Abstract
The
current
research
is
based
on
the
synthesis
of
some
novel
bis
‐Schiff
bases
bearing
barbituric
acid
moiety
followed
by
characterization
through
modern
spectroscopic
techniques
and
their
in
vitro
inhibitory
effects
against
enzymes
α‐glucosidase
α‐amylase
were
subsequently
investigated.
In
series,
four
compounds
8
(IC
50
=
5.62
±
0.18
3.12
0.13
µM),
10
7.13
1.03
8.19
1.11
9
12.81
1.92
12.11
1.32
11
15.07
0.38
16.01
0.28
µM)
attributed
notable
dual
inhibition
better
than
standard
acarbose
drug
16.16
0.15
16.65
0.17
µM).
molecular
docking
study
was
performed
to
explored
binding
affinities
key
interactions
synthesized
with
targeted
proteins
(α‐amylase
α‐glucosidase).
Furthermore,
stability
all
verified
density
functional
theory
(DFT)
method
at
B3LYP/6–311++G(d,p).
For
account
intramolecular
interaction,
DFT‐D3
reduced
gradient
(RDG)
methods
utilized.
addition,
utilising
CAM‐B3LYP
6–311++G(d,p),
TD‐DFT
approach
used
examine
different
reactivity
circumstances.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 15
Опубликована: Фев. 22, 2024
This
research
work
reports
the
synthesis
of
new
derivatives
hydrazone
Schiff
bases
(1–17)
based
on
polyhydroquinoline
nucleus
through
multistep
reactions.
HR-ESIMS,1H-
and
13C-NMR
spectroscopy
were
used
to
structurally
infer
all
synthesized
compounds
lastly
evaluated
for
prolyl
oligopeptidase
inhibitory
activity.
All
prepared
products
displayed
good
excellent
activity
when
compared
with
standard
z-prolyl-prolinal.
Three
3,
15
14
showed
inhibition
IC50
values
3.21
±
0.15
5.67
0.18
µM,
while
remaining
12
significant
Docking
studies
indicated
a
correlation
biochemical
potency
estimated
in
in-vitro
test
14.
The
MD
simulation
results
confirmed
stability
most
potent
inhibitors
at
250
ns
using
parameters
RMSD,
RMSF,
Rg
number
hydrogen
bonds.
RMSD
indicate
protein
backbone
complex
over
time.
RMSF
binding
site
residues
that
contributed
stabilizing
these
regions
protein,
formed
stable
interactions
protein.
Rg.
analysis
assesses
overall
size
compactness
complexes.
maintenance
bonds
suggests
existence
favorable
interactions.
SASA
they
maintained
conformations
without
large-scale
exposure
solvent.
These
ligand–protein
are
could
be
exploited
design
drugs
disease
treatment.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 12
Опубликована: Март 27, 2024
The
increasing
global
incidence
of
non-insulin-dependent
diabetes
mellitus
(NIDDM)
necessitates
innovative
therapeutic
solutions.
This
study
focuses
on
the
design,
synthesis
and
biological
evaluation
Schiff
base
derivatives
from
2-bromo-2-(2-chlorophenyl)
acetic
acid,
particularly
hydrazone
compounds
4a
4b.
Both
in-vitro
in-vivo
assays
demonstrate
these
derivatives'
strong
antidiabetic
anti-hyperlipidemic
properties.
In
a
15-d
experiment,
we
administered
4b
at
doses
2.5
5
mg/kg
body
weight,
which
effectively
improved
symptoms
alloxan-induced
in
mice.
These
included
weight
loss,
increased
water
consumption
high
blood
glucose
levels.
also
normalized
abnormal
levels
total
cholesterol
(TC),
triacylglycerol
(TG)
low-density
lipoprotein
(LDL-C),
while
raising
high-density
(HDLC).
Computational
analysis
showed
that
inhibited
α-glucosidase
enzyme
by
interacting
with
key
catalytic
residues,
specifically
Asp214
Asp349.
computational
results
were
confirmed
through
tests,
where
inhibitory
activity,
IC50
values
0.70
±
0.11
10.29
0.30
µM,
respectively.
more
effective
than
standard
drug,
acarbose,
had
an
value
873.34
1.67
µM.
Mechanistic
studies
further
indicated
competitive
inhibition,
reinforcing
potential
for
NIDDM
treatment.
