In
recent
years,
the
emergence
of
cancer
drug
resistance
is
one
crucial
tumor
hallmarks
which
supported
by
level
genetic
heterogeneity
and
complexities
at
cellular
levels.
Oxidative
stress,
immune
evasion,
metabolic
reprogramming,
overexpression
ABC
transporters
stemness
are
among
several
key
contributing
molecular
response
mechanisms.
Topo-active
drugs,
e.g.,
doxorubicin
topotecan,
clinically
active
utilized
extensively
against
a
wide
variety
human
tumors
often
results
in
development
failure
to
therapy.
Thus,
there
an
urgent
need
for
incremental
comprehensive
understanding
mechanisms
specifically
context
topo-active
drugs.
This
review
delves
into
intricate
mechanistic
aspects
these
intracellular
extracellular
explores
use
potential
combinatorial
approaches
utilizing
various
drugs
inhibitors
pathways
involved
resistance.
We
believe
that
this
will
help
guide
basic
scientists,
pre-clinicians,
clinicians,
policymakers
toward
holistic
interdisciplinary
strategies
transcend
resistance,
renewing
optimism
ongoing
battle
cancer.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(4), P. 680 - 680
Published: Feb. 6, 2024
In
recent
years,
the
emergence
of
cancer
drug
resistance
has
been
one
crucial
tumor
hallmarks
that
are
supported
by
level
genetic
heterogeneity
and
complexities
at
cellular
levels.
Oxidative
stress,
immune
evasion,
metabolic
reprogramming,
overexpression
ABC
transporters,
stemness
among
several
key
contributing
molecular
response
mechanisms.
Topo-active
drugs,
e.g.,
doxorubicin
topotecan,
clinically
active
utilized
extensively
against
a
wide
variety
human
tumors
often
result
in
development
failure
to
therapy.
Thus,
there
is
an
urgent
need
for
incremental
comprehensive
understanding
mechanisms
specifically
context
topo-active
drugs.
This
review
delves
into
intricate
mechanistic
aspects
these
intracellular
extracellular
explores
use
potential
combinatorial
approaches
utilizing
various
drugs
inhibitors
pathways
involved
resistance.
We
believe
this
will
help
guide
basic
scientists,
pre-clinicians,
clinicians,
policymakers
toward
holistic
interdisciplinary
strategies
transcend
resistance,
renewing
optimism
ongoing
battle
cancer.
RSC Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
15(3), P. 981 - 997
Published: Jan. 1, 2024
Novel
chloropyridazine
hybrids
as
promising
anticancer
agents
acting
by
apoptosis
induction
and
PARP-1
inhibition
through
a
molecular
hybridization
strategy.
RSC Advances,
Journal Year:
2025,
Volume and Issue:
15(6), P. 4593 - 4606
Published: Jan. 1, 2025
Various
α-cyano
bis(indolyl)chalcones
synthesized
in
excellent
yields
(up
to
95%)
were
found
display
good
cytotoxicity
(IC
50
=
0.9–5.8
μM)
and
caused
apoptosis
C4-2
cells.
Drug Development Research,
Journal Year:
2025,
Volume and Issue:
86(2)
Published: March 18, 2025
ABSTRACT
Herein,
we
report
the
design,
synthesis,
and
characterization
of
novel
organoselenium
(OSe)
hybrids
(
5
–
19
)
via
modifications
lead,
N
‐(4‐selaneylphenyl)‐2‐selaneylacetamide.
The
OSe‐based
thiazol
9
showed
highest
growth
inhibition
%
(GI%)
64.72%
relative
to
positive
reference
doxorubicin
(DOX),
with
a
GI%
79.5%.
Furthermore,
OSe
derivatives
low
values
compared
normal
cell
lines
employed,
demonstrating
their
selectivity.
tethered
‐chloroacetamide
Schiff
base
cytotoxic
effect
an
IC
50
(25.07
11.61
µM),
respectively,
against
A549
tumor
line
(34.22
20.12
HELA
cancer
line.
Enzyme‐linked
immunosorbent
assay
study
JAK1
STAT3
inhibitory
potentials
compounds
in
cells
both
promising
activities
25.07
µM,
respectively.
Protein
expression
analysis
on
upregulation
P53,
BAX,
Caspases
3,
6,
8,
as
apoptotic
proteins.
However,
candidates
expressed
downregulation
antiapoptotic
proteins
(BCL2,
MMP2,
MMP9).
Moreover,
described
examined
inflammatory
proteins:
COX2,
IL‐6,
IL‐1β.
In
addition,
compound
potential
cycle
arrest
at
G0,
S,
G2‐M
layers,
increase
cellular
levels.
Finally,
molecular
docking
studies
most
toward
target
receptors,
binding
scores
interactions
exceeding
that
cocrystallized
inhibitor
JAK1.
Future Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
16(2), P. 105 - 123
Published: Jan. 1, 2024
Aim:
A
novel
series
of
fused
benzochromenes
with
expected
cytotoxicity
and
HIF-1α
inhibition
was
identified.
Materials
&
methods:
bioisosterism-aided
approach
applied
to
design
new
assess
their
against
three
cancer
cell
lines.
The
probable
mechanistic
effect
the
in
silico
docking
pharmacokinetic
profiles
most
effective
derivatives
were
evaluated.
Results:
Compounds
3,
4,
5,
8
11
showed
potent
antiproliferative
activity
excellent
selectivity.
Compound
significant
an
IC50
value
3.372
μM.
It
also
enhanced
apoptosis
arrested
HepG2
cycle
at
both
G0/G1
S
stages.
Conclusion:
identified
as
a
potential
anticancer
candidate.
Future Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
15(19), P. 1773 - 1790
Published: Oct. 1, 2023
Aim:
Our
objective
was
to
design
and
synthesize
a
new
range
of
pyrazolopyrimidines
while
maintaining
the
key
pharmacophoric
features
EGFR
tyrosine
kinase
inhibitors.
Materials
&
methods:
Percentage
inhibition
in
14
human
cancer
cell
lines
IC50
values
were
recorded.
Compounds
6c,
7e
7f
examined
against
both
wild
mutant
(T790M)
subtypes.
Apoptosis
markers,
cycle
arrest,
apoptosis
assay
molecular
docking
performed.
Results:
demonstrated
superior
inhibitory
potentials
A
study
showed
that
compounds
6c
had
best
fit.
Conclusion:
The
designed
candidates
potential
as
promising
EGFR-T790M
inhibitors
agrees
with
proposed
rationale.
