Using
a simple one-pot method, we developed a prochloraz (Pro)
and pH-jump reagent-loaded zeolitic imidazolate framework-8 (PD@ZIF-8)
composite for the smart control of Sclerotinia disease. The pH-jump
reagent can induce the acidic degradation of ZIF-8 using UV light
to realize the controlled release of Pro. Thus, the physical properties
of PD@ZIF-8, such as its release, formulation stability, and adhesion,
were investigated in detail. The results showed that the quantity
of Pro released by PD@ZIF-8 under UV light irradiation (365 nm) was
63.4 ± 3.5%, whereas under dark conditions, it was only 13.7
± 0.8%. In vitro activity indicated that the
EC50 of PD@ZIF-8 under UV light irradiation was 0.122 ±
0.02 μg/mL, which was not significantly different from that
of Pro (0.107 ± 0.01 μg/mL). Pot experiments showed that
the efficacy of PD@ZIF-8 under light irradiation was 51.2 ± 5.7%
for a fungal infection at 14 days post-spraying, whereas the effectiveness
of prochloraz emulsion in water was only 9.3 ± 3.3%. Furthermore,
fluorescence tracking of ZIF-8 and biosafety experiments showed that
ZIF-8 could be absorbed by plant leaves and transported to various
parts of oilseed rape in a short period of time and that PD@ZIF-8
was relatively safe for plants and HepG2 cells. These results highlight
the potential of the composite to provide efficient and smart delivery
of fungicides into plants for protection against diseases and provide
an idea for developing sustainable agriculture.
Succinate dehydrogenase (SDH) has been demonstrated as a promising target for fungicide discovery. Crystal structure data have indicated that the carboxyl "core" of current SDH inhibitors contributed largely to their binding affinity. Thus, identifying novel carboxyl "core" SDH inhibitors would remarkably improve the biological potency of current SDHI fungicides. Herein, we report the discovery and optimization of novel carboxyl scaffold SDH inhibitor via the integration of in silico library design and a highly specific amide feature-based pharmacophore model. To our delight, a promising SDH inhibitor, A16c (IC = 1.07 μM), with a novel pyrazol-benzoic scaffold was identified, which displayed excellent activity against Rhizoctonia solani (EC = 11.0 μM) and improved potency against Sclerotinia sclerotiorum (EC = 5.5 μM) and Phyricularia grisea (EC = 12.0 μM) in comparison with the positive control thifluzamide, with EC values of 0.09, 33.2, and 33.4 μM, respectively. The results showed that our virtual screening strategy could serve as a powerful tool to accelerate the discovery of novel SDH inhibitors.
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