Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies
Future Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown, С. 1 - 13
Опубликована: Фев. 25, 2025
New
triazoloquinazoline
derivatives
were
synthesized
to
explore
their
cytotoxic
activity
on
various
cancer
cell
lines,
prompted
by
the
need
for
effective
anticancer
agents.
All
compounds
confirmed
spectroscopic
methods
and
tested
in
vitro
inhibitory
activities
against
hepatocellular
carcinoma
(HepG-2),
breast
(MCF-7),
prostate
(PC3)
lines.
Ten
VEGFR-2.
Additionally,
studies
investigated
most
active
compound
6,
including
cycle
analysis,
apoptotic
assessment,
effect
gene
expression,
safety
profiling,
molecular
docking,
MD
simulation,
ADMET
analysis.
Compounds
3a,
3c,
6
exhibited
higher
MCF-7
than
doxorubicin.
Compound
was
potent,
arresting
at
G1
phase
showing
proapoptotic
action.
It
significantly
inhibited
VEGFR-2
altered
promoting
BAX,
P21,
P53
while
downregulating
BCL-2.
Docking
simulations
indicated
stable
interaction
with
VEGFR-2,
safety,
profiles
suggested
favorable
drug-likeness
safety.
has
shown
promising
potential,
particularly
cancer,
but
further
research
is
needed
confirm
these
findings
address
long-term
Язык: Английский
Spiroindoline quinazolinedione derivatives as inhibitors of P-glycoprotein: potential agents for overcoming multidrug resistance in cancer therapy
Molecular Diversity,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 19, 2025
Язык: Английский
Chemistry, Synthesis, and Structure Activity Relationship of Anticancer Quinoxalines
Chemistry,
Год журнала:
2023,
Номер
5(4), С. 2566 - 2587
Опубликована: Ноя. 14, 2023
Quinoxaline
is
a
fused
heterocycle
system
of
benzene
ring
and
pyrazine
ring.
It
has
earned
considerable
attention
due
to
its
importance
in
the
field
medicinal
chemistry.
The
extensive
comprehensive
array
biological
activities.
derivatives
have
been
used
as
anticancer,
anticonvulsant,
anti-inflammatory,
antidiabetic,
antioxidant,
antibacterial,
anti-TB,
antimalarial,
antiviral,
anti-HIV,
many
other
uses.
Variously
substituted
quinoxalines
are
significant
therapeutic
agents
pharmaceutical
industry.
This
review
spotlights
on
chemistry,
physiochemical
characters,
synthesis,
products,
chemistry
various
anticancer
quinoxaline
that
were
developed
last
period.
covers
period
from
2016
2023.
Язык: Английский
New vatalanib analogs: design, synthesis, in silico study and biological evaluation for anticancer activity
Journal of Molecular Structure,
Год журнала:
2024,
Номер
1322, С. 140595 - 140595
Опубликована: Ноя. 3, 2024
Язык: Английский
Design, Synthesis, and Biological Evaluation of Novel Quinazoline Derivatives Possessing a Trifluoromethyl Moiety as Potential Antitumor Agents
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
21(5)
Опубликована: Апрель 11, 2024
Abstract
A
novel
series
of
trifluoromethyl‐containing
quinazoline
derivatives
with
a
variety
functional
groups
was
designed,
synthesized,
and
tested
for
their
antitumor
activity
by
following
pharmacophore
hybridization
strategy.
Most
the
20
compounds
displayed
moderate
to
excellent
antiproliferative
against
five
different
cell
lines
(PC3,
LNCaP,
K562,
HeLa,
A549).
After
three
rounds
screening
structural
optimization,
compound
10
b
identified
as
most
potent
one,
IC
50
values
3.02,
3.45,
3.98
μM
PC3,
K562
cells,
respectively,
which
were
comparable
effect
positive
control
gefitinib.
To
further
explore
mechanism
action
cancer,
experiments
focusing
on
apoptosis
induction,
cycle
arrest,
migration
assay
conducted.
The
results
showed
that
able
induce
prevent
tumor
migration,
but
had
no
cells.
Язык: Английский
Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers
Future Medicinal Chemistry,
Год журнала:
2024,
Номер
16(24), С. 2583 - 2598
Опубликована: Ноя. 14, 2024
Nicotinamide-based
VEGFR-2
inhibitors
have
good
contribution
in
drug
discovery.
Язык: Английский
Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies
Pharmaceuticals,
Год журнала:
2023,
Номер
16(9), С. 1303 - 1303
Опубликована: Сен. 15, 2023
Structural-based
drug
design
and
solvent-free
synthesis
were
combined
to
obtain
three
novel
series
of
5-arylethylidene-aminopyrimidine-2,4-diones
(4,
5a-c,
6a,b),
5-arylethylidene-amino-2-thiopyrimidine-4-ones
(7,8),
6-arylpteridines
(9,10)
as
dual
BRD4
PLK1
inhibitors.
MTT
assays
synthesized
compounds
against
breast
(MDA-MB-231),
colorectal
(HT-29),
renal
(U-937)
cancer
cells
showed
excellent-to-good
cytotoxic
activity,
compared
Methotrexate;
MDA-MB-231
the
most
sensitive
cells.
The
active
tested
normal
Vero
Compounds
4
7
significantly
inhibited
PLK1,
with
IC50
values
0.029,
0.042
µM,
0.094,
0.02
respectively,
which
are
nearly
comparable
volasertib
(IC50
=
0.017
0.025
µM).
Compound
triggered
apoptosis
halted
cell
growth
at
G2/M
phase,
similarly
volasertib.
It
also
upregulated
BAX
caspase-3
markers
while
downregulating
Bcl-2
gene.
Finally,
fitted
binding
site
ideal
drug-like
properties
pharmacokinetics,
making
them
promising
anticancer
candidates.
Язык: Английский
DUAL INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) AND TRYPTOPHAN-2,3-DIOXYGENASE (TDO) AS ANTI-TUMOR IMMUNE MODULATORS
Al-Azhar Journal of Pharmaceutical Sciences/Al-Azhar Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
69(1), С. 38 - 61
Опубликована: Март 1, 2024
Indoleamine-2,3-dioxygenase
(IDO)
and
tryptophan-2,3-dioxygenase
(TDO)
are
enzymes
that
catalyze
the
rate-limiting
step
of
kynurenine
pathway.
Recent
literature
reports
IDO
TDO
upregulation
in
tumor
cells
leading
to
L-tryptophan
depletion
accumulation
tryptophan
metabolites.
This
process
represents
an
essential
mechanism
for
tumor-induced
immunosuppression.
Following
failure
Epacadostat,
inhibitor,
phase
3
clinical
trials,
numerous
studies
have
shifted
a
dual
inhibition
scheme
overcome
compensation
linked
TDO.
Therefore,
using
single
molecule
emerges
as
highly
promising
therapeutic
approach.
comprehensive
review
aims
discuss
successful
scaffolds
reported
inhibitors
their
inhibitory
values
against
both
enzymes.
The
active
compounds
potential
form
novel
chemical
class
anti-tumor
immune
modulator
drugs.
Язык: Английский
VEGFER-2 INHIBITORS AND QUINAZOLINE-BASED ANTICANCER AGENTS
Helmy Sakr,
Islam Otify,
Rezk R. Ayyad
и другие.
Al-Azhar Journal of Pharmaceutical Sciences/Al-Azhar Journal of Pharmaceutical Sciences,
Год журнала:
2023,
Номер
68(2), С. 111 - 129
Опубликована: Сен. 1, 2023
Inhibitors
of
vascular
endothelial
growth
factor
receptor
-2
(VEGFR-2)
are
crucial
biological
targets
for
the
development
novel
anticancer
medications.
Quinazoline
also
plays
an
important
role
as
one
building
elements
numerous
drugs.
Thus,
a
review
literature
on
VEGFR-2
inhibitors
and
Quinazoline-based
medicines
has
been
completed.
We
introduced
now
undergoing
clinical
evaluation,
such
Gefitinib,
Erlotinib,
Vandetanib,
Afatinib,
Lenvatinib,
Cabozantinib,
Sorafenib
Regorafenib
in
our
survey.
Additionally,
that
under
were
introduced.
Язык: Английский