Chitinase is one of the most important glycoside hydrolyases, widely existing in bacteria, fungi, insects, and plants. It is involved in fungal cell wall remodeling and insect molting. Chitinase inhibitors are an effective means of controlling pathogens and pests. Natural product argifin is a 17-membered pentapeptide that exhibits efficient chitinase inhibitory activity. However, the complexity of the synthetic process results in a lot of restrictions for wide range of applications. In this work, we designed a series of azamacrolide chitinase inhibitors based on the structural features of argifin that have high inhibitory activities against bacterial and insectile chitinase. The most potent chitinase inhibitor compound 19c exhibited IC 50 values of 56 nM and 110 nM against Of Chi-h and SmChiB, respectively. The molecular docking and molecular dynamics simulations revealed that all inhibitors were bound to the −1 subsite of chitinases via N-methylcarbamoylguanidinyl as well as argifin. Finally, a bioactivity assay against pests was carried out. Compound 18a showed 80% mortality for Mythimna separata at a concentration of 50 mg/L. Besides, insecticides 19b and 19c exhibited high mortality against Plutella xylostella (76 and 73% mortalities at 50 mg/L, respectively).
Chitin
degradation is a vital process for the growth of insects.
Chitin hydrolase OfChtI and β-N-acetylhexosaminidase OfHex1 are two key enzymes
involved in hydrolyzing the chitin of insects’ cuticles. Thus,
they are considered promising targets for preventing and controlling
agricultural pests. In this study, we designed and synthesized a series
of compounds bearing N-methylcarbamoylguanidinyl
and N-methoxycarbonylguanidinyl as dual-target inhibitors
of OfChtI and OfHex1. The most potent
dual-target inhibitor, compound 10d, exhibited half-maximal
inhibitory concentration (IC50) values of 27.1 and 249.1
nM against OfChtI and OfHex1, respectively.
Furthermore, the insecticidal activity studies showed that compounds 10a–c, 10k, and 10l bear significant effects on the growth and development of Plutella xylostella. This work provides a promising
method for the development of novel chitin hydrolase inhibitors as
potential pest control and management agents.
In order to increase the application of natural bioresources
in
drug discovery and development, a study on N-acetyl-glucosamine
(GlcNAc) derivatives of chitin as green pesticides was necessary.
In this study, we designed and synthesized a series of novel C-glycoside naphthalimides using GlcNAc as a starting material.
Compound 10l showed high inhibitory activity against OfHex1 (IC50 = 1.77 μM), with a nearly
30-fold increase in activity over our previously reported C-glycoside CAUZL-A (IC50 = 47.47 μM).
By observing the morphology of the Ostrinia furnacalis, we found that the synthesized compounds significantly inhibited
the molting process. In addition, we further explored the morphological
changes of the inhibitor-treated O. furnacalis cuticle
using scanning electron microscopy. This is the first study to validate
the insecticidal mechanism of OfHex1 inhibitors at
the microscale level. Several compounds also exhibited excellent larvicidal
activity against Plutella xylostella. Moreover, the
toxicity measurements and predictions indicated that the C-glycoside naphthalimides have little effect on the natural enemy Trichogramma ostriniae and rats. Together, our results highlight
an approach for the design of green pesticides, taking advantage of
natural bioresources to control pests in agriculture.
In an effort to develop novel molecules with suitable insecticidal activities, 23,24-alkene-avermectin B2a derivatives have been synthesized via a one-pot multistep reaction using avermectin B2a, a byproduct of avermectin fermentation, as a starting material. All products and intermediates were characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry. Bioassay results showed that the LC 50 values of compounds 4 and 9 against Meloidogyne incognita were 0.63 and 0.50 mg/L, respectively, similar to that of avermectin (0.46 mg/L). Importantly, the LC 50 values of compound 9 against Tetranychus cinnabarinus and Mythimna separate were 0.0067 and 0.047 mg/L, respectively, superior to that of avermectin. Through field experiments, it could be found that spraying 0.25% water-dispersible granules of compound 9 345 g ha −1 could effectively control M. incognita outbreaks, with an efficacy of 84.9%. Combined with toxicity experiments, it could be further inferred that compound 9 may be useful as a lowtoxicity pesticide. In summary, we efficiently synthesized a new B2a derivative as a potential pesticide and offered an important way for improving the utilization efficiency of avermectin fermentation products. In doing so, the environmental pollution associated with fermentation byproducts may be greatly reduced, potentially enabling a sustainable avermectin fermentation process.
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