Series
of
2-azetidinones
have
been
designed
as
combretastatin
A4
analogues
with
two
substituted
phenyl
rings
connected
by
a
bridge
composed
amidic
carbonyl
and
β-lactam
ring.
The
target
compounds
(7
–
11,
20
23
21
31)
synthesized
characterized
FT-IR,
1H
NMR,
13C
NMR
mass
spectrometry.
anti-proliferative
activity
the
was
investigated
studying
their
effect
on
viability
breast
cancer
cell
line
MCF-7
normal
WRL‑68.
In
terms
IC50
values,
9
21,
were
found
to
be
most
potent
values
34.27
28.86
µM
for
respectively.
Compounds
subjected
detailed
molecular
docking
studies,
optimized
structures
docked
colchicine
binding
site
in
tubulin
(PDB
ID:
4O2B),
obtained
results
indicated
that
these
can
act
antitubulin
agents
excellent
scores
site.
Anti-Infective Agents,
Год журнала:
2024,
Номер
22(4)
Опубликована: Фев. 2, 2024
Background:
The
outbreak
of
COVID-19
caused
by
severe
acute
respiratory
syndrome
coronavirus2
(SARS-CoV-2)
resulted
in
a
widespread
pandemic.
Various
approaches
involved
the
repositioning
antiviral
remedies
and
other
medications.
Several
therapies,
including
oral
treatments,
represent
some
to
adapting
long
existence
In
silico
studies
provide
valuable
insights
throughout
drug
discovery
development
compliance
with
global
efforts
overcome
main
protease
is
an
essential
target
viral
cycle.
Computer-aided
design
accelerates
identification
potential
therapy.
Aims:
This
work
aims
identify
SARS-CoV-2
inhibitors
using
different
aspects
approaches.
Methods:
this
work,
we
conducted
hierarchical
virtual
screening
inhibitors.
A
similarity
search
was
screen
molecules
similar
inhibitor
PF-07321332.
Concurrently,
structure-based
pharmacophores,
besides
ligand-based
were
derived.
drug-likeness
filter
filtered
compounds
retrieved
from
pharmacophore
modeling
before
being
subjected
molecular
docking.
candidate
that
showed
higher
affinity
than
reference
further
absorption,
distribution,
metabolism,
excretion
(ADME)
parameters.
Results:
According
binding
ADME
analysis,
four
(CHEMBL218022,
PubChem163362029,
PubChem166149100,
PubChem
162396459)
prioritized
as
promising
hits.
above
not
reported
before;
no
previous
experimental
bioactive
assays
are
available.
Conclusion:
Our
time-saving
approach
represents
strategy
for
discovering
novel
SARS-CoV-
2
ultimate
hits
may
be
nominated
leads
International Journal of Applied Pharmaceutics,
Год журнала:
2024,
Номер
unknown, С. 99 - 104
Опубликована: Фев. 15, 2024
Objective:
One
substance
found
in
the
leaves
of
Garcinia
cowa
Roxb
that
has
anticancer
properties
is
garcinisidone-A.
The
study
aims
to
simulate
docking
garcinisidone-A
(Gar-A),
molecular
dynamics,
and
predict
ADME
by
predicting
binding
HER2
protein
breast
cancer
cells
developing
new
drug
candidate
options
for
treatment,
often
starting
with
computational
analysis.
Methods:
research
method
involves
utilization
pkCSM
applications,
Gar-A
simulation
using
Gnina
software
version
1.0.2,
dynamics
conducted
GROMACS
2022.2
CHARMMGUI
applications.
Results:
a
weight
less
than
500,
Log
P
value
greater
5,
limited
amount
water
solubility,
low
level
skin
permeability,
good
intestinal
Convolutional
Neural
Network
(CNN)
pose
score
on
0.6178.
It
also
does
not
readily
cross
blood-brain
barrier,
total
clearance
values
indicate
rapid
elimination
via
other
excretory
routes
or
enzyme
metabolism.
thought
have
interactions
HER2.
There
are
hydrogen
bond
amino
acids
Lys753
Asp863,
carbon-hydrogen
bonds
Leu785,
Ser783,
Thr862,
alkyl
Leu726,
Leu852,
Ile767.
stability
Gar-A-substrate
interaction
could
been
more
evident
during
100
ns
simulation.
Conclusion:
physicochemical
align
Lipinski's
rule
candidates.
predictions
permeability
Gar-A;
however,
it
suggests
cannot
penetrate
barrier.
results
reveal
close
one
which
indicates
similar
action
its
natural
ligand
simulations
stable.
illustrate
potential
as
anticancer.
Series
of
2-azetidinones
have
been
designed
as
combretastatin
A4
analogues
with
two
substituted
phenyl
rings
connected
by
a
bridge
composed
amidic
carbonyl
and
β-lactam
ring.
The
target
compounds
(7
–
11,
20
23
21
31)
synthesized
characterized
FT-IR,
1H
NMR,
13C
NMR
mass
spectrometry.
anti-proliferative
activity
the
was
investigated
studying
their
effect
on
viability
breast
cancer
cell
line
MCF-7
normal
WRL‑68.
In
terms
IC50
values,
9
21,
were
found
to
be
most
potent
values
34.27
28.86
µM
for
respectively.
Compounds
subjected
detailed
molecular
docking
studies,
optimized
structures
docked
colchicine
binding
site
in
tubulin
(PDB
ID:
4O2B),
obtained
results
indicated
that
these
can
act
antitubulin
agents
excellent
scores
site.