Abstract
A
series
of
novel
2‐(chloromethyl)‐5‐(3,
5‐disubstituted‐1
H
‐indol‐2‐yl)‐1,3,4‐oxadiazole
(
3
a
–
h
)
derivatives
have
been
synthesized
as
potential
COX
inhibitors,
anti‐TB,
and
anti‐oxidant
activities.
The
structures
were
confirmed
by
IR,
NMR
1
13
C)
mass
spectral
techniques.
physicochemical
properties,
ADME,
drug‐likeness
profile
for
the
compounds
evaluated
SwissADME.
Based
on
our
interest
in
indole
chemistry
SAR
study,
foresaid
examined
vitro
inhibitory
activity,
antioxidant
ADME
studies
disclosed
newly
compounds.
,
b
c
recognized
outstanding
COX‐II
inhibitions
with
IC
50
values
0.28,
0.24,
0.45
μM
compared
to
standard
drugs.
,and
showed
anti‐TB
activity
MIC
value
0.78
μg/mL.
attested
at
10
μg/ml
rate
inhibition
66.52
%,
68.25
65.95
%
respectively.
Finally,
molecular
docking
carried
out
cyclooxygenase‐2
PDB
ID:
6COX
),
M.
tuberculosis
enoyl
reductase
(INHA)
complexed
1‐cyclohexyl‐
N
‐(3,5‐dichlorophenyl)‐5‐oxopyrrolidine‐3‐carboxamide
4TZK
cytochrome
peroxidase
2X08
all
derivatives.
selected
taken
their
dynamic
studies.
Natural Product Research,
Год журнала:
2024,
Номер
unknown, С. 1 - 8
Опубликована: Янв. 11, 2024
This
study
investigates
the
anti-cancer
potential
of
recently
discovered
indole
alkaloids
from
Nauclea
Officinalis
against
third
and
fourth-generation
EGFR
mutations
using
computational
tools.
Through
ADMET
profiling,
druglikeness
prediction,
docking,
simulations,
we
assessed
their
pharmacokinetics,
binding
interactions,
stability.
Promising
affinity
were
observed,
particularly
for
(±)-19-O-butylangustoline,
which
demonstrated
stronger
both
mutants.
MD
simulations
confirmed
stable
with
(±)-19-O-butylangustoline
exhibiting
highest
These
findings
highlight
these
as
agents,
warranting
further
optimisation
therapeutic
development.
informs
through
insights
into
molecular
properties
energetics.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
42(4), С. 1751 - 1764
Опубликована: Апрель 27, 2023
Pyrimidine
and
its
derivatives
are
associated
with
varieties
of
biological
properties.
Therefore,
we
herein
reported
the
synthesis
four
novel
pyrimidines
(2,
3,
4a,
b)
derivatives.
The
structure
these
molecules
is
confirmed
by
spectroscopic
methods
such
as
IR,
NMR,
Mass
analysis.
electronic
behavior
synthesized
compounds
b
in
silico
drug
design
4
c,
d
was
explained
Density
Functional
Theory
estimations
at
DFT/B3LYP
level
via
6-31
G++
(d,
p)
replicates
geometry.
All
were
screened
for
their
vitro
COX-1
COX-2
inhibitory
activity
compared
to
standards
Celecoxib
Ibuprofen.
Compounds
3
4a
afforded
excellent
activities
IC50
=
5.50
5.05
μM
against
COX-1,
0.85
0.65
COX-2,
respectively.
standard
drugs
Ibuprofen
showed
6.34
3.1
0.56
1.2
Further,
high
potential
docking
SARS-CoV-2
Omicron
protease
&
predicted
drug-likeness
pyrimidine
analogs
using
Molinspiration.
protein
stability,
fluctuations
APO–protein,
protein–ligand
complexes
investigated
through
Molecular
Dynamics
simulations
studies
Desmond
Maestro
11.3
lead
identified.Communicated
Ramaswamy
H.
Sarma
Polycyclic aromatic compounds,
Год журнала:
2023,
Номер
44(1), С. 473 - 487
Опубликована: Фев. 15, 2023
We
report
derivatives
of
2,5-disubstituted-1,3,4-oxadiazole
as
powerful
anti-TB
and
antioxidant
compounds.
Using
substituted
aryloxy
acetic
acids
(2a–f)
isoniazid
(3)
in
the
presence
phosphorus
oxychloride,
a
series
new
2-(substituted-aryloxymethyl)-5-(pyridin-4-yl)-1,3,4-oxadiazoles
(4a–f)
are
synthesized.
IR,
1H
NMR,
mass
spectral
data
were
used
to
physically
spectroscopically
describe
synthesized
molecules.
Density
Functional
Theory
(DFT)
calculations
performed
at
DFT/B3LYP
level
using
6-31
G++
(d,
p)
reproduce
structure
geometry.
The
non-linear
visual
characteristic
compounds
is
determined
by
first-order
hyperpolarizability
calculation.
To
analyze
charge
transfer
interface
between
structures,
HOMO
LUMO
investigations
used.
vitro
activity
was
carried
out.
compound
4d
exhibited
excellent
with
MIC
value
3.12
µg/ml.
4b
4c
showed
promising
concentration
10
µg/ml
inhibition
rates
68.36%
69.26%
respectively.
Furthermore,
docking
studies
for
newly
molecules
out
Auto
dock
software
proteins
InhA
(4TZK)
Cytochrome
c
peroxidase
(2X08).
All
strong
binding
affinity
docked
proteins.
Abstract
Cancer
is
deemed
to
be
one
of
the
most
severe
diseases,
which
accountable
for
elevated
mortality
rate
after
cardiovascular
diseases.
Despite
huge
numbers
drugs
that
were
approved
by
USFDA
combat
prevalence
cancer,
resistance
diverse
cancer
types
current
medications
as
well
their
high
toxicity
becomes
an
obstacle
in
therapy.
Thus,
developing
new
with
improved
selectivity
and
efficiency
cure
various
disease
still
imperative
goal.
Kinases
are
phosphorylating
enzymes
catalyze
transfer
phosphate
from
ATP
tyrosine,
serine
threonine
residues
proteins,
leads
activation
varied
signaling
pathways
regulate
cellular
functions
such
differentiation,
proliferation,
migration
angiogenesis.
Abnormal
phosphorylation
diseases
overexpression
kinases
was
frequently
observed
different
cancerous
tissues.
suppression
kinase
activity
has
stood
out
a
strategic
pathway
Otherwise,
indole
core
displayed
privileged
scaffold
promising
anticancer
properties
multi‐kinase
effect.
This
review
presents
indole‐based
agents
inhibitors
recent
decade.
In
addition,
interactions
derivatives
within
active
pocket
have
been
highlighted.
article
comprises
research
reports
2014
until
present.
