Search Results (4)

Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound D-27 acting simultaneously on EcR and Ostrinia furnacalis chitinase (OfChtI). Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Ostrinia furnacalis larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, 6j, exhibited promising insecticidal activities against P. xylostella and S. frugiperda. Further protein binding assays and molecular docking indicated that 6j could target both EcR and OfChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs. Full article

Tolfenpyrad, a pyrazolamide insecticide, can be effectively used against pests resistant to carbamate and organophosphate insecticides. In this study, a molecular imprinted polymer using tolfenpyrad as a template molecule was synthesized. The type of functional monomer and the ratio of functional monomer to template were predicted by density function theory. Magnetic molecularly imprinted polymers (MMIPs) were synthesized using 2-vinylpyridine as a functional monomer in the presence of ethylene magnetite nanoparticles at a monomer/tolfenpyrad ratio of 7:1. The successful synthesis of MMIPs is confirmed by the results of the characterization analysis by scanning electron microscopy, nitrogen adsorption–desorption isotherms, Fourier transform infrared spectroscopy, X-ray diffractometer, thermogravimetric analyzer, and vibrational sample magnetometers. A pseudo-second-order kinetic model fit the adsorption of tolfenpyrad, and the kinetic data are in good agreement with the Freundlich isothermal model. The adsorption capacity of the polymer to the target analyte was 7.20 mg/g, indicating an excellent selective extraction capability. In addition, the adsorption capacity of the MMIPs is not significantly lost after several reuses. The MMIPs showed great analytical performance in tolfenpyrad-spiked lettuce samples, with acceptable accuracy (intra- and inter-day recoveries of 90.5–98.8%) and precision (intra- and inter-day relative standard deviations of 1.4–5.2%). Full article

Among the most recent proposals regarding the mechanism of action of dipyrone, the modulation of cannabinoid receptors CB₁ and CB₂ appears to be a promising hypothesis. In this context, the present work describes a series of five novel pyrazolamides (7–11) designed as molecular hybrids of dipyrone metabolites and NSAIDs, such as ibuprofen and flurbiprofen. Target compounds were obtained in good overall yields (50–80%) by classical amide coupling between 4-aminoantipyrine and arylacetic or arylpropionic acids, followed in some cases by N-methylation of the amide group. The compounds presented good physicochemical properties in addition to stability to chemical (pH 2 and 7.4) and enzymatic (plasma esterases) hydrolysis and showed medium to high gastrointestinal and BBB permeabilities in the PAMPA assay. When subjected to functional testing on CB₁- or CB₂-transfected cells, compounds demonstrated an inverse agonist profile on CB₂ receptors and the further characterization of compound LASSBio-2265 (11) revealed moderate binding affinity to CB₂ receptor (K_i = 16 µM) with an EC₅₀ = 0.36 µM (E_max = 63%). LASSBio-2265 (11) (at 1, 3, and 10 mg/kg p.o.) was investigated in the formalin test in mice and a remarkable analgesic activity in the late inflammatory phase was observed, suggesting it could be promising for the treatment of pain syndromes associated with chronic inflammatory diseases. Full article

In order to explore more efficient sulfonamides against Botrytis cinereal, 36 novel cyclohexylsulfonamides were synthesized by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDCI) and 1-hydroxybenzotriazole (HOBt) condensation reaction using chesulfamide as a lead compound, introducing thiazole and pyrazole active groups. Their structures were characterized by ¹H-NMR, ¹³C-NMR, mass spectrum (MS), and elemental analysis. Compound III -31 was further confirmed by X-ray single crystal diffraction. The in vitro and in vivo fungicidal activities against B. cinerea were evaluated by three bioassay methods. The results of mycelial growth demonstrated that median effective concentration (EC₅₀) values of nine compounds were close to boscalid (EC₅₀ = 1.72 µg/mL) and procymidone (EC₅₀ = 1.79 µg/mL) against B. cinerea (KZ-9). In the spore germination experiment, it was found that compounds III-19 and III-31 inhibited germination 93.89 and 98.00%, respectively; at 10 µg/mL, they approached boscalid (95.97%). In the tomato pot experiment, the control effects of two compounds (III-21 and III-27) were 89.80 and 87.90%, respectively, at 200 µg/mL which were significantly higher than boscalid (81.99%). The structure–activity relationship (SAR) was also discussed, which provided a valuable idea for developing new fungicides. Full article