The
study
aims
to
synthesize,
characterize,
and
evaluate
a
series
of
novel
compounds
for
their
potential
anticancer
activity
targeting
the
A549
lung
cancer
cell
line.
hydrazonothiazole-based
pyridine
(2a-2o)
were
characterized
through
melting
point
analysis,
1H
NMR,
13C
high-resolution
mass
spectrometry
(HRMS).
Their
physicochemical
properties
evaluated
using
in
silico
tools,
all
found
comply
with
Lipinski's
drug-likeness
rule,
suggesting
favorable
drug-like
characteristics.
Biological
studies
revealed
that
synthesized
exhibited
potent
cytotoxicity
against
line,
several
showing
greater
efficacy
than
standard
drug,
cisplatin.
Selectivity
indices
also
calculated,
revealing
2b,
2c,
2f,
2m
enhanced
selectivity
cells
relative
healthy
cells.
Mechanistic
flow
cytometry
demonstrated
these
induced
apoptosis,
compound
demonstrating
highest
apoptotic
activity.
Mitochondrial
membrane
assay
caspase-3
activation
confirmed
involvement
mitochondrial
pathways
apoptosis
induction.
Furthermore,
MMP-9
enzyme
inhibition
assays
identified
2f
as
most
effective
inhibitor,
molecular
docking
dynamics
simulation
confirming
its
strong
binding
interactions
key
residues
enzyme's
active
site.
Overall,
this
suggests
compounds,
particularly
2m,
hold
promise
agents
further
development
optimization
treatment
cancer.
International Research Journal of Multidisciplinary Technovation,
Год журнала:
2025,
Номер
unknown, С. 198 - 222
Опубликована: Март 30, 2025
In
this
study,
computational
methods
were
employed
to
investigate
the
structural,
vibrational,
chemical
shift,
topological,
thermodynamical,
and
biological
properties
of
2-[1-(2,4-dichlorobenzyl)-1H-indazol-3-yl]propan-2-ol
(DCBIP),
along
with
solvent
effects
on
its
electronic
spectra,
frontier
molecular
orbitals
(FMO),
electrostatic
potential
(MEP)
surfaces.
Molecular
geometry
analysis
identified
seven
bond
types
nine
angles.
Vibrational
confirmed
108
fundamental
modes
associated
OH,
CO,
CH,
CC,
CN,
NN,
CCl,
CH₂,
CH₃
functional
groups.
Chemical
shift
validated
structural
integrity
DCBIP,
deshielding
observed
for
key
carbons
protons
due
electronegative
interactions,
hydrogen
bonding,
inductive
from
chlorine
substituents.
The
consistent
FMO
energy
gap
(4.9797–4.9879
eV)
across
solvents
suggests
minimal
influence,
greater
stability
in
polar
environments.
Natural
orbital
(NBO)
strongest
stabilization
lone
pair
(LP)
N4
donating
antibonding
σ*(C8-C9)
(40.25
kJ/mol),
enhancing
delocalization
indazole
ring.
Mulliken
revealed
O3
as
most
site
C9
electropositive,
while
MEP
maps
nucleophilic
regions
over
electrophilic
sites
aromatic
hydrogens.
specific
heat
capacity
DCBIP
(77.31
cal
mol⁻¹K⁻¹)
reflects
moderate
thermal
absorption,
influenced
by
vibrational
contributions
complex
structure.
Topological
analyses
highlighted
electron
localization
at
atoms
(H32,
H37),
six-membered
rings,
presence
van
der
Waals
interactions
steric
DCBIP.
docking
studies
1EOU
5FDC
demonstrated
strong
binding
affinities
-6.89
kcal/mol
-7.45
kcal/mol,
respectively,
suggesting
an
anticonvulsant
agent.
The
study
aims
to
synthesize,
characterize,
and
evaluate
a
series
of
novel
compounds
for
their
potential
anticancer
activity
targeting
the
A549
lung
cancer
cell
line.
hydrazonothiazole-based
pyridine
(2a-2o)
were
characterized
through
melting
point
analysis,
1H
NMR,
13C
high-resolution
mass
spectrometry
(HRMS).
Their
physicochemical
properties
evaluated
using
in
silico
tools,
all
found
comply
with
Lipinski's
drug-likeness
rule,
suggesting
favorable
drug-like
characteristics.
Biological
studies
revealed
that
synthesized
exhibited
potent
cytotoxicity
against
line,
several
showing
greater
efficacy
than
standard
drug,
cisplatin.
Selectivity
indices
also
calculated,
revealing
2b,
2c,
2f,
2m
enhanced
selectivity
cells
relative
healthy
cells.
Mechanistic
flow
cytometry
demonstrated
these
induced
apoptosis,
compound
demonstrating
highest
apoptotic
activity.
Mitochondrial
membrane
assay
caspase-3
activation
confirmed
involvement
mitochondrial
pathways
apoptosis
induction.
Furthermore,
MMP-9
enzyme
inhibition
assays
identified
2f
as
most
effective
inhibitor,
molecular
docking
dynamics
simulation
confirming
its
strong
binding
interactions
key
residues
enzyme's
active
site.
Overall,
this
suggests
compounds,
particularly
2m,
hold
promise
agents
further
development
optimization
treatment
cancer.
