The Journal of Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
89(13), P. 9551 - 9556
Published: June 18, 2024
Because
of
endogenous
signaling
roles
carbon
monoxide
(CO)
and
its
demonstrated
pharmacological
effects,
there
has
been
extensive
interests
in
developing
fluorescent
CO
probes.
Palladium-mediated
insertion
successfully
used
for
such
applications.
However,
recent
years
have
seen
many
publications
using
uncatalyzed
into
a
hydrazone
double
bond
as
way
to
sense
CO.
Such
chemistry
no
precedents
otherwise.
Further,
the
rigor
CO-sensing
work
was
largely
based
on
ruthenium–carbonyl
complexes
CORM-3
surrogates,
which
reported
chemical
reactivity
release
CO2
instead
unless
presence
strong
nucleophile
dithionite.
For
all
these,
it
is
important
reassess
feasibility
CO-insertion
reaction.
By
studying
two
"CO
probes"
gas,
this
study
finds
evidence
bond.
reaction
between
gas
series
eight
compounds
conducted,
leading
same
conclusion.
findings
are
consistent
with
state-of-the-art
knowledge
carbonylation
do
not
support
mechanism
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(12), P. 9789 - 9815
Published: June 12, 2024
Carbon
monoxide
(CO)
is
endogenously
produced
in
mammals,
with
blood
concentrations
the
high
micromolar
range
hemoglobin-bound
form.
Further,
CO
has
shown
therapeutic
effects
various
animal
models.
Despite
its
reputation
as
a
poisonous
gas
at
concentrations,
we
show
that
should
have
wide
enough
safety
margin
for
applications.
The
analysis
considers
large
number
of
factors
including
levels
endogenous
CO,
comparison
to
commonly
encountered
biomolecules
or
drugs,
anticipated
enhanced
profiles
when
delivered
via
noninhalation
mode,
and
amount
data
from
human
clinical
trials.
It
be
emphasized
having
use
does
not
mean
it
benign
safe
general
public,
even
low
doses.
We
defer
latter
public
health
experts.
Importantly,
this
Perspective
written
drug
discovery
professionals
public.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(21), P. 14583 - 14596
Published: Nov. 1, 2023
Carbon
monoxide
has
shown
promise
as
a
therapeutic
agent
against
cancers.
Reactive
oxygen
species
(ROS)-activated
CO
prodrugs
are
highly
demanded
for
targeted
cancer
treatment
but
remain
sporadic.
In
addition,
little
attention
is
on
how
the
release
rate
affects
CO's
biological
effects.
Herein,
we
describe
new
type
of
ROS-activated
metal-free
prodrug,
which
releases
with
tunable
rates
in
response
to
multiple
ROS
and
exhibits
very
pronounced
tumor
suppression
effects
mouse
4t1
breast
model.
Importantly,
first
time,
observe
both
vitro
vivo
that
direct
impact
its
antiproliferative
potency
correlation
between
activity
observed.
aggregates,
our
results
not
only
deliver
ROS-sensitive
also
represent
promising
starting
point
further
in-depth
studies
kinetics
affect
anticancer
activity.
ACS Chemical Biology,
Journal Year:
2024,
Volume and Issue:
19(3), P. 725 - 735
Published: Feb. 10, 2024
With
the
recognition
of
endogenous
signaling
roles
and
pharmacological
functions
carbon
monoxide
(CO),
there
is
an
increasing
need
to
understand
CO's
mechanism
actions.
Along
this
line,
chemical
donors
have
been
introduced
as
CO
surrogates
for
ease
delivery,
dosage
control,
sometimes
ability
target.
Among
all
donors,
two
ruthenium-carbonyl
complexes,
CORM-2
-3,
are
arguably
most
commonly
used
tools
about
20
years
in
studying
actions
CO.
Largely
based
on
data
using
these
CORMs,
has
a
widely
accepted
inference
that
upregulation
heme
oxygenase-1
(HO-1)
expression
one
key
mechanisms
However,
recent
seen
reports
very
pronounced
reactivities
CO-independent
activities
CORMs.
We
interested
examining
question
by
conducting
comparative
studies
gas,
CORM-2/-3,
organic
RAW264.7,
HeLa,
HepG2
cell
cultures.
CORM-3
treatment
showed
significant
dose-dependent
induction
HO-1
compared
"controls,"
while
incubation
6
h
with
250-500
ppm
gas
did
not
increase
protein
mRNA
transcription
level.
A
further
concentration
5%
lead
either.
Additionally,
we
demonstrate
CORM-2/-3
releases
minimal
amounts
under
experimental
conditions.
These
results
indicate
effects
attributable
also
assessed
prodrugs,
BW-CO-103
BW-CO-111.
BW-CO-111
but
dose-dependently
increased
levels
RAW264.7
HeLa
cells.
subsequently
studied
Nrf2-luciferase
reporter
assay,
showing
activity
likely
due
activation
Nrf2
donors.
Overall,
alone
unable
induce
or
activate
various
conditions
vitro.
As
such,
no
evidence
support
attributing
effect
such
culture
This
study
demonstrates
critical
consider
possible
donor
before
observed
biological
It
important
note
