Design and development of pyrazol‐5‐ylbenzamide derivatives containing chiral oxazoline moiety as fungicides based on molecular docking
Pest Management Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 16, 2025
Development
of
novel
chiral
antifungal
agents
for
effective
control
plant
pathogens
is
urgently
needed.
In
this
study,
a
series
pyrazol-5-yl-benzamide
derivatives
containing
oxazoline
moiety
were
rationally
designed
and
developed
based
on
molecular
docking.
The
in
vitro
assay
results
indicated
that
compounds
(rac)-4h
(R1
=
Et),
(S)-4
h
S-Et)
(R)-4
R-Et)
exhibited
remarkable
activities
against
Valsa
mali
with
median
concentration
(EC50)
values
0.24,
0.06
1.08
mg/L,
respectively.
Preliminary
structure-activity
relationships
(SARs)
revealed
the
modification
substituent
group
at
significantly
affected
target
compounds.
Furthermore,
(S)-4h
(87.5%)
(R)-4h
(84.3%)
vivo
protective
comparable
to
tebuconazole
V.
mali.
Subsequent
docking
analysis,
succinate
dehydrogenase
(SDH)
enzyme
inhibition
assays
dynamic
(MD)
simulations
verified
potential
class
could
be
SDH
helped
explain
large
difference
(R)-4h.
Confocal
laser
scanning
microscopy
(CLSM)
electron
(SEM)
observations
confirmed
these
two
severely
disrupted
mycelial
morphology
Theoretical
calculation
studies
provided
some
insight
into
subsequent
such
derivatives.
Resistance
frequency
showed
treatments
less
likely
produce
resistant
fungal
strains
than
tebuconazole.
Meanwhile,
no
apparent
toxicity
Apis
mellifera
L.
Therefore,
are
candidates
development
fungicides
crop
protection.
©
2025
Society
Chemical
Industry.
Язык: Английский
Design, synthesis, crystal structure, fungicidal activity, and mechanism of action of novel thiazole-based hydrazide derivatives containing the 4-aminoquinazoline moiety
Bioorganic Chemistry,
Год журнала:
2025,
Номер
156, С. 108237 - 108237
Опубликована: Фев. 2, 2025
Язык: Английский
Antifungal activity and biocompatibility assessment with molecular docking and dynamic simulations of new pyrazole derivatives
BMC Biotechnology,
Год журнала:
2025,
Номер
25(1)
Опубликована: Фев. 6, 2025
Abstract
Background
Because
of
their
many
bioactivities,
which
include
psychoanalytic,
antifungal,
antihypertensive,
anti-inflammatory,
and
antiviral
properties,
pyrazoles
derivatives
are
attracting
interest
in
pharmacology
medicine,
the
pressing
need
for
novel
fungicides
is
increased
lessened
by
growing
microbiological
resistance
illnesses
to
recognized
antibiotics.
Objective
The
current
work
validates
results
pyrazole
binding
sites
as
potent
antifungals
investigating
antifungal
agents.
biocompatibility
was
assessed
using
an
HFB4
normal
human
skin
cell
line.
Methods
evaluated
line
findings
were
confirmed
molecular
docking.
investigation
against
4
fungal
pathogens:
Aspergillus
flavus
ATCC
9643,
A.
niger
11414,
Rhizopus
oryzae
96382,
Penicillium
chrysogenum
10106.
Results
Among
20
different
Pyrazole
derivatives,
3b
most
effective
compound
11414
9643
with
IZDs
AIs
32.0
mm
(1.10)
30.0
(1.0),
respectively.
Followed
10b
scored
28
P.
10106,
While
R.
96382
exhibited
all
compounds.
study
found
that
showed
100%
activity
between
1000
500
μg/ml,
50%
at
doses
250
no
action
a
dose
125
μg/ml
studied
pathogenic
strains.
completely
safe
IC
50
obtained.
effectiveness
several
compounds
targets
through
docking
studies.
highlighted
3b,
3g,
3h,
10b,
7
,
12
displayed
strong
energies,
effectively
engaging
active
key
proteins
various
fungi
such
FDC1
uridine
diphosphate
N
-acetylglucosamine
(UDP-GlcNAc)
Adenosine
5′-phosphosulfate
kinase
.
These
interactions
encompassed
diverse
bonding
types,
suggesting
these
compounds’
potential
hinder
enzyme
demonstrate
notable
properties.
Additionally,
computational
ADMET
“Absorption–distribution–metabolism–excretion–toxicity”
analysis
revealed
adherence
Lipinski’s
rules,
indicating
favorable
physicochemical
characteristics.
dynamic
simulations
5’-phosphosulfate
UDP-N-acetylglucosamine
also
demonstrated
formation
stable
complexes
values
Root
Mean
Square
Deviation
(RMSD),
Fluctuation
(RMSF),
Solvent
Accessible
Surface
Area
(SASA),
Radius
Gyration
(Rg).
support
ongoing
therapeutic
development
projects.
Conclusion
agent.
energies
suggest
drug
development.
Язык: Английский
Novel Diphenyl Ether Carbonyl Ester Fragment as a Promising Skeleton Targeting Succinate Dehydrogenase
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
Язык: Английский
Discovery of Benzothiazol-2-ylthiophenylpyrazole-4-carboxamides as Novel Succinate Dehydrogenase Inhibitors
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
72(32), С. 17802 - 17812
Опубликована: Авг. 2, 2024
Succinate
dehydrogenase
(SDH)
has
been
considered
an
ideal
target
for
discovering
fungicides.
To
develop
novel
SDH
inhibitors,
in
this
work,
31
benzothiazol-2-ylthiophenylpyrazole-4-carboxamides
were
designed
and
synthesized
using
active
fragment
exchange
a
link
approach
as
promising
inhibitors.
The
findings
from
the
tests
on
antifungal
activity
indicated
that
most
of
compounds
displayed
remarkable
inhibition
against
fungi
tested.
Compound
Язык: Английский