Abstract
Poly(ADP‐ribose)
polymerase‐10
(PARP10)
is
a
critical
enzyme
involved
in
DNA
damage
repair.
Its
function
cellular
repair
mechanisms
has
been
implicated
the
development
of
chemoresistance
and
radioresistance
cancer
cells.
Consequently,
PARP10
inhibition
represents
promising,
albeit
challenging,
therapeutic
target
for
various
types.
This
study
aims
to
discover
new
potential
inhibitors
via
hybrid
silico
approaches.
Initially,
pharmacophore‐based
virtual
screening
was
conducted
on
ZINC
NCI
databases.
The
resulting
compounds
were
subsequently
subjected
molecular
docking
studies
identify
inhibitors.
Subsequently,
classical
dynamics
(MD)
simulations
evaluate
compare
dynamic
behavior
selected
ligand,
veliparib,
OUL35,
selective
inhibitor.
Ultimately,
compound
ZINC20906412
found
as
lead
based
its
score
favorable
interactions
within
active
site.
may
offer
treatment.
Results in Chemistry,
Год журнала:
2024,
Номер
9, С. 101671 - 101671
Опубликована: Июль 1, 2024
We
have
developed
new
thiadiazole-containing
Schiff
base
derivatives
and
examined
their
ability
to
inhibit
α-amylase
α-glucosidase.
Among
the
members
of
series,
analogue
1
showed
excellent
inhibitory
potential
(IC50
=
1.60
±
0.20
2.40
0.10
µM
for
α-glucosidase)
as
compare
standard
Acarbose
5.30
6.10
µM).
Trifluoromethyl
substituted
analogue-1
best
properties
because
hydrogen
bond
formation.
Analogue
3
9
were
also
found
potent
against
target
enzymes.
All
compounds
investigated
antibacterial
antifungal
activity.
1,
exhibited
bacterial
inhibition
42.3
%,
40.1
38.2
36.5
respectively
in
contrast
streptomycin
(44
%).
4
anti-fungal
potency
43.4,
31.9
34.3
compared
terinafine
(50.6675
Scaffolds
(1–12)
analyzed
through
HREI-mass
spectrometry,
13C
NMR,
1H
NMR.
The
functioning
active
interacting
residues
enzymes
was
determined
by
molecular
docking
(MD),
it
that
thiadiazole
bearing
could
be
considered
suitable
anti-diabetic
drugs.
ADMET
DFT
analysis
performed
determine
stability,
drug
electronic
(electrophilic,
nucleophilic,
HOMO,
LUMO)
synthesized
compounds.
Results in Chemistry,
Год журнала:
2024,
Номер
8, С. 101594 - 101594
Опубликована: Июнь 1, 2024
In
this
study,
we
have
synthesized
S-substituted
benzothiazole
derived
thiazole
bearing
bis-Schiff
base
derivatives
(1–19)
and
characterized
via
different
spectroscopic
techniques
including
NMR
HR-EIMS
then
screened
against
α-amylase
α-glycosidase.
All
the
analogues
show
excellent
inhibitory
capability.
Analogues
1
(IC50
=
3.18
±
0.72
µM
2.30
1.80
µM)
4
1.40
0.59
2.10
0.78
were
found
to
be
strongest
among
all
in
contrast
with
standard
drug
acarbose
4.30
0.18
6.45
1.84
for
Some
good
potency
both
enzymes
while
few
moderately
potent.
For
molecules
structure–activity
relationship
was
carried
determine
decrease/increase
due
steric
hindrance,
bulky
nature,
position,
type,
size,
quantity
of
substituent/s
on
phenyl
rings.
Molecular
docking
ADME
analysis
out
signify
binding
interactions
most
potent
active
site
enzymes.
Zeitschrift für Naturforschung C,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 5, 2025
Abstract
In
pursuit
of
effective
thymidine
phosphorylase
inhibitors,
a
series
hybrid
analogs
thiazole-hydrazone
derivatives
(1–15)
were
synthesized
and
evaluated
for
their
enzyme
inhibitory
potential
using
7-deazaxanthine
as
positive
control.
The
goal
was
to
determine
these
derivatives’
effectiveness
in
suppressing
activity,
target
relevant
antitumor
strategies
due
the
enzyme’s
role
angiogenesis
tumor
growth.
Biological
evaluations
indicated
that
all
displayed
significant
moderate
with
IC
50
values
between
3.93
±
0.90
25.75
4.30
µM.
Particularly,
compounds
12,
9,
28
exhibited
superior
potency,
0.90,
4.10
1.10,
4.50
1.10
µM,
respectively,
surpassing
standard
inhibitor
(IC
=
16.8
2.20
µM).
Additionally,
molecular
docking
studies
performed
elucidate
binding
interactions
active
site
phosphorylase.
results
aligned
well
experimental
data,
revealing
favorable
conformations
support
observed
activities,
particularly
most
potent
compounds.
These
findings
underscore
promise
suggesting
targeted
structural
modifications
could
further
enhance
activity.
Further
investigations,
including
vivo
studies,
are
warranted
explore
applications
anticancer
therapies.
This
study
highlights
valuable
understanding
structure–activity
relationship
(SAR)
derivatives,
emphasizing
advancing
inhibition
therapeutic
purposes.
