Abstract
In
this
study,
we
aimed
to
investigate
the
inhibitory
mechanisms
of
β‐glucuronidase
by
flavonoids
derived
from
Alhagi
graecorum
through
both
experimental
and
computational
approaches.
The
activity
was
assessed
using
an
in
vitro
enzyme
inhibition
assay,
where
myricetin
chrysoeriol
were
identified
as
potent
inhibitors
based
on
their
low
IC
50
values.
Kinetic
studies
conducted
determine
type,
revealing
that
compounds
exhibit
noncompetitive
β‐glucuronidase‐catalyzed
hydrolysis
PNPG.
Molecular
docking
employed
explore
binding
affinities
flavonoids,
showing
formed
highest
number
polar
interactions
with
enzyme.
Additionally,
molecular
dynamics
(MD)
simulations
performed
evaluate
stability
enzyme‐inhibitor
complexes,
demonstrating
consistent
trajectory
behavior
for
compounds,
significant
energy
stabilization.
Interaction
analyses
highlighted
dominant
role
electrostatic
forces
myricetin′s
mechanism,
while
Van
der
Waals
more
prominent
chrysoeriol.
MM/PBSA
method
used
calculate
free
energies,
exhibiting
lowest
Potential
landscape
analysis
further
revealed
adopts
a
closed
conformation
when
bound
these
inhibitors,
limiting
substrate
access.
These
findings
suggest
hold
promise
clinical
applications,
particularly
managing
drug‐induced
enteropathy.
Abstract
Exploring
the
intricate
mechanisms
of
β
‐glucuronidase
inhibition
is
essential
to
advancing
development
novel
therapeutic
agents.
This
study
extensively
evaluated
inhibitory
potential
phenolics
from
Hibiscus
syriacus
against
using
a
combination
in
vitro
and
computational
approaches.
assays
demonstrated
that
chlorogenic
acid
dactylifric
exhibited
significant
activity,
with
low
IC
50
values
1.32
±
0.08
10.02
1.38
µM,
respectively.
Enzyme
kinetics
analyses
revealed
positive
control,
EGCG,
followed
mixed
mechanism,
while
displayed
competitive
inhibition,
as
indicated
by
intersecting
lines
Lineweaver–Burk
plots.
Docking
studies
supported
these
findings,
showing
lowest
binding
affinities,
extensive
polar
interactions,
occupancy
identical
sites
reference
drug.
A
30
ns
molecular
dynamics
simulation
was
performed
explore
interaction
between
isolated
phenolic
compounds
‐glucuronidase.
Evaluation
multiple
MD
parameters
stable
trajectories
substantial
energy
stabilization
their
These
findings
are
consistent
experimental
data,
supporting
inhibitors
RSC Advances,
Год журнала:
2025,
Номер
15(5), С. 3829 - 3848
Опубликована: Янв. 1, 2025
Apigenin-7-O-glucoside,
silibinin,
and
baicalin
are
potent
squalene
epoxidase
inhibitors
with
promising
therapeutic
potential.
Integrative
in
silico
experimental
studies
pave
the
way
for
hypercholesterolemia
antifungal
therapies.
