Journal of Multidisciplinary Applied Natural Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 18, 2025
Plasmonium
falciparum
dihydrofolate
reductase-thymidylate
synthase
(PfDHFR-TS)
is
one
of
the
most
crucial
antimalarial
targets.
Mutations
in
binding
pocket
this
target
lead
to
resistance
antifolate.
The
mutations
influence
amino
acid
residues
at
points
51,
59,
108
and
164
contribute
significantly
malaria
not
being
treated
well.
Priority
should
therefore
be
given
development
antifolate-resistance
drugs.
These
studies
aim
investigate
new
4-benzyloxy-2-trichloromethylquinazoline
derivatives
as
PfDHFR-TS
inhibitors
using
QSAR,
ADME,
drug-likeness,
toxicity,
molecular
docking
studies,
dynamics
simulations.
best
equation
model
from
QSAR
analysis
used
MLR
PLS
statistics
show
that
pIC50
linearly
related
GATS4e,
SpMax
AEA(ed),
Mor28e,
but
inverted
when
compared
ATS6m
ATSC7m.
predictive
ability
was
confirmed
by
internal
external
validation.
In
addition,
Y-randomization
validation
showed
reliable,
robust,
stable,
with
a
cRp2
score
over
0.5.
ADME
drug-likeness
predictions
design
for
molecules
S10,
S23
S64.
Based
on
toxicity
results,
three
are
expected
have
moderate
non-toxic
properties,
starting
then
S10
Molecular
all
high
energies,
9.869,
9.589,
9.565
kcal/mol.
Leu46,
Asp54,
Ser111,
Thr185
play
major
role
ligand-receptor
interaction
quadruple
mutant
PfDHFR-TS.
Furthermore,
an
evaluation
simulations
complexes
S10-3JSU,
S23-3JSU
S64-3JSU
demonstrated
stable
interactions
100
ns.
