Many
previous
studies
have
demonstrated
that
gold
compounds
possess
successful
results
in
catalysis
and
medicinal
chemistry.
The
central
aim
of
this
dissertation
is
the
design
synthesis
novel
(I)
acyclic
diamino
carbene
complexes
as
a
chemotherapeutic
agent
for
triple-negative
breast
cancer
(TNBC)
catalysis.
In
study,
series
chiral
neutral
cationic
(ADC)
bis-
ADC
been
synthesized.
As
ADCs,
four
diastereomers
S
binaphthyl
L
proline
tertiary
butyl
ester
chloride,
D
R
chloride
synthesized
characterized.
Different
with
bulky
group
different
amine
groups
morpholine,
methyl
ester,
benzyl
After
nitrile
adduct
isonitrile
versions
it
A
bis
All
these
were
tested
biological
activity
against
TNBC
cell
line
MDA-MB-231
adduct,
gave
promising
inhibition
rates.
According
to
Lipinski's
rule,
lipophilicity
determines
effectiveness
drug
absorption
body
through
lipid
membrane.
To
determine
drug-likeness
complexes,
log
P
values
calculated
some
using
modified
shake
flask
method.
Gold
renowned
their
ability
catalysis,
but
enantioselective
not
well
studied.
A3
coupling
reaction
well-known
propargyl
amines.
Here,
has
performed
previously
tertial
ADCs
(SL,
RD,
RL,
SD)
catalyst
expecting
product.
exhibited
reasonable
yields
low
enantiomeric
excess
(ee%).
However,
proof
principle
asymmetric
induction
possible
complexes.
Chemical Reviews,
Год журнала:
2023,
Номер
123(10), С. 6612 - 6667
Опубликована: Апрель 18, 2023
The
gold
drugs,
sodium
thiomalate
(Myocrisin),
aurothioglucose
(Solganal),
and
the
orally
administered
auranofin
(Ridaura),
are
utilized
in
modern
medicine
for
treatment
of
inflammatory
arthritis
including
rheumatoid
juvenile
arthritis;
however,
new
agents
have
been
slow
to
enter
clinic.
Repurposing
different
disease
indications
such
as
cancer,
parasitic,
microbial
infections
clinic
has
provided
impetus
development
complexes
biomedical
applications
based
on
unique
mechanistic
insights
differentiated
from
auranofin.
Various
chemical
methods
preparation
physiologically
stable
associated
mechanisms
explored
biomedicine
therapeutics
or
probes.
In
this
Review,
we
discuss
chemistry
next
generation
which
encompasses
oxidation
states,
geometry,
ligands,
coordination,
organometallic
compounds
infectious
diseases,
inflammation,
tools
biology
via
gold-protein
interactions.
We
will
focus
within
past
decade.
Review
provides
readers
with
an
accessible
overview
utility,
development,
mechanism
action
gold-based
small
molecules
establish
context
basis
thriving
resurgence
medicine.
Medicinal Research Reviews,
Год журнала:
2024,
Номер
44(5), С. 2194 - 2235
Опубликована: Апрель 9, 2024
Abstract
Metal
complexes
based
on
N
‐heterocyclic
carbene
(NHC)
ligands
have
emerged
as
promising
broad‐spectrum
antitumor
agents
in
bioorganometallic
medicinal
chemistry.
In
recent
decades,
studies
cytotoxic
metal–NHC
yielded
numerous
compounds
exhibiting
superior
cytotoxicity
compared
to
cisplatin.
Although
the
molecular
mechanisms
of
these
anticancer
are
not
fully
understood,
some
potential
targets
and
modes
action
been
identified.
However,
a
comprehensive
review
their
biological
is
currently
absent.
general,
apoptosis
caused
by
metal–NHCs
common
tumor
cells.
They
can
cause
series
changes
after
entering
cells,
such
mitochondrial
membrane
(MMP)
variation,
reactive
oxygen
species
(ROS)
generation,
cytochrome
c
(cyt
c)
release,
endoplasmic
reticulum
(ER)
stress,
lysosome
damage,
caspase
activation,
ultimately
leading
apoptosis.
Therefore,
detailed
understanding
influence
cancer
cell
crucial.
this
review,
we
provide
summary
advances
that
trigger
apoptotic
death
via
different
apoptosis‐related
or
signaling
pathways,
including
B‐cell
lymphoma
2
(Bcl‐2
family),
p53,
cyt
c,
ER
thioredoxin
reductase
(TrxR)
inhibition,
so
forth.
We
also
discuss
challenges,
limitations,
future
directions
elucidate
emerging
application
Applied Organometallic Chemistry,
Год журнала:
2024,
Номер
38(4)
Опубликована: Фев. 22, 2024
A
series
of
eight
N
‐heterocyclic
carbenes
(NHC)
gold(I)
complexes,
involving
1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene
(iPr)
ligand
in
combination
with
6‐mercaptopurine
derivatives
(HL
1–8
),
has
been
prepared
and
thoroughly
characterized,
including
elemental
analysis,
mass
spectrometry,
infrared
multinuclear
NMR
spectroscopy,
single
crystal
X‐ray
analysis.
The
showing
general
composition
[Au
(iPr)(L
n
)]
1
–
8
,
were
evaluated
for
their
vitro
cytotoxicity
against
four
human
cancer
cell
lines
A2780
(ovarian)
A2780R
(ovarian
Cisplatin
resistant),
PC3
(prostate)
MCF‐7
(breast),
normal
MRC‐5
cells
(lung
fibroblasts).
complexes
revealed
significant
cytotoxicity,
the
best
IC
50
values
≈
3.4–6.4
μM
reasonable
selectivity.
Cellular
effects
selected
on
using
various
flow
cytometry
assays.
Complexes
3
4
showed
a
strong
pro‐apoptotic
effect
loss
mitochondrial
membrane
potential.
These
findings
indicate
that
major
mechanism
action
is
based
collapse
metabolism
activation
intrinsic
signaling
pathway
apoptosis,
consequently
resulting
death.
only
negligible
production
inflammatory‐related
cytokine
(TNF‐α),
as
well
nuclear
factor
kappa‐light‐chain‐enhancer
activated
B
(NF‐κB)
or
peroxisome
proliferator‐activated
receptor
gamma
(PPARγ).
Moreover,
shotgun
proteomic
analysis
was
performed,
obtained
results
suggest
differs
somewhat
from
Auranofin
.
Organometallics,
Год журнала:
2024,
Номер
43(10), С. 1155 - 1164
Опубликована: Май 7, 2024
The
gold(I)
N-heterocyclic
carbene
(NHC)
complexes,
containing
a
combination
of
1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene
(iPr)
and
the
corresponding
7-azaindole
derivative
(HL1–4),
were
prepared
characterized.
complexes
composition
[Au(iPr)(Ln)],
where
n
=
1–4
for
5-fluoro-7-azaindole
(1),
5-bromo-7-azaindole
(2),
3-chloro-7-azaindole
(3),
3-iodo-7-azaindole
(4),
further
evaluated
their
in
vitro
anticancer
anti-inflammatory
activities.
results
showed
that
(1–4)
behave
as
considerably
cytotoxic
against
human
ovarian
cancer
cell
line
A2780
(with
IC50
≈
4–9
μM)
cisplatin-resistant
A2780R
7–12
μM,
except
2
with
>
25
μM),
providing
significantly
higher
cytotoxicity
than
drug
cisplatin.
Moreover,
they
also
revealed
relatively
good
selectivity
over
normal
cells
(MRC-5),
index
values
SI
2.5.
Complex
4
ability
to
interact
l-cysteine
reduced
glutathione
at
extracellular
intracellular
levels,
respectively.
was
studied
its
cellular
effects
using
flow
cytometry.
influence
activity
pro-inflammatory
transcription
factor
NF-κB
secretion
TNF-α
evaluated,
showing
complex
reveals
comparable
inflammatory
auranofin.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(12), С. 8238 - 8250
Опубликована: Июнь 9, 2023
The
reactivities
of
halido[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I)
(chlorido
(5),
bromido
(6),
iodido
(7)),
bis[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I)
(8),
and
bis[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]dihalidogold(III)
(9),
(10),
(11))
complexes
against
ingredients
the
cell
culture
medium
were
analyzed
by
HPLC.
degradation
in
RPMI
1640
was
studied,
too.
Complex
6
quantitatively
reacted
with
chloride
to
5,
while
7
showed
additionally
ligand
scrambling
8.
Interactions
non-thiol
containing
amino
acids
could
not
be
detected.
However,
glutathione
(GSH)
immediately
5
yielding
(NHC)gold(I)-GSH
complex
12.
most
active
8
stable
under
vitro
conditions
strongly
participated
on
biological
effects
7.
gold(III)
species
9–11
completely
reduced
GSH
are
prodrugs.
All
tested
for
inhibitory
Cisplatin-resistant
cells,
as
well
cancer
stem
cell-enriched
lines
excellent
activity.
Such
compounds
utmost
interest
therapy
drug-resistant
tumors.
