Natural Product Research,
Год журнала:
2024,
Номер
unknown, С. 1 - 8
Опубликована: Янв. 11, 2024
This
study
investigates
the
anti-cancer
potential
of
recently
discovered
indole
alkaloids
from
Nauclea
Officinalis
against
third
and
fourth-generation
EGFR
mutations
using
computational
tools.
Through
ADMET
profiling,
druglikeness
prediction,
docking,
simulations,
we
assessed
their
pharmacokinetics,
binding
interactions,
stability.
Promising
affinity
were
observed,
particularly
for
(±)-19-O-butylangustoline,
which
demonstrated
stronger
both
mutants.
MD
simulations
confirmed
stable
with
(±)-19-O-butylangustoline
exhibiting
highest
These
findings
highlight
these
as
agents,
warranting
further
optimisation
therapeutic
development.
informs
through
insights
into
molecular
properties
energetics.
Future Medicinal Chemistry,
Год журнала:
2023,
Номер
15(14), С. 1233 - 1250
Опубликована: Июль 1, 2023
Background:
VEGFR-2
is
one
of
the
most
effective
targets
in
cancer
treatment.
Aim:
The
design
and
semi-synthesis
new
theobromine
derivatives
as
potential
inhibitors.
Methods:
In
vitro
silico
evaluation
synthesized
compounds.
Results:
Compound
5b
demonstrated
excellent
antiproliferative
inhibitory
effects
with
significant
apoptotic
activity.
It
modulated
immune
response
by
increasing
IL-2
reducing
TNF-α
levels.
Docking
molecular
dynamics
simulations
revealed
compound’s
binding
affinity
VEGFR-2.
Lastly,
computational
absorption,
distribution,
metabolism,
excretion
toxicity
studies
indicated
high
compound
for
drug
development.
Conclusion:
could
be
a
promising
anticancer
agent
targeting
Heliyon,
Год журнала:
2024,
Номер
10(2), С. e24005 - e24005
Опубликована: Янв. 1, 2024
In
this
study,
a
series
of
seven
novel
2,4-dioxothiazolidine
derivatives
with
potential
anticancer
and
VEGFR-2
inhibiting
abilities
were
designed
synthesized
as
inhibitors.
The
compounds
tested
in
vitro
for
their
to
inhibit
the
growth
HepG2
MCF-7
cancer
cell
lines.
Among
tested,
compound
22
(IC50
=
0.079
μM)
demonstrated
highest
anti-VEGFR-2
efficacy.
Furthermore,
it
significant
anti-proliferative
activities
against
2.04
±
0.06
1.21
0.04
M).
Additionally,
also
increased
total
apoptotic
rate
lines
cycle
arrest
at
S
phase.
As
well,
computational
methods
applied
study
VEGFR-2-22
complex
molecular
level.
Molecular
docking
dynamics
(MD)
simulations
used
investigate
complex's
structural
kinetic
characteristics.
DFT
calculations
further
revealed
electronic
properties
22.
Finally,
ADMET
toxicity
tests
performed
indicating
likeness
proposed
be
drugs.
results
suggest
that
displays
promise
an
effective
treatment
can
serve
model
future
modifications
biological
investigations
field.
PLoS ONE,
Год журнала:
2024,
Номер
19(3), С. e0299238 - e0299238
Опубликована: Март 14, 2024
Background
Currently,
there
is
no
antiviral
medication
for
dengue,
a
potentially
fatal
tropical
infectious
illness
spread
by
two
mosquito
species,
Aedes
aegypti
and
albopictus
.
The
RdRp
protease
of
dengue
virus
potential
therapeutic
target.
This
study
focused
on
the
in
silico
drug
discovery
inhibitors.
Methods
To
assess
inhibitory
activity
29
phenolic
acids
from
Theobroma
cacao
L.
against
DENV3-NS5
RdRp,
range
computational
methods
were
employed.
These
included
docking,
drug-likeness
analysis,
ADMET
prediction,
density
functional
theory
(DFT)
calculations,
molecular
dynamics
(MD)
simulations.
aim
these
studies
was
to
confirm
stability
ligand-protein
complex
binding
pose
identified
during
docking
experiment.
Results
Twenty-one
compounds
found
have
possible
activities
DENV
according
data,
they
had
affinity
≥-37.417
kcal/mol
DENV3-
enzyme
as
compared
reference
compound
panduratin
A.
Additionally,
investigation
produced
four
hit
that
subjected
screening
obtain
lead
compound,
catechin.
Based
ELUMO,
EHOMO,
band
energy
gap,
DFT
calculations
showed
strong
electronegetivity,
favouravle
global
softness
chemical
reactivity
with
considerable
intra-molecular
charge
transfer
between
electron-donor
electron-acceptor
groups
MD
simulation
result
also
demonstrated
favourable
RMSD,
RMSF,
SASA
H-bonds
at
pocket
catechin
Conclusion
According
present
findings,
high
sufficient
drug-like
properties
appropriate
profiles.
Moreover,
further
supported
action
candidate.
Therefore,
vitro
vivo
research
cocoa
its
phytochemical
should
be
taken
into
consideration
develop
inhibitor.
RSC Advances,
Год журнала:
2023,
Номер
13(40), С. 27801 - 27827
Опубликована: Янв. 1, 2023
In
this
study,
novel
VEGFR-2-targeting
thiazolidine-2,4-dione
derivatives
with
potential
anticancer
properties
were
designed
and
synthesized.
The
ability
of
the
to
inhibit
VEGFR-2
stop
growth
three
different
cancer
cell
types
(HT-29,
A-549,
HCT-116)
was
examined
