Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 30, 2024
PROTACs
have
emerged
as
a
therapeutic
modality
for
the
targeted
degradation
of
proteins
interest
(POIs).
Central
to
PROTAC
technology
are
E3
ligase
recruiters,
yet
only
few
them
been
identified
due
lack
ligandable
pockets
in
ligases,
especially
among
single-subunit
ligases.
We
propose
that
binders
partner
ligases
could
be
repurposed
new
recruiters.
MDM2
is
overexpressed
tumors.
Nucleolin
(NCL)
an
protein
displays
similar
tumor-specific
overexpression
pattern
and
nuclear-cytoplasmic
shuttling
role
MDM2.
Furthermore,
NCL
selectively
translocated
on
tumor
cell
surface,
where
it
acts
internalization
receptor
its
binders.
reveal
NCL-binding
Oridonin
(Ori),
natural
ent-kaurene
diterpenoid,
capable
recruiting
by
employing
molecular
bridge.
design
Ori-based
modulating
oncogenic
POIs,
including
BRD4
EGFR.
These
direct
assembly
MDM2-NCL-PROTAC-POI
complexes
induce
proteasomal
POIs
shrinkage.
In
addition
engaged
PROTACs,
MDM2,
along
with
homologue
MDMX,
plays
nonredundant
function
inhibiting
p53
activity.
Dual
inhibition
MDM2/X
proposed
promising
antitumor
strategy.
demonstrate
Ori
also
recruits
MDMX
NCL-dependent
manner.
homo-PROTACs
dual
attenuate
progression.
Our
findings
prove
feasibility
repurposing
recruiters
highlight
potential
recruiter.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(18), P. 3123 - 3123
Published: Sept. 10, 2024
Cancer
remains
one
of
the
most
difficult
diseases
to
treat,
requiring
continuous
research
into
innovative
therapeutic
strategies.
Conventional
treatments
such
as
chemotherapy
and
radiotherapy
are
effective
a
certain
extent
but
often
have
significant
side
effects
carry
risk
resistance.
In
recent
years,
concept
dual-acting
therapeutics
has
attracted
considerable
attention,
particularly
combination
DNA
alkylating
agents
antimicrobial
peptides.
alkylation,
well-known
mechanism
in
cancer
therapy,
involves
attachment
alkyl
groups
DNA,
leading
damage
subsequent
cell
death.
Antimicrobial
peptides,
on
other
hand,
been
shown
be
anticancer
due
their
ability
selectively
disrupt
membranes
modulate
immune
responses.
This
review
aims
explore
synergistic
potential
these
two
modalities.
It
examines
mechanisms
action,
current
findings,
promise
they
offer
improve
efficacy
specificity
treatments.
By
combining
cytotoxic
power
alkylation
with
unique
properties
dual-action
may
new
more
approach
fighting
cancer.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(8), P. 3492 - 3492
Published: April 8, 2025
Plant
extracts
contain
many
small
molecules
that
are
less
investigated.
The
present
paper
aims
to
study
in
silico
physical-chemical,
pharmacokinetic,
medicinal
chemistry
and
lead/drug-likeness
properties
the
ability
interfere
with
activity
of
P-glycoprotein
(P-gp)
transporter
cytochrome
P450
(CYP)
oxidase
system
humans
phloridzin,
phloretin,
4-methylchalcone
metabolic
series
alongside
top
three
compounds
found
ethanolic
extract
from
strawberries
(S),
namely
2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one,
2-pyrrolidinone
5-(cyclohexylmethyl)
hexadecanoic
acid.
phloridzin
derivatives
also
were
studied
for
their
inhibitory
potential
upon
Bcl-2,
TNKS1
COX-2
molecular
targets.
In
vitro,
Caco-2
studies
analyzed
cytoprotective
anti-proliferative
S
(pure
compounds)
comparison
combination
1:1
(GAE/pure
compound,
w/w),
range
1
50
µg
active
per
test
sample.
Altogether,
it
was
concluded
phloretin
(Phl)
can
be
used
alone
or
support
intestinal
cell
health
humans.
Phloridzin
(Phd)
combined
proven
ineffective.
(4-MeCh)
indicated
no
advantages,
while
pure
compound
exhibited
augmented
effects,
becoming
a
candidate
combinations
anticancer
drugs.
Overall,
revealed
possible
limitations
practical
use
due
several
major
CYP
enzymes.
Applied Organometallic Chemistry,
Journal Year:
2025,
Volume and Issue:
39(5)
Published: April 9, 2025
ABSTRACT
Metal
complexes
derived
from
salicylaldehyde‐based
Schiff
bases
are
among
the
frontrunners
in
pursuit
of
precise
and
potent
cancer
treatments
due
to
their
remarkable
prowess.
In
this
study,
base
(
HL
)
was
prepared
via
a
reaction
between
2‐amino‐5‐benzonitrile
salicylaldehyde.
Subsequently,
further
reacted
with
Ni
(II),
Co
Cu
(II)
Pd
ions
using
respective
metal
salts
obtain
homoleptic
mononuclear
C1
–
C4
).
The
composition
were
determined
1
H
13
C
NMR,
UV–Vis,
FTIR,
CHN,
SEM–EDX
HRMS
analyses.
addition,
structural
geometries
,
C3
solid
state
single
crystal
X‐ray
diffraction
analysis
corroborate
mentioned
characterization
techniques
employed.
stability
compounds
assessed
through
time‐dependent
UV–vis
spectroscopy,
revealing
that
C2
exhibited
highest
under
experimental
conditions.
anticancer
effects
tested
on
breast
cell
lines
(MCF‐7)
MTT,
LDH
ATP
assays.
Both
displayed
potential
cytotoxicity
MCF‐7
line,
which
better
inhibition
effect
than
standard
chemotherapeutic
agent,
doxorubicin
(DOX),
IC
50
43.08
μM.
We
postulate
mechanism
by
may
function
is
binding
DNA
=
0.114
(±
0.02)
×
10
4
intercalation
(shown
UV‐CD
UV‐LD
spectroscopy)
at
AT
rich
sites.
These
data
corroborated
silico
extra
precision
(XP)
docking
molecular
dynamic
(MD)
simulations.
