Molecules,
Journal Year:
2023,
Volume and Issue:
28(7), P. 3203 - 3203
Published: April 4, 2023
Human
health
is
experiencing
several
obstacles
in
the
modern
medical
era,
particularly
cancer.
As
a
result,
cancer
therapeutic
arsenal
should
be
continually
expanded
with
innovative
small
molecules
that
preferentially
target
tumour
cells.
In
this
study,
we
describe
development
of
two
molecule
series
(7a-d
and
12a-e)
based
on
1-benzyl-5-bromoindolin-2-one
scaffold
connected
through
hydrazone
linker
to
4-arylthiazole
(7a-d)
or
4-methyl-5-(aryldiazenyl)thiazole
(12a-e)
moiety.
The
anticancer
activity
all
reported
indolin-2-one
derivatives
was
assessed
against
breast
(MCF-7)
lung
(A-549)
cell
lines.
4-arylthiazole-bearing
7c
7d
revealed
best
toward
MCF-7
cells
(IC50
=
7.17
±
0.94
2.93
0.47,
respectively).
Furthermore,
VEGFR-2
inhibitory
for
evaluated.
Both
disclosed
good
activity,
their
IC50
values
were
equal
0.728
µM
0.503
µM,
respectively.
Additionally,
impacts
cycle
phases
as
well
levels
different
apoptotic
markers
(caspase-3,
caspase-9,
Bax,
Bcl-2)
assessed.
Molecular
docking
dynamic
simulations
are
carried
out
explore
binding
mode
within
active
site.
RSC Advances,
Journal Year:
2022,
Volume and Issue:
12(48), P. 31466 - 31477
Published: Jan. 1, 2022
Microbial
Multidrug
Resistance
(MDR)
is
an
emerging
global
crisis.
Derivatization
of
natural
or
synthetic
scaffolds
among
the
most
reliable
strategies
to
search
for
and
obtain
novel
antimicrobial
agents
treatment
MDR
infections.
Here,
we
successfully
manipulated
synthetically
flexible
isatin
moieties
synthesize
22
thiazolyl-pyrazolines
hybrids,
assessed
their
potential
activities
in
vitro
against
various
pathogens,
using
broth
microdilution
calorimetric
XTT
reduction
method.
We
chose
5
strains
represent
major
microorganisms,
viz:
Methicillin-resistant
S.
aureus
(MRSA),
Vancomycin-resistant
E.
faecalis
(VRE)
as
Gram-positive
bacteria;
Carbapenem-resistant
K.
pneumonia
(CRKP),
Extended-spectrum
beta-lactamase
coli
(ESBL-E),
Gram-negative
Fluconazole-resistant
C.
albicans
(FRCA),
a
yeast-like
unicellular
fungus.
The
cytotoxicity
compounds
9f
10h
towards
mammalian
lung
fibroblast
(MRC-5)
cells
demonstrated
satisfactory
safety
margin
represented
by
relatively
high
IC50
values.
target
showed
promising
anti-MDR
activities,
suggesting
they
are
leads
further
development
vivo
studies.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
37(1), P. 1227 - 1240
Published: April 26, 2022
In
the
current
work,
a
hybridisation
strategy
was
adopted
between
privileged
building
blocks,
benzofuran
and
piperazine,
with
aim
of
designing
novel
CDK2
type
II
inhibitors.
The
hybrid
structures
were
linked
to
different
aromatic
semicarbazide,
thiosemicarbazide,
or
acylhydrazone
tails
anchor
designed
inhibitors
onto
kinase
domain.
compounds
showed
promising
inhibitory
activity.
Compounds
9h,
11d,
11e
13c
potent
activity
(IC50
40.91,
41.70,
46.88,
52.63
nM,
respectively)
compared
staurosporine
56.76
nM).
Moreover,
benzofurans
9e,
13b
antiproliferative
activities
towards
cancer
cell
lines,
non-significant
cytotoxicity
on
normal
lung
fibroblasts
MRC-5
line.
Furthermore,
cycle
analysis
as
well
Annexin
V-FITC
apoptosis
assay
Panc-1
line
performed.
Molecular
docking
simulations
performed
explore
ability
target
adopt
common
binding
pattern
Chemical Biology & Drug Design,
Journal Year:
2022,
Volume and Issue:
100(5), P. 656 - 673
Published: Aug. 13, 2022
Targeted
therapy
has
emerged
to
be
the
cornerstone
of
advanced
cancer
treatment,
allowing
for
more
selectivity
and
avoiding
common
drug
toxicity
resistance.
Identification
potential
targets
having
vital
role
in
growth
survival
cells
got
much
easier
with
aid
recent
advances
high
throughput
screening
approaches.
Various
protein
kinases
came
into
focus
as
valuable
therapy.
Meanwhile,
benzimidazole-based
scaffolds
have
gained
significant
attention
promising
kinase
inhibitors
potency
varied
selectivity.
Great
diversity
these
inspired
medicinal
chemists
inspect
effect
structural
changes
upon
inhibitory
activity
on
molecular
level
through
modeling
studies.
The
present
review
gathers
all
considerable
attempts
develop
compounds;
designed
anticancer
since
2015;
that
target
aurora
kinase,
CDK,
CK2,
EGFR,
FGFR,
VEGFR-2;
allow
further
development
progression
regarding
benzimidazoles.
Molecules,
Journal Year:
2023,
Volume and Issue:
28(7), P. 3203 - 3203
Published: April 4, 2023
Human
health
is
experiencing
several
obstacles
in
the
modern
medical
era,
particularly
cancer.
As
a
result,
cancer
therapeutic
arsenal
should
be
continually
expanded
with
innovative
small
molecules
that
preferentially
target
tumour
cells.
In
this
study,
we
describe
development
of
two
molecule
series
(7a-d
and
12a-e)
based
on
1-benzyl-5-bromoindolin-2-one
scaffold
connected
through
hydrazone
linker
to
4-arylthiazole
(7a-d)
or
4-methyl-5-(aryldiazenyl)thiazole
(12a-e)
moiety.
The
anticancer
activity
all
reported
indolin-2-one
derivatives
was
assessed
against
breast
(MCF-7)
lung
(A-549)
cell
lines.
4-arylthiazole-bearing
7c
7d
revealed
best
toward
MCF-7
cells
(IC50
=
7.17
±
0.94
2.93
0.47,
respectively).
Furthermore,
VEGFR-2
inhibitory
for
evaluated.
Both
disclosed
good
activity,
their
IC50
values
were
equal
0.728
µM
0.503
µM,
respectively.
Additionally,
impacts
cycle
phases
as
well
levels
different
apoptotic
markers
(caspase-3,
caspase-9,
Bax,
Bcl-2)
assessed.
Molecular
docking
dynamic
simulations
are
carried
out
explore
binding
mode
within
active
site.
