Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
72(6), С. 2935 - 2942
Опубликована: Фев. 5, 2024
Sclerotinia
stem
rot
(SSR)
caused
by
the
phytopathogenic
fungus
sclerotiorum
has
led
to
serious
losses
in
yields
of
oilseed
rape
and
other
crops
every
year.
Here,
we
designed
synthesized
a
series
carboxamide
derivatives
containing
diphenyl
ether
skeleton
adopting
scaffold
splicing
strategy.
From
results
mycelium
growth
inhibition
experiment,
rates
compounds
4j
4i
showed
more
than
80%
control
S.
at
dose
50
μg/mL,
which
is
close
that
positive
(flubeneteram,
95%).
Then,
structure–activity
relationship
study
benzyl
was
very
important
for
antifungal
activity
introducing
halogen
atom
on
ring
would
improve
activity.
Furthermore,
an
vitro
test
suggested
these
novel
can
inhibit
succinate
dehydrogenase
(SDH),
binding
mode
with
SDH
basically
similar
flutolanil
derivative.
Morphological
observation
revealed
compound
could
cause
damage
mycelial
morphology
cell
structure
sclerotiorum,
resulting
mycelia.
vivo
assessment
displayed
good
(>97%)
result
concentration
200
mg/L.
Thus,
new
starting
point
discovery
inhibitors
worthy
further
development.
Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(28), С. 10575 - 10589
Опубликована: Июль 10, 2023
The
conformational
restriction
switch
concept
has
been
adopted
as
a
major
tool
for
structural
optimization
of
pharmaceuticals
in
order
to
expand
the
chemical
structure
scope
and
improve
therapeutic
activity
against
specific
proteins.
Several
1-aminocyclobutanecarboxylic
acid
derivatives
produced
this
way
exhibited
satisfactory
antifungal
vitro
compared
with
positive
control
boscalid.
In
tests
revealed
that
compound
A21
had
comparable,
even
higher
Rhizoctonia
solani
(R.s.,
EC50
=
0.03
mg/L)
Botrytis
cinerea
(B.c.,
0.04
than
fluxapyroxad
0.02
mg/L;
B.c.,
0.20
boscalid
0.29
0.42
mg/L).
Furthermore,
A20
was
successfully
screened
good
inhibitory
porcine
SDH,
its
IC50
value
3.73
μM,
which
considerable
potency
(IC50
3.76
μM).
mode
action
determined
using
SEM
membrane
potential
research.
effects
substituent
steric
hindrance,
electrostatic
property,
hydrophobicity,
hydrogen-bond
fields
on
structure–activity
relationships
were
elaborated
by
reliable
models
comparative
molecular
field
analysis
similarity
index
analysis.
density
functional
theory
simulations,
molecule
potential,
docking
also
used
study
probable
binding
target
compounds
flexible
fragments.
results
showed
scaffold
could
be
lead
discovering
new
succinate
dehydrogenase
inhibitors.
Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(47), С. 18292 - 18300
Опубликована: Сен. 22, 2023
Scaffold
hopping
strategy
has
become
one
of
the
most
successful
methods
in
process
molecular
design.
Seeking
to
develop
novel
succinate
dehydrogenase
inhibitors
(SDHIs),
we
employed
a
scaffold
design
compounds
featuring
geminate
dichloralkenes
(gem-dichloralkenes)
fragment.
After
stepwise
modifications,
series
N-cyclopropyl-dichloralkenes-pyrazole-carboxamide
derivatives
was
synthesized.
Among
them,
G28
(IC50
=
26.00
nM)
and
G40
27.00
were
identified
as
best
inhibitory
activity
against
porcine
SDH,
with
IC50
values
reaching
nanomolar
range,
outperforming
lead
compound
pydiflumetofen.
Additionally,
greenhouse
assay
indicated
that
G37
(EC90
0.031
mg/L)
G34
1.67
displayed
extremely
high
activities
wheat
powdery
mildew
(WPM)
cucumber
(CPM),
respectively.
Computational
results
further
revealed
gem-dichloralkene
fragment
fluorine
substituted
pyrazole
form
an
extra
hydrophobic
interaction
dipolar-dipolar
SDH.
In
summary,
our
study
provides
outstanding
fungicidal
properties,
obtained
through
hopping,
holds
great
potential
for
future
research
on
PM
control.
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
Succinate
dehydrogenase
(SDH)
is
a
globally
recognized
critical
target
for
fungicides.
Our
research
mainly
focuses
on
discovering
novel
molecular
skeletons
targeting
SDH.
We
designed
series
of
diphenyl
ether
ester
derivatives
that
exhibit
potential
efficacy
against
Rhizoctonia
solani
by
utilizing
bioisosteric
approach.
These
results
indicate
compounds
with
shorter
linkers
significantly
enhance
the
antifungal
activity.
Furthermore,
an
ester-linked
compound
was
superior
to
its
amide
and
N-(alkoxy)
counterparts.
Specifically,
ba
achieved
remarkable
92%
in
controlling
R.
at
dosage
50
μg/mL
EC50
value
0.44
μg/mL,
thus
outperforming
boscalid
without
negatively
impacting
rice
growth.
Moreover,
caused
significant
damage
mycelium
demonstrated
IC50
1.69
μM
SDH,
exhibiting
comparable
boscalid.
unveil
promising
avenue
replacing
traditional
heterocyclic
amide-based
inhibitors,
potentially
heralding
new
generation
SDH-targeting
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 3, 2025
Scaffold
optimization
plays
a
critical
role
in
the
exploration
of
fungicides
with
improved
potency
and
an
expanded
spectrum.
In
this
study,
series
novel
pyrazole
β-ketonitrile
derivatives
were
rationally
designed
identified
as
potent
broad-spectrum
succinate
dehydrogenase
inhibitor
fungicides,
through
modifying
molecular
flexibility
via
flexible
methylene
motif.
After
stepwise
modifications,
compounds
A21,
A24,
A33
displayed
broad
spectrum
antifungal
activities
vitro
against
Fusarium
graminearum,
Sclerotinia
sclerotiorum,
Rhizoctonia
solani.
Especially,
compound
(EC50
=
0.356
μg/mL)
exhibited
comparable
fungicidal
F.
graminearum
to
positive
control
pydiflumetofen
0.104
μg/mL).
greenhouse
assay,
moderate
vivo
protective
effects
rice
blast
at
100
μg/mL,
significant
protection
cucumber
powdery
mildew
50
wheat
scab
200
μg/mL.
The
(SDH)
inhibitory
assay
revealed
that
are
SDH
inhibitors
concentration
values
0.123,
0.0317,
0.0709
μM,
respectively.
Docking
results
demonstrated
H-bonds
cation-π
interactions
between
residues
Trp173,
Tyr91,
Arg46
important
for
binding
within
SDH.
Our
findings
improvement
scaffold
is
effective
approach
explore
SDHIs.
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
72(47), С. 26027 - 26039
Опубликована: Ноя. 14, 2024
Succinate
dehydrogenase
inhibitors
(SDHIs)
have
become
one
of
the
most
important
classes
agrochemical
fungicides.
According
to
data
from
FRAC,
resistance
risk
for
SDHIs
had
reached
up
medium
and
even
high.
In
general,
chemical
structure
mainly
contained
three
fragments:
an
acid
core,
a
hydrophobic
tail,
amide
linker,
corresponding
modification
directions
each
fragment.
Among
them,
linker
(ALM)
has
research
hotspot
design
novel
fungicides
in
recent
years.
We
presented
here
detailed
review
on
ALM
strategy
past
decade,
some
them
entered
market.
their
structures,
were
classified
into
four
parts:
(1)
linked
aliphatic
chain
between
bond
(2)
introducing
substituents
replacing
hydrogen
atom
bond,
(3)
reverse
extending
(4)
changed
with
other
bioisosteres.
Moreover,
structure–activity
relationship
interaction
mechanism
ALM-SDHI
SDH
discussed.
This
aims
provide
global
perspective
development
SDHIs,
as
well
suggestions
food
safety
management.
