Abstract
Fourteen
novel
Chalcone‐Cu
complexes
were
effectively
synthesized
in
this
work.
The
newly
assessed
for
their
effects
on
human
carbonic
anhydrase
isoenzymes
I
and
II,
acetylcholinesterase
enzymes,
antioxidant
activity.
intricate
compounds
exhibited
Ki
values
ranging
from
41.65–190.42
nM
against
hCA
I,
15.79–259.07
14.36–175.73
AChE
enzymes.
These
demonstrated
potent
inhibitory
profiles
the
specified
metabolic
surpassing
of
acetazolamide
(for
II)
tacrine
AChE).
properties
using
DPPH
ABTS
radical
scavenging
assays,
revealing
that
had
moderate
to
high
efficacy
neutralizing
free
radicals.
All
underwent
molecular
docking
experiments.
Compounds
14
,
22
23
yielded
highest
scores.
Compound
a
score
−6.414
kcal/mol
hCAI,
whereas
compound
attained
−6.697
II.
most
favorable
−9.645
AChE.
acquired
results
have
potential
help
towards
development
new
drugs
containing
Cu
complex
structures
treatment
prevalent
ailments
such
as
glaucoma
Alzheimer's
diseases.
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.
Molecules,
Год журнала:
2024,
Номер
29(8), С. 1857 - 1857
Опубликована: Апрель 19, 2024
Bromodomain
4
and
9
(BRD4
BRD9)
have
been
regarded
as
important
targets
of
drug
designs
in
regard
to
the
treatment
multiple
diseases.
In
our
current
study,
molecular
dynamics
(MD)
simulations,
deep
learning
(DL)
binding
free
energy
calculations
are
integrated
probe
modes
three
inhibitors
(H1B,
JQ1
TVU)
BRD4
BRD9.
The
MD
trajectory-based
DL
successfully
identify
significant
functional
function
domains,
such
BC-loop
ZA-loop.
information
from
post-processing
analysis
simulations
indicates
that
inhibitor
highly
influences
structural
flexibility
dynamic
behavior
results
MM-GBSA
not
only
suggest
ability
H1B,
TVU
BRD9
stronger
than
BRD4,
but
they
also
verify
van
der
Walls
interactions
primary
forces
responsible
for
binding.
hot
spots
revealed
by
residue-based
estimation
provide
target
sites
design
This
work
is
anticipated
useful
theoretical
aids
development
selective
over
BRD
family
members.
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.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(9), С. 4699 - 4699
Опубликована: Апрель 25, 2024
In
the
age
of
information
technology
and
additional
computational
search
tools
software
available,
this
systematic
review
aimed
to
identify
potential
therapeutic
targets
for
obesity,
evaluated
in
silico
subsequently
validated
vivo.
The
was
initially
guided
by
research
question
“What
have
been
used
analysis
treatment
obesity?”
structured
based
on
acronym
PECo
(P,
problem;
E,
exposure;
Co,
context).
protocol
formulated
registered
PROSPERO
(CRD42022353808)
accordance
with
Preferred
Reporting
Items
Checklist
Systematic
Review
Meta-Analysis
Protocols
(PRISMA-P),
PRISMA
followed
review.
studies
were
selected
according
eligibility
criteria,
aligned
PECo,
following
databases:
PubMed,
ScienceDirect,
Scopus,
Web
Science,
BVS,
EMBASE.
strategy
yielded
1142
articles,
from
which,
evaluation
12
included
Only
seven
these
articles
allowed
identification
both
vivo
reassessed
targets.
Among
targets,
five
exclusively
experimental,
one
theoretical,
presented
an
experimental
portion
a
obtained
modeling.
predominant
methodology
molecular
docking
most
studied
target
Human
Pancreatic
Lipase
(HPL)
(n
=
4).
lack
methodological
details
resulted
more
than
50%
papers
being
categorized
“unclear
risk
bias”
across
eight
out
eleven
criteria.
From
current
review,
it
seems
evident
that
integrating
methodologies
into
drug
exploration
new
agents
provides
important
tool,
given
ongoing
challenges
controlling
obesity.
