Abstract
A
novel
series
of
quinoxaline‐linked
fused
oxazole‐imidazole
conjugates
(
7a–n
)
have
been
synthesized.
The
anticancer
activity
these
compounds
was
evaluated
against
two
human
breast
cancer
cell
lines,
MCF‐7
and
MDA‐MB‐231,
using
Erlotinib
as
a
reference
drug,
with
the
MTT
assay
method.
results
showed
that
7g
,
7f
7e
exhibited
significantly
greater
efficacy
compared
to
standard
drug
Erlotinib.
In
survival
test
normal
line
MCF‐10A,
three
potent
were
evaluated,
none
displayed
notable
cytotoxicity,
IC
50
values
than
98.13
#x000B5;M.
Furthermore,
assessed
for
tyrosine
kinase
EGFR
inhibitory
activity,
reference.
in
vitro
revealed
demonstrated
excellent
efficacy,
1.52
±
0.09
µM
1.25
0.08
µ;M,
respectively.
Molecular
docking
studies
also
confirmed
strong
binding
interactions
both
ER‐α.
Additionally,
most
underwent
silico
pharmacokinetic
evaluation
SWISS,
ADME,
pkCSM.
These
complied
five
major
filters
(Lipinski's
rule,
Ghose
Veber
Egan
Muegge
rule)
without
any
violations.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(6), С. 4463 - 4482
Опубликована: Март 12, 2024
Sorafenib,
a
multiple
kinase
inhibitor,
is
widely
used
as
first-line
treatment
for
hepatocellular
carcinoma.
However,
there
need
more
effective
alternatives
when
sorafenib
proves
insufficient.
In
this
study,
we
aimed
to
design
structure
that
surpasses
sorafenib's
efficacy,
leading
us
synthesize
sorafenib–ruthenium
complexes
the
first
time
and
investigate
their
properties.
Our
results
indicate
exhibit
superior
epidermal
growth
factor
receptor
(EGFR)
inhibition
compared
alone.
Interestingly,
among
these
complexes,
Ru3S
demonstrated
high
activity
against
various
cancer
cell
lines
including
sorafenib-resistant
HepG2
cells
while
exhibiting
significantly
lower
cytotoxicity
than
in
healthy
lines.
Further
evaluation
of
cycle,
apoptosis,
antiangiogenic
effects,
molecular
docking,
dynamics
studies
revealed
holds
great
potential
drug
candidate.
Additionally,
free
was
encapsulated
into
polymeric
micelles
M1,
enhanced
on
observed.
Collectively,
findings
position
promising
candidate
EGFR
warrant
further
exploration
development
purposes.
Abstract
This
study
focused
on
the
synthesis
and
evaluation
of
biological
activity
ten
novel
acetohydrazide
hybrid
derivatives,
having
furfuryloxy‐1,2,3‐triazole
ring.
All
target
compounds
were
tested
in
vitro
silico
for
their
inhibitory
potential
against
key
enzymes:
hAChE,
hBChE,
hCAI,
hCAII,
all
involved
significant
physiological
processes.
Remarkably,
two
compounds,
namely
(E)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N′‐(4‐hydroxy‐3‐methoxybenzylidene)acetohydrazide
(9)
(E)‐N′‐(4‐chlorobenzylidene)‐2‐(4‐((furan‐2‐ylmethoxy)methyl)‐1H‐1,2,3‐triazol‐1‐yl)acetohydrazide
(11)
,
exhibited
strong
activity.
Compound
9
emerged
as
top‐performing
inhibitor
both
hAChE
(IC
50
0.23
μM)
hBChE
0.74
μM).
Additionally,
11
displayed
potent
effects
hCAI
with
IC
values
0.18
μM
0.15
μM,
respectively.
Furthermore,
studies
provided
valuable
insights
into
interaction
mechanisms
stability
ligand‐protein
complexes.
demonstrated
binding
scores
−12.063
kcal/mol
−9.359
while
substantial
−7.040
−8.216
hCAII.
In
conclusion,
they
stand
out
promising
inhibitors
hCAII
enzymes.
Their
activity,
supported
by
low
values,
indicated
to
inhibit
enzymes
associated
neurological
metabolic
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 25
Опубликована: Янв. 31, 2024
A
synthesized
azo
compound
based
on
4-amino
antipyrine
and
its
complexes
with
Ni(II)
in
solution
solid
phase
is
reported.
The
structures
of
these
compounds
have
been
testified
by
IR
NMR
spectroscopy.
combined
experimental
theoretical
approach
was
used.
To
study
the
structure
properties
compound,
as
well
possible
complex
formation
Ni(II),
ab
initio
quantum-chemical
calculations
were
carried
out
using
Hartree-Fock
(HF)
method
6-31
G
basis
set
electron
density
functional
theory
(DFT)
hybrid
three-parameter
potential
B3LYP
extended
6-311++G(d,p)
taking
into
account
polarization
diffuse
functions
for
all
atoms.
geometric,
energy,
electronic
parameters
calculated
analyzed.
HOMO-LUMO
energy
gap
has
to
determine
chemical
activity.
Both
had
effective
inhibition
against
butyrylcholinesterase
acetylcholinesterase.
IC50
values
found
19.43
27.08
µM
AChE,
2.37
7.40
BChE,
respectively.
For
anticancer
outcome,
high
doses
E1
inhibited
viability
about
40–45%,
while
this
rate
around
65–70%
E2
at
same
doses.
Anticholinesterase
also
evaluated
silico
techniques.
show
strong
binding
VEGFR1,
exhibiting
superior
inhibitory
activity
hAChE
hBChE
through
shorter
stronger
interactions.
MD
simulations
suggest
that
forms
more
stable
compared
E1,
making
it
a
promising
candidate
further
exploration
anticholinesterase
therapies.
ACS Omega,
Год журнала:
2025,
Номер
10(9), С. 9756 - 9767
Опубликована: Фев. 26, 2025
Polygonum
sivasicum
Kit
Tan
and
Yildiz,
one
of
the
eight
endemic
species
in
Türkiye,
belongs
to
Polygonaceae
family.
Preliminary
phytochemical
investigation
methanol
hexane
extracts
P.
resulted
four
compounds,
namely,
annphenone
(1),
hyperoside
(2),
daucosterol
(3),
β-sitosterol
(4).
Their
structures
were
elucidated
by
1D-,
2D-NMR,
HRESIMS
analyses.
This
study
signifies
first
isolation
from
genus.
Antioxidant
capabilities
different
carried
out
using
DPPH·,
ABTS·+,
CUPRAC,
metal
chelating,
β-carotene
linoleic
acid
bleaching
assays,
their
effectiveness
was
quantified
through
IC50
values.
Furthermore,
27
phenolic
compounds
identified
LC-HRESIMS
extract,
which
has
highest
antioxidant
activity
among
extracts.
The
major
constituents
(4535.0
μg/g
extract),
rutin
(4387.4
chlorogenic
(3306.6
extract).
GC-MS
analysis
determined
palmitic
acid,
α-linolenic
8,11-octadecadieonic
as
fatty
acids
extract.
cell
viability
profile
extract
its
isolates
hyperoside,
annphenone,
evaluated
on
fibroblast
(CCD-1079Sk),
breast
carcinoma
(MCF-7)
lung
(A549)
lines.
Annphenone
exhibited
values
0.25
±
0.01
mg/mL
against
A549
line
0.36
0.02
MCF-7
line.
selective
cytotoxicity
observed
for
line,
with
a
high
selectivity
index
1.44,
underscores
potential
promising
candidate
drug
development.
establishes
framework
integrating
profiling
biological
assays
identify
therapeutic
agents
plants.
