Chemistry & Biodiversity,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 23, 2024
Abstract
Human
carbonic
anhydrase
(hCA)
plays
a
vital
role
in
the
development
and
progression
of
tumors
hypoxic
conditions.
Herein
we
report
hCA‐II
hCA‐IX
activities
natural
products
isolated
from
Aloe
vera
(L.)
Burm.f.,
to
know
their
potential
tumors.
These
compounds
(
1
–
10
)
displayed
varying
degrees
inhibition
against
hCA‐IX.
All
showed
potent
activity
with
IC
50
values
range
2.9–29.1
μM.
While
for
hCA‐II,
,
2
5
exhibited
4.7–23.4
The
most
effective
hCA
IX
II
inhibitors,
were
chosen
vitro
mechanism
studies,
revealing
that
they
are
competitive
inhibitors.
Furthermore,
when
tested
cytotoxic
effect
on
BJ
(normal)
cell
line,
all
no
behavior,
while
Prostate
cancer
cells
(PC‐3),
1,
3,
5,
7
9
significant
antiproliferative
activity.
Molecular
docking
was
also
conducted
within
active
sites
observe
binding
capability.
Compounds
both
isozymes
PC‐3
therefore
these
best
choices
further
vivo
studies.
Pharmaceuticals,
Journal Year:
2024,
Volume and Issue:
17(2), P. 216 - 216
Published: Feb. 7, 2024
Breast
cancer
is
a
serious
threat
to
the
health
and
lives
of
women.
Two
novel
series
N′-(2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides
1-(aryl)-3-(6-methylimidazo[2,1-b]thiazol-5-yl)ureas
were
designed,
synthesized
investigated
for
their
anticancer
efficacy
against
MCF-7
breast
cell
line.
Three
compounds
first
showed
potent
activity
toward
with
IC50
in
range
8.38–11.67
µM,
respectively,
as
compared
Sorafenib
(IC50
=
7.55
µM).
N′-(1-butyl-2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazide
inhibited
VEGFR-2
0.33
µM
when
0.09
Furthermore,
this
compound
was
introduced
PCR
assessment,
where
it
increased
Bax,
caspase
8,
9
cytochrome
C
levels
by
4.337-,
2.727-,
4.947-
2.420-fold,
while
decreased
Bcl-2,
anti-apoptotic
gene,
0.359-fold
untreated
control
MCF-7.
This
also
arrested
G2/M
phase
27.07%,
11.31%
induced
early
late
apoptosis
In
addition,
molecular
docking
study
active
site
performed
assess
binding
profile
most
compounds.
Moreover,
ADME
parameters
targeted
evaluated.
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 16, 2025
Carbonic
anhydrases
(CAs)
IX
and
XII
are
crucial
for
the
survival
metastasis
of
solid
tumors
under
hypoxic
conditions.
We
designed
compounds
7a–s,
integrating
triazole
benzenesulfonamide
scaffolds
known
inhibiting
tumor-associated
CAs
IX/XII.
Initial
synthesis
included
7a–e,
followed
by
diversification
with
small
hydrophobic
groups
(7f–m)
hydrophilic
heterocyclic
secondary
amines
(7n–s).
Compounds
were
evaluated
against
CA
II,
IX,
to
assess
activity
selectivity.
Chlorinated
derivative
7l
exhibited
highest
efficacy
(KI
=
0.317
μM)
ditrifluoromethylated
7j
0.081
μM).
Subsequent
testing
on
60
cancer
cell
lines
at
10
μM
revealed
promising
anticancer
activity,
especially
dimethylated
7h
(CA
KI
1.324
μM;
XII,
0.435
μM),
GI50
values
ranging
from
0.361
9.21
μM.
Molecular
docking
analyses
elucidated
binding
mechanisms,
highlighting
potential
inhibitory
actions
compound
XII.
Journal of Biomolecular Structure and Dynamics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 25
Published: March 13, 2025
The
discovery
of
novel,
selective
inhibitors
targeting
CDK2
and
PIM1
kinases,
which
regulate
cell
survival,
proliferation,
treatment
resistance,
is
crucial
for
advancing
cancer
therapy.
This
study
reports
the
design,
synthesis,
biological
evaluation
three
novel
pyrazolo[3,4-b]pyridine
derivatives
(6a-c),
confirmed
via
spectral
analyses.
These
compounds
were
assessed
anti-cancer
activity
against
breast,
colon,
liver,
cervical
cancers
using
MTT
assay.
Among
tested
compounds,
6b
exhibited
superior
efficacy,
with
higher
selectivity
indices
HCT-116
(15.05)
HepG2
(9.88)
compared
to
reference
drug
staurosporine.
Mechanistic
studies
revealed
that
induced
apoptosis
(63.04-fold
increase)
arrested
cycle
at
G0-G1
phase,
highlighting
its
anti-proliferative
effects.
In
an
in-vivo
solid
Ehrlich
carcinoma
(SEC)
mouse
model,
compound
significantly
reduced
tumor
weight
volume,
exceeding
efficacy
doxorubicin.
Additionally,
potently
inhibited
kinases
(IC50:
0.27
0.67
µM,
respectively)
tumor-promoting
TNF-alpha
expression,
as
by
histopathological
immunohistochemical
studies.
Computational
analyses,
including
molecular
docking,
dynamics
simulations,
DFT
calculations,
provided
insights
into
binding
stability
interaction
mechanisms
PIM1,
while
in-silico
pharmacokinetic
toxicity
evaluations
favorable
drug-like
profile
safety.
highlights
a
promising
dual
CDK2/PIM1
inhibitor
potent
selectivity,
paving
way
further
optimization
development
lead
molecule
in
