Identification of 1,3,4-oxadiazoles as tubulin-targeted anticancer agents: a combined field-based 3D-QSAR, pharmacophore model-based virtual screening, molecular docking, molecular dynamics simulation, and density functional theory calculation approach
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
42(19), С. 10323 - 10341
Опубликована: Сен. 11, 2023
Cancer
is
one
of
the
most
prominent
causes
death
worldwide
and
tubulin
a
crucial
protein
cytoskeleton
that
maintains
essential
cellular
functions
including
cell
division
as
well
signalling,
makes
an
attractive
drug
target
for
cancer
development.
1,3,4-oxadiazoles
disrupt
microtubule
causing
G2-M
phase
cycle
arrest
provide
anti-proliferative
effect.
In
this
study,
field-based
3D-QSAR
models
were
developed
using
62
bioactive
anti-tubulin
1,3,4-oxadiazoles.
The
best
model
characterized
by
PLS
factor
7
was
rigorously
validated
various
statistical
parameters.
Generated
having
high
degree
confidence
showed
favourable
unfavourable
contours
around
1,3,4-oxadiazole
core
assisted
in
defining
proper
spatial
positioning
desired
functional
groups
better
bioactivity.
A
five
featured
pharmacophore
(AAHHR_1)
same
ligand
library
through
enrichment
analysis
(BEDROC160.9
value
=
0.59,
Average
EF
1%
27.05,
AUC
0.74).
Total
30,212
derivatives
obtained
from
PubChem
database
prefiltered
docked
XP
mode
on
binding
cavity
(PDB
code:
1SA0)
which
led
into
identification
11
HITs
docking
scores
between
-7.530
-9.719
kcal/mol
while
reference
compound
Colchicine
exerted
score
-7.046
kcal/mol.
Following
MM-GBSA
ADME
studies,
HIT1
HIT4
emerged
two
promising
hits.
To
verify
their
thermodynamic
stability
at
site,
molecular
dynamic
simulations
carried
out.
Both
further
subjected
to
DFT
determine
HOMO-LUMO
energy
gap
ensuring
biological
feasibility.
Finally,
based
structural
exploration
set
up
lead
Formula
I
advancements
polymerization
inhibitors
anti-cancer
agents.Communicated
Ramaswamy
H.
Sarma.
Язык: Английский
Metal‐Catalyzed Oxidative C−H Bond Functionalization of 1,4‐Benzoxazinones
Asian Journal of Organic Chemistry,
Год журнала:
2024,
Номер
13(5)
Опубликована: Фев. 19, 2024
Abstract
The
present
review
shows
metal‐catalyzed
oxidative
C(sp
3
)‐H/C(sp
2
)‐H
bond
functionalization
of
1,4‐benzoxazinones
by
utilizing
various
substrates
such
as
indoles,
phosphites
or
phosphine
oxides,
malonate
esters,
and
resorcinol,
which
lead
to
the
formation
new
C−C
C−P
bonds.
metal
catalysts
used
for
these
couplings
include
Fe,
Cu,
Ag,
Ru.
This
follows
a
strategy
involving
either
one‐electron
oxidation
process
(OEO),
ball
milling
technique,
photocatalytic
process.
synthesized
products
in
this
method
show
usefulness
natural
products,
materials,
agriculture,
medicinal
chemistry.
Язык: Английский
Design, synthesis, and antiproliferative activity evaluation of novel cyclic secondary amine containing dithiocarbamate derivatives as potent EGFR inhibitors
Journal of Molecular Structure,
Год журнала:
2025,
Номер
unknown, С. 142036 - 142036
Опубликована: Март 1, 2025
Язык: Английский
COPPER(II) COMPLEXES WITH THIOETHER BASED SNS PINCER LIGAND: SYNTHESIS, CHARACTERIZATION AND ANTIPROLIFERATIVE ACTIVITY
Journal of Structural Chemistry,
Год журнала:
2023,
Номер
64(1), С. 157 - 167
Опубликована: Янв. 1, 2023
Язык: Английский
Synthesis, In Silico Docking Study, and Biological Evaluation of S-Alkylated 1,3,4-Oxadiazole Hybrids
Russian Journal of Organic Chemistry,
Год журнала:
2024,
Номер
60(5), С. 927 - 942
Опубликована: Май 1, 2024
Язык: Английский
Recent Progress in the Synthesis of Benzoxazin-4-Ones, Applications in N-Directed Ortho-Functionalizations, and Biological Significance
Molecules,
Год журнала:
2024,
Номер
29(23), С. 5710 - 5710
Опубликована: Дек. 3, 2024
The
development
of
efficient
synthetic
procedures
to
access
fused
N,
O-heterocyclic
skeletons
has
been
a
pivotal
research
topic
in
organic
synthesis
for
several
years.
Owing
the
applications
O-fused
heterocycles
synthesis,
material
sciences,
and
medicinal
chemistry,
significant
efforts
have
dedicated
design
novel
methods
their
construction.
To
this
end,
1,3-benzoxazin-4-ones
are
privileged
candidates
molecules
often
found
natural
products,
agrochemicals,
materials
science
applications.
In
review,
we
aim
summarize
existing
literature
on
from
2010
onwards.
Moreover,
also
identified
as
an
excellent
native
directing
group
ortho-functionalization
via
C-H
activation,
which
is
strenuous
task
requiring
pre-functionalized
substrates.
latter
part
report,
compiled
interesting
examples
Язык: Английский