Abstract
We
synthesized
a
novel
compound
library
featuring
spirooxindole
core
structure
combined
with
various
heterocycles,
including
benzofuran,
benzothiophene,
and
thiophene
scaffolds.
Evaluation
using
MTT
assays
against
HepG2,
4T1,
MDA‐MB‐231
cells
revealed
the
most
potent
candidate,
hybrid
5c
,
an
IC50
of
5
±
0.6
µM
inducing
G2/M
phase
cell
cycle
arrest,
inhibition
wound
healing,
induction
ROS.
Selected
conjugates
exhibited
significant
inhibitory
potential
MDM2,
KD
values
ranging
from
0.0531
to
16.8
µM.
Notably,
salt
analogue
5q
demonstrated
highest
activity
at
K
D
=
53.1
nM.
Molecular
docking
studies
excellent
accommodation
designed
compounds
within
MDM2
receptor.
All
displayed
favorable
ADME
profiles,
suggesting
their
as
lead
for
further
optimization.
Asian Journal of Chemistry,
Год журнала:
2025,
Номер
37(6), С. 1399 - 1414
Опубликована: Май 27, 2025
This
work
explores
carbon-carbon
bond
formation
via
Michael
addition
in
synthesizing
a
novel
spirooxindole-chromene
derivative
(4)
using
click
chemistry,
examining
its
quantum
parameters
and
potential
anticancer
effects.
Spectroscopic
methods,
including
UV-800,
FT-IR
NMR,
were
used
alongside
calculations
(IEFPCM
model)
to
validate
the
molecular
structure.
The
compound
was
optimized
gas
phase
with
6-311++G(d,p)
basis
set
VEDA
employed
for
vibrational
assignments.
Drug-likeness
properties
assessed
ADMET
online
tool.
In
vitro
studies
sixty
human
cancer
cell
lines
indicated
that
4
showed
17.88%
resistance
against
UO-31
renal
cells
at
10–5
M.
Virtual
screening
identified
active
sites
related
proteins
4DRI,
6CZ4
8BR9,
binding
energies
of
-7.76,
-7.3
-6.59
kcal/mol,
respectively.
Ramachandran
plots
favourable
conformations
docking,
blue
areas
representing
optimal
positions.
Ultimately,
may
be
enhanced
efficacy
through
elimination
reactions
primary
amine
position
on
pyrano
ring.
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 11, 2024
Abstract
This
study
explores
new
anti‐inflammatory
agents
by
synthesizing
pyrazoline‐pyridine
hybrids
with
N‐butylsulfonated
covalent
organic
framework
(COF‐SO
3
H)
as
a
recyclable
catalyst,
achieving
excellent
yields
in
just
one
minute.
The
protocol
was
successfully
scaled
up
to
multi‐gram
scale,
highlighting
its
robustness
and
efficiency,
it
operates
without
the
need
for
column
chromatography.
Among
synthesized
hybrids,
compound
5d
,
hybrid
bearing
an
indole
moiety,
emerged
potent
antioxidant
agent.
It
effectively
inhibited
PDE4B
activation
IC
50
value
of
99.38
nM,
adversely
affecting
HEK
cells.
Compound
demonstrated
dual
activity
significantly
reducing
ROS
production
restoring
mitochondrial
health
LPS‐stimulated
A549
cells,
while
also
downregulating
IL‐1β
NF‐ĸB/p65
expression
In
silico
studies
confirmed
’s
strong
binding
PDE4B,
stable
RMSD
RMSF
values,
indicating
potential
effective
inhibitor.
exhibited
favorable
physicochemical
properties,
met
drug‐likeness
criteria,
showed
low
toxicity
predicted
silico.
These
findings
suggest
that
has
significant
therapeutic
agent
inflammatory
diseases
due
activities.
Abstract
We
synthesized
a
novel
compound
library
featuring
spirooxindole
core
structure
combined
with
various
heterocycles,
including
benzofuran,
benzothiophene,
and
thiophene
scaffolds.
Evaluation
using
MTT
assays
against
HepG2,
4T1,
MDA‐MB‐231
cells
revealed
the
most
potent
candidate,
hybrid
5c
,
an
IC50
of
5
±
0.6
µM
inducing
G2/M
phase
cell
cycle
arrest,
inhibition
wound
healing,
induction
ROS.
Selected
conjugates
exhibited
significant
inhibitory
potential
MDM2,
KD
values
ranging
from
0.0531
to
16.8
µM.
Notably,
salt
analogue
5q
demonstrated
highest
activity
at
K
D
=
53.1
nM.
Molecular
docking
studies
excellent
accommodation
designed
compounds
within
MDM2
receptor.
All
displayed
favorable
ADME
profiles,
suggesting
their
as
lead
for
further
optimization.
