Malaysian Journal of Fundamental and Applied Sciences,
Год журнала:
2024,
Номер
20(6), С. 1440 - 1459
Опубликована: Дек. 16, 2024
Glucose-6-phosphate
dehydrogenase
deficiency
(G6PDD)
is
a
major
enzymatic
disease
affecting
human
red
blood
cells
(RBCs),
causing
hemolytic
anemia
due
to
the
diminish
of
nicotinamide
adenine
dinucleotide
phosphate
hydrogen
(NADPH)
synthesis
and
altered
redox
balance
within
erythrocytes.
This
study
sought
correct
defect
in
G6PDChatham
(Ala355Thr)
caused
by
loss
interactions
(hydrogen
bonds
salt
bridges)
docking
AG1
molecule
at
dimer
interface,
thus
restoring
these
lost
interactions.
The
enzyme
conformation
was
then
analyzed
before
after
binding
using
molecular
dynamics
simulation
(MDS).
reasons
behind
severity
acute
(AHA)
were
explained
several
parameters,
such
as
root-mean-square
deviation
(RMSD),
fluctuation
(RMSF),
bonds,
bridges,
radius
gyration
(Rg),
solvent
accessible
surface
area
(SASA),
covariance
matrix
analysis.
Structural
alterations
G6PDChatham,
including
absence
key
region
variant
structure,
can
significantly
impact
protein
stability
function,
subsequently
contributing
severity.
Upon
binding,
missing
resorted
structural
variant.
restoration
improves
restores
G6PD
function.
To
develop
new
activators,
analogues
(SY7,
SY8,
SY9,
SY10)
rationally
developed
substituting
linker
structure
with
other
functional
groups
Avogadro
software.
These
compounds
successfully
synthesized
docked
where
best
affinity
ranged
between
-8.0
-9.1
kcal/mol.
promising
activator,
predicted
be
easily
metabolized
excreted,
making
it
less
likely
cause
toxicity.
Its
high
drug
score,
drug-likeness,
favorable
safety
profile
make
strong
candidate
for
cellular
testing.
toxicity
risk
assessment
supported
overall
increasing
confidence
finding
additional
small-molecule
activators
G6PDD
disorder.
Amidst
effective
treatments,
discovery
hopes
improve
lives
those
AHA
assisting
development
appropriate
pharmaceuticals
G6PDD.
ACS Omega,
Год журнала:
2024,
Номер
9(12), С. 13666 - 13679
Опубликована: Март 12, 2024
The
catalytic
activity
of
chitosan
(Cs)
and
grafted
Cs
led
to
the
preparation
terephthalohydrazide
Schiff's
base
hydrogel
(TCsSB),
which
was
then
investigated
as
an
eco-friendly
biocatalyst
for
synthesizing
novel
thiazole
derivatives.
TCsSB
exhibited
greater
surface
area
higher
thermal
stability
compared
Cs,
making
it
a
promising
biocatalyst.
We
synthesized
two
series
thiazoles
via
reaction
2-(2-oxo-1,2-diphenylethylidene)
hydrazine-1-carbothioamide
with
various
hydrazonoyl
chlorides
2-bromo-1-arylethan-1-ones,
employing
ultrasonic
irradiation
using
catalyst.
A
comparative
study
between
revealed
yields
than
TCsSB.
methodology
offered
advantages
such
mild
conditions,
quick
times,
high
yields.
could
be
reused
multiple
times
without
significant
loss
potency.
chemical
structures
newly
compounds
were
verified
through
IR,
Abstract
In
this
work,
we
reported
the
synthesis
of
a
novel
series
isatin‐incorporated
thiazolyl‐coumarin
derivatives
4(a–h)
by
one‐pot
three‐component
reaction
substituted
isatin,
thiosemicarbazide,
and
3‐(2‐bromoacetyl)
coumarin.
The
structures
coumarin‐thiazole
scaffolds
were
precisely
established
their
IR,
NMR,
HRMS
spectral
data.
UV–Vis
absorption
study
target
molecules
was
investigated
in
six
different
solvents.
Geometrical
optimization,
molecular
electrostatic
potential
regions,
quantum
chemical
parameters
assessed
using
density
functional
theory
(DFT)
to
explore
electronic
properties
derivatives.
synthesized
compounds
screened
for
vitro
antimycobacterial
activity
against
Mycobacterium
tuberculosis
;
all
exhibited
excellent
antitubercular
efficacy
with
MIC
≤
3.25
µg/mL;
among
them,
4c
4f
most
potent
1.56
µg/mL.
Furthermore,
silico
docking
analyses
enoyl‐ACP
reductase
(InhA)
enzyme
conducted;
ligands
demonstrated
favorable
binding
interactions
within
active
site
InhA
enzyme.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(4), С. 532 - 532
Опубликована: Апрель 20, 2024
The
tyrosinase
enzyme
has
a
vital
role
in
the
browning
of
vegetables
and
fruits
biosynthesis
melanin.
In
this
work,
we
synthesized
diverse
library
coumarin–triazole
hybrids,
these
compounds
were
characterized
by
using
suitable
analytical
techniques.
Our
research
work
extends
beyond
synthetic
effort
to
explore
therapeutic
potential
compounds.
We
put
through
meticulous
vitro
screening
against
enzyme,
coumarin
derivatives
evinced
good
IC50
values
range
0.339
±
0.25
µM
14.06
0.92
µM.
compounds,
six
found
be
more
potent
than
standard
ascorbic
acid
(IC50
=
11.5
1.00),
among
them,
17e
17f,
being
most
active,
exhibited
remarkable
anti-tyrosinase
potential,
with
μM
3.148
0.23
μM,
respectively.
Furthermore,
an
silico
modeling
study
was
carried
out
determine
key
interactions
protein
(PDB
ID:
2Y9X)
thus
authenticate
our
experimental
findings.
quantitative
SAR
studies
correlation
between
their
activity.
docking
verified
results,
ligand
showed
interaction
core
residues
tyrosinase.
This
not
only
expands
field
hybrid
synthesis
but
also
provides
valuable
insights
for
development
novel
inhibitors.
Pharmaceutics,
Год журнала:
2023,
Номер
15(12), С. 2673 - 2673
Опубликована: Ноя. 25, 2023
The
increasing
cases
of
drug
resistance
and
high
toxicity
associated
with
the
currently
used
antifungal
agents
are
a
worldwide
public
health
concern.
There
is
an
urgent
need
to
develop
new
drugs
unique
target
mechanisms.
Plant-based
compounds,
such
as
carvacrol,
eugenol,
coumarin,
cinnamaldehyde,
curcumin,
thymol,
etc.,
have
been
explored
for
development
promising
due
their
diverse
biological
activities,
lack
toxicity,
availability.
However,
researchers
around
world
unable
fully
utilize
potential
natural
products
limitations,
poor
bioavailability
aqueous
solubility.
hybrid
molecules
containing
synthetic
approach
overcome
these
limitations
control
microbes'
capability
resistance.
Based
on
advantages
compounds
improve
activity,
there
different
reported
synthesized
compounds.
This
paper
reviews
literature
report
activities
products.
