Novel Butenolide Derivatives as Dual-Chitinase Inhibitors to Arrest the Growth and Development of the Asian Corn Borer.

OfChtI and OfChi-h are considered potential targets for the control of Asian corn borer (Ostrinia furnacalis). In this work, the previously reported OfChtI inhibitor 5f was found to show certain inhibitory activity against OfChi-h (Ki = 5.81 µM). Two series of novel butenolide derivatives based on lead compound 5f were designed with the conjugate skeleton, contributing to the π-binding interaction to chitinase, and then synthesized. Compounds 4a-l and 7a-p displayed excellent inhibitory activities against OfChtI and OfChi-h, respectively, at a concentration of 10 µM. Compound 4h was found to be a good dual-Chitinase inhibitor, with Ki values of 1.82 and 2.00 µM against OfChtI and OfChi-h, respectively. The inhibitory mechanism studies by molecular docking suggested that π-π stacking interactions were crucial to the inhibitory activity of novel butenolide derivatives against two different chitinases. A preliminary bioassay indicated that 4h exhibited certain growth inhibition effects against O. furnacalis. Butenolide-like analogues should be further studied as promising novel dual-chitinase inhibitor candidates for the control of O. furnacalis.

Discovery of Rhodanine Inhibitors Targeting Of ChtI Based on the π-Stacking Effect and Aqueous Solubility.

The application of some reported inhibitors against the chitinolytic enzyme Of ChtI was limited due to their unsatisfactory insecticidal activities. Hence, we first performed a synergetic design strategy combining the π-stacking effect with aqueous solubility to find novel rhodanine analogues with inhibitory activities against Of ChtI. Novel rhodanine compounds IAa-f and IBa-f have weak aqueous solubility, but they (IAd: Ki = 4.0 µM; IBd: Ki = 2.2 µM) showed better inhibitory activities against Of ChtI and comparable insecticidal efficiency toward Ostrinia furnacalis compared to the high aqueous solubility compounds IIAa-f and IIBa-f (IIAd: Ki = 21.6 µM; IIBd: Ki = 14.3 µM) without a large conjugate plane. Further optimized compounds IIIAa-j with a conjugate plane as well as a higher aqueous solubility exhibited similar good inhibitory activities against Of ChtI (IIIAe: Ki = 2.4 µM) and better insecticidal potency (IIIAe: mortality rate of 63.33%) compared to compounds IAa-f and IBa-f, respectively. Molecular docking studies indicated that the conjugate planarity with the π-stacking effect for rhodanine analogues is responsible for their enzyme inhibitory activity against Of ChtI. This study provides a new strategy for designing insect chitinolytic enzyme inhibitors as insect growth regulators for pest control.

Discovery of piperonyl-tethered sulfoximines as novel low bee-toxicity aphicides targeting Amelα1/ratß2 complex.

Nicotinic acetylcholine receptor (nAChR) is recognized as a significant insecticide target for neonicotinoids and some agonists. In this study, the nAChR α1 subunit from Apis mellifera was first found to be narrowly tuned to different bee toxicity insecticides, namely, sulfoxaflor (SFX) and flupyradifurone (FPF). Hence, novel sulfoximine derivatives 7a-h were rationally designed and synthesized by introducing a benzo[d][1,3]dioxole moiety into a unique sulfoximine skeleton based on the binding cavity characteristics of Amelα1/ratß2. The two electrode voltage clamp responses of 7a-h were obviously lower than that of SFX, indicating their potentially low bee toxicity. Besides, representative compounds 7b and 7g exhibited low bee toxicity (LD50 > 11.0 µg/bee at 48 h) revealed by acute contact toxicity bioassays. Molecular modelling results indicated that Ile152, Ala151, and Val160 from honeybee subunit Amelα1 and Lys144 and Trp80 from aphid subunit Mpα1 may be crucial for bee toxicity and aphicidal activity, respectively. These results clarify the toxic mechanism of agonist insecticides on nontargeted pollinators and reveal novel scaffold sulfoximine aphicidal candidates with low bee toxicity. These results will provide a new perspective on the rational design and highly effective development of novel eco-friendly insecticides based on the structure of the nAChR subunit.

High value-added application of natural forest product α-pinene: design, synthesis and 3D-QSAR study of novel α-campholenic aldehyde-based 4-methyl-1,2,4-triazole-thioether compounds with significant herbicidal activity.

For exploring novel natural product-derived herbicides, 16 novel α-campholenic aldehyde-based 4-methyl-1,2,4-triazole-thioether compounds were designed, synthesized, and characterized by FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis. The preliminary bioassay showed that, at 100 µg/mL, most of the target compounds displayed significant inhibition activity against root-growth of rape(Brassica campestris L.), with inhibition rates of 85.0%～98.2%(A-class activity level), much better than that of the positive control flumioxazin. In addition, an effective and reasonable 3D-QSAR model was established by CoMFA method in SYBYL-X 2.1.1 software. It was found that, the steric field was the major factor towards the herbicidal activity of the target compounds against B. campestris L., and the introduction of bulky groups into m- and p-position of the benzene ring was favourable to increase the herbicidal activity. This kind of title compounds deserved further study as potential leading compounds for the discovery and development of novel herbicidal agents.

Synthesis of 3-carene-derived nanocellulose/1,3,4-thiadiazole-amide complexes with antifungal activity for plant protection.

BACKGROUND: Nanopesticides have been proved to be a powerful and promising tool to solve the issues in agriculture. The purpose of the present study was to develop ecofriendly nanopesticide systems by the strategy of comprehensive utilization of two natural biomass resources (bagasse and turpentine oil) because of their incomparable advantages. RESULTS: In this research, a series of nanocellulose carriers ETOCN-1-ETOCN-4 (ETOCN, esterified TEMPO-oxidized cellulose nanofibers) with different degrees of substitution were prepared and characterized by Fourier-transform infrared (FTIR), X-ray diffraction (XRD) and transmission electron microscopy (TEM). Then, 21 1,3,4-thiadiazole-amide compounds 8a-8u containing gem-dimethylcyclopropane ring were designed, synthesized and characterized. A preliminary bioassay indicated that compound 8i (R = p-Br Ph) exhibited broad-spectrum antifungal activity against the tested fungi. Furthermore, drug-loading complexes 8i/ETOCN-1-8i/ETOCN-4 were fabricated by integration of nanocellulose-based carriers ETOCN-1-ETOCN-4 with bioactive compound 8i, and the drug-loading capacities, microstructures and sustained-releasing performance of these complexes were also investigated. According to the observation of scanning electron microscopy (SEM) images of complex 8i/ETOCN-2, the small-molecule drug and the carrier formed a well-distributed and compact complex, which led to the excellent drug-loading capacity and sustained-releasing performance in the ethanol/water (1:1, v/v) system. CONCLUSIONS: Complexes 8i/ETOCN-1-8i/ETOCN-4 deserved further study as the promising candidates for the development of nanopesticides. © 2022 Society of Chemical Industry.