4-Vinylbenzodioxinones as a new type of precursor for palladium-catalyzed (4+3) cycloaddition of azomethine imines.

In this paper, benzo-fused cyclic carbonates were designed and synthesized as a new type of precursor of π-allylpalladium zwitterionic intermediates, and were applied in Pd-catalyzed diastereo- and enantioselective (4+3) cycloaddition with C,N-cyclic azomethine imines, leading to various biologically important 1,3,4-benzoxadiazepine derivatives in 43-99% yields with 6 : 1 to >20 : 1 dr and up to 95% ee.

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.

Odorant-Binding Protein 3-Oriented Rational Design and Discovery of Novel Jasmonate Derivatives as Potential Aphid-Repellent Agents.

Odorant-binding protein (OBP) is a potential target for developing insect behavior control agents due to its properties in transporting semiochemicals. In this study, 12 novel jasmonic acid (JA) derivatives were rationally designed and synthesized based on the binding features between Acyrthosiphon pisum OBP3 (ApisOBP3) and compound D1 [(E)-3,7-dimethylocta-2,6-dien-1-yl 2-(3-oxo-2-pentylcyclopentyl)acetate] with a binding affinity (Kd) of 26.79 µM. Most novel JA derivatives displayed better binding affinities than D1 (Kd = 1-26 µM). Among them, compound 6b [(E)-3,7-dimethylocta-2,6-dien-1-yl-2-((Z)-3-((acryloyloxy)imino)-2-pentylcyclopentyl)acetate] is the most promising compound with an excellent Kd of 1.33 µM and a significant repellent activity with repellent rates of 50-60% against A. pisum and Myzus persicae. Both hydrophobic and electrostatic interactions were found to contribute significantly to the binding of 6b to ApisOBP3. This study provides significant guidance for the rational design and efficient identification of novel aphid repellents based on aphid OBPs.

Piperonyl-Tethered Rhodanine Derivatives Potently Inhibit Chitinolytic Enzymes of Ostrinia furnacalis.

Insect pest chitinases are potential target for developing new insect growth regulators. Piperine was found first to inhibit the insect chitinase (OfChi-h) from Ostrinia furnacalis (Asian corn borer) in this work, except for previously reported OfChtI. Novel piperonyl-tethered rhodanine derivatives 7a-j were rationally designed with piperine as lead and synthesized by introducing a unique rhodanine moiety into the piperine scaffold based on the similar binding cavity of OfChtI and OfChi-h. Compared to piperine, compounds 7a-j showed approximately 100- to 400-fold or 110- to 210-fold higher inhibitory capacity against two chitinases, respectively. Molecular mechanism studies indicated that π interactions are crucial for improving inhibitory activity against two chitinases due to the introduction of the conjugated rhodanine ring. Moreover, compounds 7a-c could dramatically inhibit the growth and development of O. furnacalis larvae by in vivo activity evaluation. This study provides novel piperonyl-tethered rhodanine derivatives inhibiting dual chitinases as insect growth regulator candidates.

Reliability analysis of inertial sensors for testing static balance of 4-to-5-year-old preschoolers.

BACKGROUND: Balance ability is important for preschoolers' motor and physical development. Portable accelerometers can provide resolution tests and identification of preschoolers with balance defects. RESEARCH QUESTION: Despite previous studies on the balance measures of accelerometer tests, there is a lack of complete analyses for preschoolers aged 4-5 years. In this study, we aim to verify the reliability of measuring the static balance of preschoolers in this age range based on inertia sensors for the acceleration and angular velocity moduli. METHODS: Thirty children wore an inertial sensor in the 5th lumbar vertebra and completed four tests, i.e., standing on a firm surface and on a foam surface with open and closed eyes. The standard deviation of the acceleration modulus and root mean square of the angular velocity modulus were calculated. The analysis was based on the intraclass correlation coefficient (ICC) to determine the internal consistency and feasibility. RESULTS: The ICC of the acceleration modulus was between 0.597 and 0.683 (P < 0.01), and the test-retest reliability was medium. The ICC of the angular velocity modulus was between 0.683 and 0.812 (P < 0.01, P < 0.001), and the test-retest reliability was medium to good. The standard error of measurement (SEM) of the acceleration modulus was between 0.001591 and 0.007248 (g), and the SEM% was between 21.24% and 34.12%. The angular velocity modulus SEM values ranged from 1.296 to 3.441 (deg/s), and the SEM% ranged from 25.17% to 33.26%. The difference between the two tests was evenly distributed on both sides of the mean value, and the difference between the test results was within the consistency limit. SIGNIFICANCE: Inertial sensors can be used to evaluate the static balance ability of preschoolers aged 4-5 years. Further, the angular velocity modulus is more reliable than the acceleration modulus.