Chemistry - An Asian Journal,
Journal Year:
2023,
Volume and Issue:
19(3)
Published: Dec. 27, 2023
Abstract
Metal
complexes
represented
by
platinum
play
a
very
important
role
in
cancer
treatment
due
to
their
diverse
chemical
structures
and
anti‐tumor
activities.
Recently,
ferroptosis
has
emerged
as
newly
occurring
cell
death
form
the
process.
It
been
reported
that
metal
could
inhibit
proliferation
metastasis
of
tumors
combat
chemotherapy
resistance
targeting
ferroptosis.
In
this
review,
we
briefly
describe
fundamental
process
for
tumor
suppression
triggering
immune
responses.
We
summarize
recent
developments
on
induce
Finally,
outline
prospects
application
based
associated
problems
need
be
solved,
discussed
other
potential
research
directions
complexes.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(5), P. 3843 - 3859
Published: March 5, 2024
To
develop
a
potential
theranostic
metal
agent
to
reverse
the
resistance
of
cancer
cells
cisplatin
and
effectively
inhibit
tumor
growth
metastasis,
we
proposed
design
cyclometalated
iridium
(Ir)
complex
based
on
properties
environment
(TME).
end,
designed
synthesized
series
Ir(III)
2-hydroxy-1-naphthaldehyde
thiosemicarbazone
complexes
by
modifying
hydrogen
atom(s)
N-3
position
compounds
structure
dimers
then
investigated
their
structure–activity
structure–fluorescence
relationships
obtain
an
(Ir5)
with
remarkable
fluorescence
cytotoxicity
cells.
Ir5
not
only
possesses
mitochondria-targeted
but
also
overcomes
inhibits
metastasis
in
vivo.
Besides,
confirmed
anticancer
mechanisms
acting
different
components
TME:
directly
killing
liver
inducing
necroptosis
activating
necroptosis-related
immune
response.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(8), P. 5669 - 5684
Published: April 18, 2023
To
develop
the
next-generation
Pt
drug
with
remarkable
activity
and
low
toxicity
to
maximally
inhibit
tumor
growth,
we
optimized
a
Pt(II)
thiosemicarbazone
compound
(C4)
cytotoxicity
SK-N-MC
cells
then
constructed
new
human
serum
albumin-C4
(HSA-C4)
complex
delivery
system.
The
in
vivo
results
showed
that
C4
HSA-C4
have
therapeutic
efficiency
almost
no
toxicity;
they
induced
apoptosis
inhibited
angiogenesis.
This
system
potential
as
practical
drug.
study
could
pave
way
for
developing
dual-targeted
drugs
achieving
their
targeting
therapy
cancer.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(13), P. 8564 - 8579
Published: June 15, 2023
To
obtain
next-generation
metal
drugs
that
can
overcome
the
deficiencies
of
platinum
(Pt)
and
treat
cancer
more
effectively,
we
proposed
to
develop
a
multitargeted
palladium
(Pd)
agent
tumor
microenvironment
(TME)
based
on
specific
residue(s)
human
serum
albumin
(HSA).
this
end,
optimized
series
Pd(II)
2-benzoylpyridine
thiosemicarbazone
compounds
Pd
(5b)
with
significant
cytotoxicity.
The
HSA-5b
complex
structure
revealed
5b
bound
hydrophobic
cavity
in
HSA
IIA
subdomain
then
His-242
replaced
leaving
group
(Cl)
5b,
coordinating
center.
vivo
results
showed
5b/HSA-5b
had
capacity
inhibiting
growth,
therapeutic
behavior
5b.
In
addition,
confirmed
inhibited
growth
through
multiple
actions
different
components
TME:
killing
cells,
angiogenesis,
activating
T
cells.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(11), P. 7268 - 7279
Published: May 23, 2023
To
integrate
targeted
diagnosis
and
treatment
of
cancer,
we
proposed
to
develop
a
gadolinium
(Gd)
agent
based
on
the
properties
apoferritin
(AFt).
this
end,
not
only
optimized
series
Gd(III)
8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazone
compounds
obtain
compound
(C4)
with
remarkable
T1-weighted
magnetic
resonance
imaging
(MRI)
performance
cytotoxicity
cancer
cells
in
vitro
but
also
constructed
an
AFt–C4
nanoparticle
(NP)
delivery
system.
Importantly,
NPs
improved
targeting
ability
C4
vivo
showed
enhanced
MRI
tumor
growth
inhibition
ratio
relative
alone.
Furthermore,
confirmed
that
inhibited
through
apoptosis,
ferroptosis,
ferroptosis-induced
immune
response.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(7), P. 5744 - 5757
Published: March 29, 2024
To
develop
a
next-generation
metal
agent
and
dual-agent
multitargeted
combination
therapy,
we
developed
copper
(Cu)
compound
based
on
the
properties
of
human
serum
albumin
(HSA)–indomethacin
(IND)
complex
to
remodel
tumor
microenvironment
(TME).
We
optimized
series
Cu(II)
isopropyl
2-pyridyl
ketone
thiosemicarbazone
compounds
obtain
(C4)
with
significant
cytotoxicity
then
constructed
an
HSA–IND–C4
(HSA–IND–C4)
delivery
system.
IND
C4
bind
hydrophobic
cavities
IB
IIA
domains
HSA,
respectively.
In
vivo,
not
only
showed
enhanced
antitumor
efficacy
relative
+
but
also
improved
their
targeting
ability
decreased
side
effects.
The
mechanism
involved
acting
different
components
TME.
inhibited
tumor-related
inflammation,
while
induced
apoptosis
autophagy
cancer
cells
angiogenesis.
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 13, 2025
Glioblastoma
represents
the
most
aggressive
type
of
brain
cancer
with
minimal
clinical
advancements
in
recent
decades
attributed
to
absence
efficient
drug
delivery
strategies.
In
this
study,
we
synthesized
a
series
vanadium
complexes
(V1-V4)
and
then
constructed
lactoferrin
(LF)-V4
nanoparticle
(NP)
system.
The
nanoplatform
crossed
blood-brain
barrier
by
binding
low-density
lipoprotein
receptor-associated
protein-1
selectively
targeted
glioblastoma,
ultimately
inhibiting
growth
situ
glioblastoma
tumors.
LF-V4
NPs
induced
autophagic
cell
death
U87-MG
cells
generating
reactive
oxygen
species
(ROS)
that
damaged
mitochondria.
Further
studies
revealed
triggered
lipid
peroxidation
through
accumulation
ROS,
depletion
GSH,
downregulation
GPX4
SLC7A11,
leading
ferroptosis
cells.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(18), P. 13072 - 13085
Published: Sept. 13, 2023
To
develop
next-generation
metal
drugs
with
high
efficiency
and
low
toxicity
for
targeting
inhibition
of
gastric
tumor
growth
metastasis,
we
not
only
optimized
a
series
ruthenium
(Ru,
III)
2-hydroxy-1-naphthaldehyde
thiosemicarbazone
complexes
to
obtain
Ru(III)
complex
(4b)
remarkable
cytotoxicity
in
vitro
but
also
constructed
4b-decitabine
(DCT)/liposome
(Lip)
delivery
system
(4b-DCT-Lip).
The
vivo
results
showed
that
4b-DCT-Lip
had
stronger
capacity
inhibit
metastasis
than
4b-DCT
addressed
the
co-delivery
problems
improved
their
ability.
Furthermore,
confirmed
mechanism
4b-DCT/4b-DCT-Lip
inhibiting
tumor.
DCT-upregulated
gasdermin
E
(GSDME)
was
cleaved
by
4b-activated
caspase-3
afford
GSDME-N
terminal
then
aggregated
form
nonselective
pores
on
cell
membrane
tumor,
thereby
inducing
pyroptosis
pyroptosis-induced
immune
response.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(17), P. 15606 - 15619
Published: Aug. 15, 2024
For
more
accurate
diagnosis
and
effective
treatment
of
cancer,
we
proposed
to
develop
a
hetero-multinuclear
metal
complex
based
on
the
property
apoferritin
(AFt)
for
targeting
tumor
theranostics
by
integrating
dual-modality
imaging
multimodality
therapy.
To
this
end,
rational
designed
synthesized
trinuclear
Gd(III)–Cu(II)
thiosemicarbazone
(Gd-2Cu)
then
constructed
Gd-2Cu@AFt
nanoparticle
(NP)
delivery
system.
Gd-2Cu/Gd-2Cu@AFt
NPs
not
only
had
significant
T1-weighted
magnetic
resonance
photoacoustic
but
also
effectively
inhibited
growth
through
combination
mild
photothermal
therapy,
chemotherapy,
immunotherapy.
optimized
behavior
therapy
Gd-2Cu,
improved
its
ability,
reduced
side
effects
in
vivo.
Besides,
revealed
clarified
anticancer
mechanism
Gd-2Cu:
interrupting
energy
metabolism
cell,
inducing
apoptosis
activating
systemic
immune
response
immunogenic
cell
death
cancer
cells.
