Biointerface Research in Applied Chemistry,
Journal Year:
2022,
Volume and Issue:
13(4), P. 313 - 313
Published: Sept. 12, 2022
In
this
paper,
using
the
mPW1PW91
functional,
quantum
chemical
calculations
were
used
to
explore
electronic,
spectroscopic
properties
and
bonding
of
an
antimalarial
drug
chromium
arene–quinoline
half
sandwich
complex
in
gas
aqueous
phases.
The
solvent
effects
examined
self-consistent
reaction
field
theory
(SCRF)
based
on
polarizable
continuum
model
(PCM).
Reactivity
parameters
chloroquine
compared.
molecular
these
molecules
related
their
biological
activity.
studied
chloroquine's
octanol-water
partition
coefficient
(log
P)
calculated
correlation
between
hardness
activity
was
illustrated.
temperature
dependence
thermodynamic
investigated.
Cr-C
bonds
illustrated
NBO
QTAIM
analyses.
ACS Omega,
Journal Year:
2024,
Volume and Issue:
9(27), P. 29633 - 29643
Published: June 26, 2024
Protein
kinases
are
involved
in
various
diseases
and
currently
represent
potential
targets
for
drug
discovery.
These
play
major
roles
regulating
the
cellular
machinery
control
growth,
homeostasis,
cell
signaling.
Dysregulation
of
kinase
expression
is
associated
with
disorders
such
as
cancer
neurodegeneration.
Pyruvate
dehydrogenase
3
(PDK3)
implicated
therapeutics
a
target.
In
this
current
study,
molecular
docking
exhibited
strong
binding
affinity
myricetin
to
PDK3.
Further,
100
ns
all-atom
dynamics
(MD)
simulation
study
provided
insights
into
structural
stability
PDK3-myricetin
complex,
revealing
formation
stable
complex
minimal
alterations
upon
ligand
binding.
Additionally,
actual
was
ascertained
by
fluorescence
studies,
showed
appreciable
inhibition
assay
suggested
significant
PDK3
myricetin,
an
excellent
inhibitory
IC
Molecules,
Journal Year:
2022,
Volume and Issue:
27(14), P. 4652 - 4652
Published: July 21, 2022
Microtubule
affinity
regulating
kinase
4
(MARK4)
regulates
the
mechanism
of
microtubules
by
its
ability
to
phosphorylate
microtubule-associated
proteins
(MAP's).
MARK4
is
known
for
major
role
in
tau
phosphorylation
via
phosphorylating
Ser262
residue
KXGS
motif,
which
results
detachment
from
microtubule.
In
lieu
this
vital
pathology,
a
hallmark
Alzheimer's
disease
(AD),
druggable
target
treat
AD
and
other
neurodegenerative
disorders
(NDs).
There
growing
evidence
that
NDs
diabetes
are
connected
with
many
pieces
literature
demonstrating
high
risk
developing
diabetic
patients.
Metformin
(Mtf)
has
been
drug
use
against
type
2
mellitus
(T2DM)
long
time;
however,
recent
studies
have
established
therapeutic
effect
diseases
(NDs),
namely
AD,
Parkinson's
(PD)
amnestic
mild
cognitive
impairment.
study,
we
explored
inhibitory
potential
Mtf,
employing
silico
vitro
approaches.
Molecular
docking
demonstrated
Mtf
binds
significant
-6.9
kcal/mol
forming
interactions
binding
pocket's
critical
residues.
Additionally,
molecular
dynamics
(MD)
simulation
provided
an
atomistic
insight
into
MARK4.
ATPase
assay
presence
shows
it
inhibits
IC50
=
7.05
µM.
The
fluorescence
constant
0.6
×
106
M-1.
present
study
provides
additional
axis
towards
utilization
as
inhibitor
targeting
NDs.
ACS Omega,
Journal Year:
2022,
Volume and Issue:
7(38), P. 34370 - 34377
Published: Sept. 19, 2022
Human
serum
albumin
(HSA),
an
abundant
plasma
protein,
binds
to
various
ligands,
acting
as
a
transporter
for
numerous
endogenous
and
exogenous
substances.
Galantamine
(GAL),
alkaloid,
treats
cognitive
decline
in
mild
moderate
Alzheimer's
disease
other
memory
impairments.
A
vital
step
pharmacological
profiling
involves
the
interaction
of
protein
with
drugs,
this
serves
essential
platform
pharmaceutical
industry
advancements.
This
study
is
carried
out
understand
binding
mechanism
GAL
HSA
using
computational
experimental
approaches.
Molecular
docking
revealed
that
preferentially
occupies
Sudlow's
site
I,
i.e.,
subdomain
IIIA.
The
results
unveiled
does
not
induce
any
conformational
change
hence
compromise
functionality
HSA.
dynamics
simulation
(250
ns)
deciphered
stability
HSA-GAL
complex.
We
performed
fluorescence
isothermal
titration
calorimetry
(ITC)
analyze
actual
suggested
significant
affinity.
ITC
measurements
also
delineated
thermodynamic
parameters
associated
Altogether,
present
deciphers
Frontiers in Pharmacology,
Journal Year:
2023,
Volume and Issue:
14
Published: Sept. 19, 2023
Introduction:
Hyperphosphorylation
of
tau
is
an
important
event
in
Alzheimer’s
disease
(AD)
pathogenesis,
leading
to
the
generation
“neurofibrillary
tangles,”
a
histopathological
hallmark
associated
with
onset
AD
and
related
tauopathies.
Microtubule-affinity
regulating
kinase
4
(MARK4)
evolutionarily
conserved
Ser-Thr
(S/T)
that
phosphorylates
microtubule-associated
proteins,
thus
playing
critical
role
pathology.
The
uncontrolled
neuronal
migration
attributed
overexpressed
MARK4,
disruption
microtubule
dynamics.
Inhibiting
MARK4
attractive
strategy
therapeutics.
Methods:
Molecular
docking
was
performed
see
interactions
between
galantamine
(GLT).
Furthermore,
250
ns
molecular
dynamic
studies
were
investigate
stability
conformational
dynamics
MARK4–GLT
complex.
We
fluorescence
binding
isothermal
titration
calorimetry
measure
affinity
GLT
MARK4.
Finally,
enzyme
inhibition
assay
activity
presence
absence
GLT.
Results:
showed
GLT,
acetylcholinesterase
inhibitor,
binds
active
site
cavity
appreciable
affinity.
simulation
for
demonstrated
Fluorescence
suggested
strong
further
show
inhibits
significantly
(IC
50
=
5.87
µM).
Conclusion:
These
results
suggest
potential
inhibitor
could
be
promising
therapeutic
target
AD.
GLT’s
provides
newer
insights
into
mechanism
action,
which
already
used
improve
cognition
patients.
