The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention
Cancer Prevention Research,
Год журнала:
2024,
Номер
17(7), С. 289 - 303
Опубликована: Май 7, 2024
Abstract
Cancer
growth
is
dependent
on
angiogenesis,
the
formation
of
new
blood
vessels,
which
represents
a
hallmark
cancer.
After
this
concept
was
established
in
1970s,
inhibition
tumor
development
and
metastases
by
blocking
neoangiogenic
process
has
been
an
important
approach
to
treatment
tumors.
However,
antiangiogenic
therapies
are
often
administered
when
cancer
already
progressed.
The
key
reducing
burden
prevention.
We
noticed
20
years
ago
that
series
possible
chemopreventive
agents
showed
properties
tested
experimental
models.
This
article
reviews
relevant
advances
understanding
rationale
for
targeting
angiogenesis
therapy,
prevention,
interception
recently
investigated
substances
with
activity
may
be
suitable
such
strategies.
Many
compounds,
either
dietary
derivatives
or
repurposed
drugs,
tools
angioprevention.
Such
molecules
have
favorable
safety
profile
likely
allow
prolonged
duration
necessary
efficient
preventive
strategy.
Recent
evidence
mechanisms
use
described
here
food
derivatives,
including
flavonoids,
retinoids,
triterpenoids,
omega
fatty
acids,
carotenoids
from
marine
microorganisms.
As
examples,
number
epigallocatechin,
resveratrol,
xanthohumol,
hydroxytyrosol,
curcumin,
fenretinide,
lycopene,
fucoxanthin,
as
aspirin,
β
blockers,
renin–angiotensin–aldosterone
inhibitors,
carnitines,
biguanides,
reviewed.
Язык: Английский
The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53–MDM2 Modulation
Pharmaceuticals,
Год журнала:
2025,
Номер
18(2), С. 274 - 274
Опубликована: Фев. 19, 2025
The
p53,
often
referred
to
as
the
"guardian
of
genome",
is
a
well-established
tumor-suppressor
protein
that
plays
critical
role
in
regulating
cell
cycle,
DNA
repair,
differentiation,
and
apoptosis,
with
its
activity
primarily
modulated
by
MDM2
(murine
double
minute
2,
also
known
HDM2
humans).
Disrupting
protein-protein
interaction
between
p53
represents
promising
therapeutic
strategy
for
developing
anticancer
agents.
Recent
studies
have
shown
several
spirooxindole-containing
compounds
exhibit
significant
antitumor
properties,
inhibiting
p53-MDM2
interaction.
This
review
provides
an
overview
structure-based
spirooxindoles
could
potential.
It
highlights
findings
from
past
decade
concerning
their
antiproliferative
properties
implications
interfering
discussion
includes
various
analogs
candidates
optimizing
leads
drug
discovery
programs
aimed
at
novel
clinically
effective
Язык: Английский
Indole Compounds in Oncology: Therapeutic Potential and Mechanistic Insights
Pharmaceuticals,
Год журнала:
2024,
Номер
17(7), С. 922 - 922
Опубликована: Июль 10, 2024
Cancer
remains
a
formidable
global
health
challenge,
with
current
treatment
modalities
such
as
chemotherapy,
radiotherapy,
surgery,
and
targeted
therapy
often
hindered
by
low
efficacy
adverse
side
effects.
The
indole
scaffold,
prominent
heterocyclic
structure,
has
emerged
promising
candidate
in
the
fight
against
cancer.
This
review
consolidates
recent
advancements
developing
natural
synthetic
indolyl
analogs,
highlighting
their
antiproliferative
activities
various
cancer
types
over
past
five
years.
These
analogs
are
categorized
based
on
common
types,
supported
biochemical
assays
demonstrating
properties.
In
this
review,
emphasis
is
placed
elucidating
mechanisms
of
action
these
compounds.
Given
limitations
conventional
therapies,
therapeutics
enhanced
selectivity
reduced
effects
critical
focus
oncological
research.
Язык: Английский
Synthesis and anti-tumor activity of new benzofuran-based chalcone derivatives as potent VEGFR-2 inhibitors
RSC Medicinal Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
Cancer
is
one
of
the
most
significant
public
health
problems
worldwide,
and
discovery
development
efficient
VEGFR-2
inhibitors
has
been
a
research
hotspot
in
cancer
treatment.
In
present
work,
series
novel
benzofuran-based
chalcone
derivatives
have
prepared,
Язык: Английский
Development of 3-indolyl substituted phenyl pyrazolo-carboxamide hybrids as potential type II VEGFR-2 inhibitors and in vitro cytotoxicity studies
Bioorganic & Medicinal Chemistry Letters,
Год журнала:
2024,
Номер
117, С. 130070 - 130070
Опубликована: Дек. 12, 2024
Язык: Английский
Development of 3-Indolyl Substituted Phenyl Pyrazolo-Carboxamide Hybrids as Potential Type Ii Vegfr-2 Inhibitors and in Vitro Cytotoxicity Studies
Опубликована: Янв. 1, 2024
Язык: Английский
Design, synthesis, anti‐cancer, anti‐inflammatory and in silico studies of 3‐substituted‐2‐oxindole derivatives
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
21(11)
Опубликована: Июль 30, 2024
Abstract
This
study
focuses
on
the
design
and
synthesis
of
3‐substituted‐2‐oxindole
derivatives
aimed
at
developing
dual‐active
molecules
with
anti‐cancer
anti‐inflammatory
properties.
The
were
designed
diverse
structural
functional
features
while
adhering
to
Lipinski,
Veber,
Leeson
criteria.
Physicochemical
properties
assessed
using
SWISSADME
ensure
drug‐likeness
favourable
pharmacokinetics.
Multistep
synthetic
procedures
employed
for
molecule
synthesis.
In
vitro
evaluations
confirmed
dual
activity
derivatives,
specific
emphasis
significance
dialkyl
aminomethyl
substitutions
potency
against
various
cell
lines.
4
a
exhibited
GI
50
value
3.00E
−05
MDA‐MB‐231,
b
has
shown
2E
c
6E
VERO,
d
8E
each
both
MDA‐MB‐231
MCF‐7
e
values
5E
VERO.
analysis
indicates
that
compounds
3
(71.19
%),
(66.84
g
(63.04
%)
significant
activity.
Additionally,
in
silico
binding
free
energy
interaction
studies
revealed
correlations
between
computational
data,
identifying
,
i
as
promising
candidates.
Key
residues
such
Glu917,
Cys919,
Lys920,
Glu850,
Lys838,
Asp1046
found
play
critical
roles
ligand
kinase
inhibition,
providing
valuable
insights
designing
potent
VEGFR2
inhibitors.
Quantum
Mechanics‐based
Independent
Gradient
Model
further
highlighted
electronic
landscape,
showing
larger
attractive
peaks
higher
electron
density
gradients
compared
Sunitinib,
suggesting
stronger
more
forces.
These
findings
support
potential
these
development
optimization
anticancer
drug
design.
Язык: Английский
Discovery of novel bioactive compounds in Catharanthus roseus exhibiting anti-angiogenic activity against VEGFR-2 TKD for Glioblastoma tumour growth suppression
Опубликована: Дек. 11, 2024
The
progression
of
Glioblastoma
(GBM)
relies
heavily
on
angiogenesis,
the
formation
new
blood
vessels,
facilitated
by
proangiogenic
factors
like
vascular
endothelial
growth
factor
(VEGF)
within
tumor
microenvironment.
VEGF
interacts
primarily
with
its
receptor
VEGFR-2
(VEGF
receptor-2),
making
it
a
key
target
for
anti-angiogenic
therapy.
Existing
agents,
while
effective,
often
pose
cardiovascular
risks,
necessitating
exploration
safer
alternatives.
Plant-based
compounds,
including
those
from
Catharanthus
roseus,
show
promise
in
this
regard.
Despite
known
activity
C.
roseus
extracts,
comprehensive
investigation
into
phytoconstituents
and
their
potential
is
lacking.
This
study
aims
to
fill
gap
employing
silico
methods
screen
safe
novel
compounds
targeting
tyrosine
kinase
domain
(VEGFR-2
TKD).
Utilizing
molecular
docking
ADMET
(absorption,
distribution,
metabolism,
excretion,
toxicity)
tools,
(16R)-Dihydrositsirikine
emerges
as
promising
candidate,
exhibiting
drug-like
properties,
non-toxicity,
binding
affinity
-7.2
kcal/mol
ATP
site
TKD,
greater
than
that
(-6.6
Kcal/mol).
Molecular
Dynamics
(MD)
simulation
further
confirms
stability
(16R)-Dihydrositsirikine-VEGFR-2
TKD
complex,
supported
good
hydrogen-bonding
(H-bonding).
Free
energy
calculations
via
MM-GBSA
corroborate
favourable
free
energy.
In
conclusion,
highlights
effective
agent
GBM
therapy,
paving
way
future
preclinical
clinical
investigations.
Язык: Английский