Arabian Journal of Chemistry,
Journal Year:
2023,
Volume and Issue:
16(8), P. 104956 - 104956
Published: May 3, 2023
New
thiadiazole
sulfonamide
derivatives
were
designed
as
human
carbonic
anhydrase
inhibitors
(hCAIs)
to
develop
robust
and
novel
anticancer
agents.
Tail
modification
approach
was
considered
in
designing
the
target
compounds
which
synthesized
following
two-step
procedure
starting
from
5-acetyl-3-N-(4-sulfamoylphenyl)-2-imino-1,3,4-thiadiazoline.
Cytotoxic
evaluation
revealed
potent
diazene
derivative
2
with
IC50
1.18
μM,
5.28
μM
7.15
against
MCF-7,
Caco2
HepG-2,
respectively.
Moreover,
dihydroxyphenyl
triazene
5
demonstrated
3.03
5.66
12.50
Caco2,
HepG-2
Similarly,
carbohydrazide
coumarin
18
showed
of
2.00
12.30
HepG2,
Molecular
docking
using
hCAIX
hCAXII
adopted
explain
achieved
cytotoxicity
on
molecular
level
their
silico
ADME
evaluation.
ACS Omega,
Journal Year:
2023,
Volume and Issue:
8(6), P. 5571 - 5592
Published: Feb. 6, 2023
In
recent
years,
molecular
hybridization
strategies
have
developed
into
a
potent
strategy
for
drug
discovery.
A
series
of
novel
thiopyrano[2,3-d]thiazoles
linked
to
the
pyrazole
moiety
was
designed
and
as
anticancer
agents
by
hybridization.
Target
compounds
were
synthesized
characterized
spectroscopic
tools
well
X-ray
crystallography
analysis
in
case
thiopyrano[2,3-d]thiazole
derivative
5a.
The
MTT
assay
used
demonstrate
vitro
efficacy
5a-g
7a-j
on
MCF-7
HePG-2.
results
showed
that
some
cycloadducts
such
bromophenyl-4-thioxo-2-thiazolidinone
3e,
4-methylphenyl
5d,
6-substituted-thiopyrano[2,3-d]thiazoles
7e-j
displayed
good
excellent
IC50
range
10.08
±
1.5
25.95
2.8
μg/mL
against
cell
line
from
7.83
±2.1
13.37
1.2
HePG-2
line.
To
explore
enzymatic
tests
isozymes
hCAIX
hCAXII,
most
promising
eight
with
ranging
2.1
μM
chosen.
Compound
7e
exhibited
an
(0.067
0.003
μM)
similar
standard
AZA
CAIX
(0.059
μM)).
For
CAXII,
compound
7i
had
equal
0.123
0.007
compared
(0.083
0.005
μM).
addition,
using
flow
cytometry,
cycle
apoptosis
studies
performed
two
selective
carbonic
anhydrase
(7e
7i).
An
these
caspase-9
also
examined.
Interestingly,
docking
revealed
successfully
embedded
themselves
active
pockets
CAXII
enzymes
through
different
interactions.
Overall,
thiopyrano[2,3-d]thiazole-pyrazole
hybrids
7i)
suggested
be
inhibitors
CAXII.
Cells,
Journal Year:
2024,
Volume and Issue:
13(22), P. 1924 - 1924
Published: Nov. 20, 2024
Identifying
definitive
biomarkers
that
predict
clinical
response
and
resistance
to
immunotherapy
remains
a
critical
challenge.
One
emerging
factor
is
extracellular
acidosis
in
the
tumor
microenvironment
(TME),
which
significantly
impairs
immune
cell
function
contributes
failure.
However,
acidic
conditions
TME
disrupt
interaction
between
cancer
cells,
driving
tumor-infiltrating
T
cells
NK
into
an
inactivated,
anergic
state.
Simultaneously,
promotes
recruitment
activation
of
immunosuppressive
such
as
myeloid-derived
suppressor
regulatory
(Tregs).
Notably,
acidity
enhances
exosome
release
from
Tregs,
further
amplifying
immunosuppression.
Tumor
thus
acts
"protective
shield,"
neutralizing
anti-tumor
responses
transforming
pro-tumor
allies.
Therefore,
targeting
lactate
metabolism
has
emerged
promising
strategy
overcome
this
barrier,
with
approaches
including
buffer
agents
neutralize
pH
inhibitors
block
production
or
transport,
thereby
restoring
efficacy
TME.
Recent
discoveries
have
identified
genes
involved
(pHe)
regulation,
presenting
new
therapeutic
targets.
Moreover,
ongoing
research
aims
elucidate
molecular
mechanisms
acidification
develop
treatments
modulate
levels
enhance
outcomes.
Additionally,
future
studies
are
crucial
validate
safety
pHe-targeted
therapies
patients.
Thus,
review
explores
regulation
pHe
its
potential
role
improving
immunotherapy.
Molecules,
Journal Year:
2022,
Volume and Issue:
27(23), P. 8287 - 8287
Published: Nov. 28, 2022
Coronavirus
Disease-2019
(COVID-19)
is
a
highly
contagious
disease
caused
by
Severe
Acute
Respiratory
Syndrome-Coronavirus-2
(SARS-CoV-2).
The
World
Health
Organization
(WHO)
classified
the
as
global
public
health
hazard
on
11
March
2020.
Currently,
there
are
no
adequate
measures
to
combat
viral
infections,
including
COVID-19,
and
medication
guidelines
for
management
of
COVID-19
dependent
previous
findings
from
SARS-CoV
MERS-CoV
research.
Natural
products
have
achieved
widespread
acceptance
around
world
means
enhancing
healthcare
prevention.
Plants
potential
source
antiviral
factors
such
flavonoids,
phenolic
acids,
terpenoids,
others.
Some
these
agents
exhibit
broad
spectrum
activity.
This
study
aimed
screen
herbal
leads
possible
inhibitors
SARS-CoV-2
ADP
Ribose
Phosphatase
enzyme
(ARP).
Guggulsterone
was
found
be
stabilized
within
active
site
ARP
molecular
dynamic
simulation
with
very
little
fluctuation
throughout
timeframe
100
ns.
Thus,
guggulsterone
can
further
used
develop
safe
competent
evolving
therapy
against
in
post-preclinical
clinical
trials.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
38(1)
Published: March 20, 2023
In
the
relentless
search
for
new
cancer
treatments,
organoselenium
compounds,
and
carbonic
anhydrase
(CA)
inhibitors
have
emerged
as
promising
drug
candidates.
CA
isoforms
IX
XII
are
overexpressed
in
many
types
of
cancer,
their
inhibition
is
associated
with
potent
antitumor/antimetastatic
effects.
Selenium-containing
particularly
selenols,
been
shown
to
inhibit
tumour-associated
nanomolar
range
since
properties
selenium
atom
favour
binding
active
site
enzyme.
this
work,
two
series
selenoesters
(1a-19a
1b-19b),
which
gathered
NSAIDs,
carbo/heterocycles,
fragments
from
natural
products,
were
evaluated
against
hCA
I,
II,
IX,
XII.
Indomethacin
(17b)
flufenamic
acid
(19b)
analogs
exhibited
selectivity
isoform
low
micromolar
range.
summary,
that
combine
NSAIDs
derived
sources
developed
nonclassical
isoforms.
