Molecules,
Год журнала:
2024,
Номер
29(7), С. 1685 - 1685
Опубликована: Апрель 8, 2024
Two
new
phenylspirodrimanes,
stachybotrins
K
and
L
(1
2),
together
with
eight
known
analogues
(3–10),
were
isolated
from
deep-sea-derived
Stachybotrys
sp.
MCCC
3A00409.
Their
structures
determined
by
extensive
NMR
data
mass
spectroscopic
analysis.
Absolute
configurations
of
compounds
through
a
comparison
their
circular
dichroism
(CD)
spectra
other
reported
compounds.
The
possible
reversal
effects
all
assayed
in
the
resistant
cancer
cell
lines.
Stachybotrysin
B
(8)
can
reverse
multidrug
resistance
(MDR)
ABCB1-overexpression
cells
(KBv200,
Hela/VCR)
at
non-cytotoxic
concentration.
Doxorubicin
accumulation
assay
molecular-docking
analysis
reveal
that
mechanism
its
MDR
effect
may
be
related
to
increase
intracellular
concentration
substrate
anticancer
drugs.
RSC Medicinal Chemistry,
Год журнала:
2024,
Номер
15(5), С. 1675 - 1685
Опубликована: Янв. 1, 2024
Based
on
synthetic
methodology-based
library,
a
new
class
of
tricyclic
spiroindole
derivatives
as
potent
P-glycoprotein
inhibitors
with
excellent
tumor
multidrug
resistance
reversal
activity
was
discovered.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2024,
Номер
39(1)
Опубликована: Авг. 14, 2024
EcGUS
has
drawn
considerable
attention
for
its
role
as
a
target
in
alleviating
serious
GIAEs.
In
this
study,
series
of
72
(thio)urea
derivatives
were
designed,
synthesised,
and
biologically
assayed.
The
bioassay
results
revealed
that
E-9
(IC50
=
2.68
μM)
exhibited
promising
inhibitory
effect
on
EcGUS,
surpassing
inhibitor
D-saccharic
acid-1,4-lactone
(DSL,
IC50
45.8
μM).
Additionally,
the
kinetic
study
indicated
(Ki
1.64
acted
an
uncompetitive
against
EcGUS.
structure-activity
relationship
introducing
electron-withdrawing
group
into
benzene
ring
at
para-position
is
beneficial
enhancing
activity
Furthermore,
molecular
docking
analysis
strong
affinity
to
by
forming
interactions
with
residues
Asp
163,
Tyr
472,
Glu
504.
Overall,
these
suggested
could
be
potent
inhibitor,
providing
valuable
insights
guidelines
development
future
inhibitors
targeting
Marine Drugs,
Год журнала:
2023,
Номер
21(5), С. 314 - 314
Опубликована: Май 20, 2023
Multidrug
resistance
(MDR)
caused
by
ATP-Binding
Cassette
Subfamily
B
Member
1
(ABCB1,
P-glycoprotein,
P-gp)
is
a
major
barrier
for
the
success
of
chemotherapy
in
clinics.
In
this
study,
we
designed
and
synthesized
total
19
Lissodendrins
analogues
tested
their
ABCB1-mediated
MDR
reversal
activity
doxorubicin
(DOX)-resistant
K562/ADR
MCF-7/ADR
cells.
Among
all
derivatives,
compounds
D1,
D2,
D4
with
dimethoxy-substituted
tetrahydroisoquinoline
fragment
possessed
potent
synergistic
effects
DOX
reversed
drug
resistance.
Notably,
most
compound
D1
merits
multiple
activities,
including
low
cytotoxicity,
strongest
effect,
effectively
reversing
(RF
=
1845.76)
cells
207.86)
to
DOX.
As
reference
substance,
allows
additional
mechanistic
studies
on
ABCB1
inhibition.
The
mechanisms
were
mainly
related
increased
intracellular
accumulation
via
inhibiting
efflux
function
rather
than
from
affecting
expression
level
ABCB1.
These
suggest
that
its
derivatives
might
be
potential
agents
acting
as
inhibitors
clinical
therapeutics
provide
insight
into
design
strategy
development
inhibitors.
Molecules,
Год журнала:
2024,
Номер
29(7), С. 1685 - 1685
Опубликована: Апрель 8, 2024
Two
new
phenylspirodrimanes,
stachybotrins
K
and
L
(1
2),
together
with
eight
known
analogues
(3–10),
were
isolated
from
deep-sea-derived
Stachybotrys
sp.
MCCC
3A00409.
Their
structures
determined
by
extensive
NMR
data
mass
spectroscopic
analysis.
Absolute
configurations
of
compounds
through
a
comparison
their
circular
dichroism
(CD)
spectra
other
reported
compounds.
The
possible
reversal
effects
all
assayed
in
the
resistant
cancer
cell
lines.
Stachybotrysin
B
(8)
can
reverse
multidrug
resistance
(MDR)
ABCB1-overexpression
cells
(KBv200,
Hela/VCR)
at
non-cytotoxic
concentration.
Doxorubicin
accumulation
assay
molecular-docking
analysis
reveal
that
mechanism
its
MDR
effect
may
be
related
to
increase
intracellular
concentration
substrate
anticancer
drugs.
