challenges
posed
by
emergence
of
drug-resistant
bacteria
and
bacterial
biofilms.
This
work
reports
facile
synthesis
dynamic
covalent
nano-networks
(aDCNs)
composing
antibiotics
bearing
multiple
primary
amines,
polyphenols,
a
cross-linker
acylphenylboronic
acid.
Mechanistically,
iminoboronate
bond
drives
formation
aDCNs,
facilitates
their
stability,
renders
them
highly
responsive
stimuli,
such
as
low
pH
high
H2O2
levels.
Besides,
representative
A1B1C1
networks,
composed
polymyxin
B1(A1),
2-formylphenylboronic
acid
(B1),
quercetin
(C1),
inhibit
biofilm
Escherichia
coli,
eliminate
mature
biofilms,
alleviate
macrophage
inflammation,
minimize
side
effects
free
polymyxins.
Excellent
eradication
inflammation
amelioration
efficiency
networks
also
observed
in
peritoneal
infection
model.
The
synthesis,
excellent
performance,
biocompatibility
these
aDCNs
potentiate
much-needed
alternative
current
pipelines.
Nature Chemistry,
Journal Year:
2024,
Volume and Issue:
16(6), P. 945 - 958
Published: Feb. 16, 2024
Abstract
The
efficient
exploration
of
biologically
relevant
chemical
space
is
essential
for
the
discovery
bioactive
compounds.
A
molecular
design
principle
that
possesses
both
biological
relevance
and
structural
diversity
may
more
efficiently
lead
to
compound
collections
are
enriched
in
diverse
bioactivities.
Here
pseudo-natural
product
(PNP)
strategy,
which
combines
PNP
concept
with
synthetic
diversification
strategies
from
diversity-oriented
synthesis,
reported.
collection
was
synthesized
a
common
divergent
intermediate
through
developed
indole
dearomatization
methodologies
afford
three-dimensional
frameworks
could
be
further
diversified
via
intramolecular
coupling
and/or
carbon
monoxide
insertion.
In
total,
154
PNPs
were
representing
eight
different
classes.
Cheminformatic
analyses
showed
structurally
between
Biological
investigations
revealed
extent
bioactivity
enrichment
four
inhibitors
Hedgehog
signalling,
DNA
de
novo
pyrimidine
biosynthesis
tubulin
polymerization
identified
ACS Nano,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 27, 2024
Radiation
therapy,
a
fundamental
treatment
for
tumors,
is
often
accompanied
by
radiation-induced
skin
injury
(RISI).
Excessive
production
of
reactive
oxygen
species
(ROS)
and
subsequent
inflammation
are
two
key
factors
in
RISI
development
that
will
cause
affect
radiotherapy.
Herein,
the
co-assembled
binary
polyphenol
natural
products
inspired
dual-functional
cascade
microneedle
system
prevention
RISI.
Specifically,
epigallocatechin
gallate
(EGCG)
curcumin
(CUR)
were
into
nanoparticles
(CEPG)
intermolecular
interactions
then
incorporated
with
catalase
(CAT)
to
achieve
microneedles
(this
was
conducive
penetrate
epidermal
keratinocytes
where
had
greatest
impact).
When
using
microneedles,
tip
dissolved
rapidly
delivered
CEPG
CAT
dermis,
NPs
able
respond
ROS
decompose
EGCG
CUR.
More
importantly,
formed
converts
superoxide
anions
water
step-by-step,
which
can
reduce
cell
damage
caused
free
radicals
early
stages
radiation
prevention;
meanwhile,
CUR
inhibited
inflammatory
pathways,
achieving
post-radiotherapy
period.
These
explorations
broaden
strategy
application
