Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile
Pharmaceutics,
Год журнала:
2023,
Номер
15(12), С. 2728 - 2728
Опубликована: Дек. 4, 2023
Podophyllotoxin
is
a
naturally
occurring
cyclolignan
isolated
from
rhizomes
of
Podophyllum
sp.
In
the
clinic,
it
used
mainly
as
an
antiviral;
however,
its
antitumor
activity
even
more
interesting.
While
podophyllotoxin
possesses
severe
side
effects
that
limit
development
anticancer
agent,
nevertheless,
has
become
good
lead
compound
for
synthesis
derivatives
with
fewer
and
better
selectivity.
Several
examples,
such
etoposide,
highlight
potential
this
natural
product
chemomodulation
in
search
new
agents.
This
review
focuses
on
recent
chemical
modifications
(2017-mid-2023)
skeleton
performed
at
C-ring
(but
also
lactone
D-ring
trimethoxyphenyl
E-ring)
together
their
biological
properties.
Special
emphasis
placed
hybrids
or
conjugates
other
products
(either
primary
secondary
metabolites)
molecules
(heterocycles,
benzoheterocycles,
synthetic
drugs,
moieties)
contribute
to
improved
bioactivity.
fact,
hybridization
been
strategy
design
enhanced
The
way
which
two
components
are
joined
(directly
through
spacers)
was
considered
organization
review.
comprehensive
perspective
presented
aim
guiding
medicinal
chemistry
community
podophyllotoxin-based
drugs
Язык: Английский
Insights into podophyllotoxin lactone features: New cyclolignans as potential dual tubulin‐topoisomerase II inhibitors
Archiv der Pharmazie,
Год журнала:
2024,
Номер
358(1)
Опубликована: Ноя. 12, 2024
Abstract
Chemomodulation
of
natural
cyclolignans
as
podophyllotoxin
has
been
a
successful
approach
to
obtain
semisynthetic
bioactive
derivates.
One
example
this
is
the
FDA‐approved
drug
etoposide
for
solid
and
hematological
tumors.
It
differs
from
antimitotic
activity
product
in
its
mechanism
action,
being
topoisomerase
II
inhibitor
instead
tubulin
antimitotic.
Within
molecular
requirements
these
compounds,
trans‐γ‐lactone
moiety
presented
parent
compound
always
feature
be
explored
chemomodulate
bioactivity.
In
study,
we
have
obtained
different
compounds
that
comply
with
characteristics
antitubulin
antitopoisomerase
combined
single
molecule.
Furthermore,
influence
trans
‐lactone
on
final
activity,
finding
cis
was
also
interesting
terms
The
best
values
cytotoxicity
cell
cycle
inhibition
were
lacking
lactone
ring,
thus
mimicking
podophyllic
aldehyde
functionalization,
selective
derivate.
analogs
cytotoxic
activity.
present
study
illustrates
potential
chemomodulation
products
such
cyclolignan
derivates
discovery
new
antitumor
agents.
Язык: Английский
Cytotoxic Cyclolignans Obtained by the Enlargement of the Cyclolignan Skeleton of Podophyllic Aldehyde, a Selective Podophyllotoxin-Derived Cyclolignan
Molecules,
Год журнала:
2024,
Номер
29(7), С. 1442 - 1442
Опубликована: Март 23, 2024
Podophyllotoxin,
a
cyclolignan
natural
product,
has
been
the
object
of
extensive
chemomodulation
to
obtain
better
chemotherapeutic
agents.
Among
obtained
podophyllotoxin
derivatives,
podophyllic
aldehyde
showed
very
interesting
potency
and
selectivity
against
several
tumoral
cell
lines,
so
it
became
our
lead
compound
for
further
modifications,
as
described
in
this
work,
oriented
toward
enlargement
skeleton.
Thus,
modifications
performed
at
function
included
nucleophilic
addition
reactions
incorporation
carbon
into
five-membered
rings,
such
thiazolidinones
benzo-fused
azoles.
The
synthesized
derivatives
were
evaluated
types
cancer
cells,
although
some
compounds
cytotoxic
nanomolar
range,
most
them
less
potent
selective
than
parent
aldehyde,
with
being
those
having
lactone
ring
podophyllotoxin.
In
silico
ADME
evaluation
predicted
good
druggability
them.
results
indicate
that
γ-lactone
is
important
potency,
while
α,β-unsaturated
necessary
induce
these
cyclolignans.
Язык: Английский
Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(9), С. 4631 - 4631
Опубликована: Апрель 24, 2024
When
new
antitumor
therapy
drugs
are
discovered,
it
is
essential
to
address
target
molecules
from
the
point
of
view
chemical
structure
and
carry
out
efficient
systematic
evaluation.
In
case
natural
products
derived
compounds,
special
importance
investigate
chemomodulation
further
explore
antitumoral
pharmacological
activities.
this
work,
compound
podophyllic
aldehyde,
a
cyclolignan
product
podophyllotoxin,
has
been
evaluated
for
its
viability,
influence
on
cell
cycle,
effects
intracellular
signaling.
We
used
functional
proteomics
characterization
Compared
with
FDA-approved
drug
etoposide
(another
podophyllotoxin
derivative),
we
found
interesting
results
regarding
cytotoxicity
aldehyde.
addition,
were
able
observe
effect
mitotic
arrest
in
treated
cells.
The
use
aldehyde
resulted
increased
solid
tumor
lines,
compared
etoposide,
blocked
cycle
more
successfully
than
etoposide.
High-throughput
analysis
deregulated
proteins
revealed
selective
antimitotic
mechanism
action
HT-29
line,
contrast
other
hematological
lines.
Also,
apoptotic
profile
was
deciphered.
death
activated
independently
profile.
these
targeted
analyses
have
also
shown
significant
response
signaling
kinases,
key
involved
cascades
proliferation
or
metastasis.
Thanks
comprehensive
remarkable
cytotoxic,
antimitotic,
features
discovered
that
will
repurpose
transformations
analysis.
Язык: Английский