Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(46), С. 17646 - 17657
Опубликована: Ноя. 8, 2023
Diamide
insecticides
have
gained
popularity
due
to
their
high
efficacy
and
low
toxicity
nontarget
organisms.
However,
diamide-associated
resistance
has
emerged
recently,
causing
a
significant
reduction
in
potency,
thereby
hindering
sustainable
agricultural
development.
Here,
we
explored
novel
diamide
insecticide
analogs
and,
using
structure-based
approach,
rationally
designed
synthesized
28
nitrophenyl
substituted
anthranilic
diamides.
Most
of
the
compounds
showed
moderate
good
activity
against
Mythimna
separata,
Plutella
xylostella,
Spodoptera
frugiperda.
Among
them,
Ia
Im
extraordinarily
mode
action
was
verified
on
isolated
neurons.
Additionally,
exhibited
over
10-fold
greater
potency
than
chlorantraniliprole
HEK293
cell
line
stably
expressing
S.
frugiperda
ryanodine
receptors
(SfRyRs)
containing
mutations,
G4891E
I4734M.
The
binding
modes
SfRyRs
were
predicted
silico
molecular
docking
analysis.
Our
derivatives
provide
valuable
insights
for
design
insecticidal
RyR-targeting
effectively
control
both
wild
type
insecticide-resistant
lepidopteran
pests.
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 4, 2024
Chlorantraniliprole
(CHL),
a
favored
agricultural
insecticide,
is
renowned
for
its
high
efficiency
and
broad-spectrum
effectiveness
against
lepidoptera
insects.
However,
the
urgency
new
insecticide
development
underscored
by
intricate
multistep
preparation
process
modest
overall
yields
of
CHL,
along
with
escalating
challenge
insect
resistance.
In
response,
we
have
crafted
CHL
mimics
from
proline
employing
computer-aided
drug
design.
Molecular
docking
analysis
CHL's
interactions
ryanodine
receptor
(RyR)
revealed
that
nitrogen
atom
within
pyrazole
moiety
does
not
engage
in
pivotal
interactions.
Its
removal
may
abolish
bioactivity
entirely
but
could
substantially
simplify
synthetic
process,
thereby
enhancing
economy.
This
revelation
prompted
exclusion
subsequent
formation
pyrrole
ring,
enabling
meticulous
design
pathways
characterized
cost-effective
precursors,
streamlined
synthesis,
avoidance
toxic
reagents,
minimal
instrumentation,
pursuit
innovative
RyR
modulators.
Among
these
modulators,
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 27, 2024
Abstract
A
series
of
innovative
benzo[4,5]imidazo[1,2‐
b
]pyrazole
scaffold
containing
compounds
were
rationally
designed
through
a
ring‐closure
hopping
strategy
and
synthetized
with
an
intermediate
derivatization
approach.
Physicochemical
properties
analysis
indicated
the
potential
pesticide‐likeness
target
compounds.
The
optimal
compound
A14
showed
relatively
good
insecticidal
activity
against
P.
xylostella
,
LC
50
value
37.58
mg/L,
demonstrated
lower
acute
fish
toxicity
compared
to
fipronil.
Docking
binding
mode
that
bound
GABAR
H‐bond
between
amide
group
residue
6’Thr.
differences
in
modes
fipronil
may
be
key
factor
for
reduced
activities.
elucidated
SAR
profile
lay
foundation
further
structural
optimization
derivatives.
Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(46), С. 17646 - 17657
Опубликована: Ноя. 8, 2023
Diamide
insecticides
have
gained
popularity
due
to
their
high
efficacy
and
low
toxicity
nontarget
organisms.
However,
diamide-associated
resistance
has
emerged
recently,
causing
a
significant
reduction
in
potency,
thereby
hindering
sustainable
agricultural
development.
Here,
we
explored
novel
diamide
insecticide
analogs
and,
using
structure-based
approach,
rationally
designed
synthesized
28
nitrophenyl
substituted
anthranilic
diamides.
Most
of
the
compounds
showed
moderate
good
activity
against
Mythimna
separata,
Plutella
xylostella,
Spodoptera
frugiperda.
Among
them,
Ia
Im
extraordinarily
mode
action
was
verified
on
isolated
neurons.
Additionally,
exhibited
over
10-fold
greater
potency
than
chlorantraniliprole
HEK293
cell
line
stably
expressing
S.
frugiperda
ryanodine
receptors
(SfRyRs)
containing
mutations,
G4891E
I4734M.
The
binding
modes
SfRyRs
were
predicted
silico
molecular
docking
analysis.
Our
derivatives
provide
valuable
insights
for
design
insecticidal
RyR-targeting
effectively
control
both
wild
type
insecticide-resistant
lepidopteran
pests.
