The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel composed of 5 protein subunits arranged around a central cation selective pore. Several classes of natural and synthetic insecticides mediate their effect through interacting at nAChRs. This review examines the basic pharmacology of the neonicotinoids and related chemistry, with an emphasis on sap-feeding insects from the order Hemiptera, the principle pest target for such insecticides. Although the receptor subunit stoichiometry for endogenous invertebrate nAChRs is unknown, there is clear evidence for the existence of distinct neonicotinoid binding sites in native insect preparations, which reflects the predicted wide repertoire of nAChRs and differing pharmacology within this insecticide class. The spinosyns are principally used to control chewing pests such as Lepidoptera, whilst nereistoxin analogues are used on pests of rice and vegetables through contact and systemic action, the pharmacology of both these insecticides is unique and different to that of the neonicotinoids.
Substituted phenylhydrazone moieties and two carbonate groups were merged in one molecule scaffold to obtain 48 novel compounds. 1H and 13C NMR, MS, elemental analysis, and X-ray single-crystal diffraction were used to confirm their structures. Bioassay results revealed that some of the compounds have strong antifungal activities against Botrytis cinerea, Rhizoctonia solani, and Colletotrichum capsici (especially Rhizoctonia solani). Compound 5H1 is the most promising of the tested compounds against R. solani with an EC50 value of 1.91 mg/L, which is comparable with the positive control fungicide drazoxolon (1.94 mg/L). The structure–activity relationships against R. solani formed three rules: 1) small carbonate groups may improve the antifungal activity of the title compounds; 2) electron-withdrawing groups at the phenyl ring of phenylhydrazone are preferable to their non-substituted counterparts; and 3) halogen at the para position is more beneficial than at the ortho or meta position.
We examined the susceptibility of field strains (BO-1, BO-2, TO-1, and YH-1) and one laboratory strain (H-1) of the western flower thrip, Frankliniella occidentalis, to benzoylureas. LC50 values of novaluron were determined as 0.64 ppm against laboratory strain and 2.1–130 ppm against field strains. In the presence of piperonyl butoxide, a cytochrome P450 inhibitor, the insecticidal activity of novaluron tended to be enhanced. To examine whether point mutations in chitin synthase 1 (CHS1) discovered in an etoxazole-resistant strain of Tetranychus urticae and a benzoylurea-resistant strain of Plutella xylostella exist in F. occidentalis, the nucleotide sequence of CHS1 was analyzed. We found a nonsynonymous substitution that corresponded to the location of the mutations found in T. urticae and P. xylostella in the field strains of F. occidentalis but not in the laboratory strain, indicating that this point mutation might be associated with the benzoylurea resistance exhibited by the field strains.
A field-collected Aphis gossypii clone [Kushima resistant (KR) clone] was resistant to neonicotinoid insecticides (23.8- to 394-fold). RNA-seq and next-generation sequence analyses were conducted to identify nine cytochrome P450 (CYP) genes that were significantly upregulated in the KR clone as compared with those in the insecticide-susceptible clone. A. gossypii P450s were transiently and efficiently expressed in S2 cell to show that CYP6CY22 (c21228) and CYP6CY13 (c21368), which were the most upregulated of the nine P450s in the KR clone, did not degrade sulfoxaflor, a new class of insecticides acting on insect nAChRs, but markedly metabolized all of the neonicotinoids tested. Hence, P450s are likely to underpin neonicotinoid resistance in other aphids as well in the future, and the P450 expression protocol established here will prompt studies on P450-medidated insecticide resistance and structural analyses of relevant metabolites.
Fourteen compounds screened from 5 million compounds in silico were submitted to bioassay to find brassinolide (BL) agonists/antagonists against Arabidopsis thaliana. Of these, two N-benzoyl-N′-phenylpiperazine (NBNPP)-type compounds showed antagonistic activity; however, none showed agonistic activity against A. thaliana. The substituents at the benzoyl moiety of NBNPP were changed to OH groups to derive N-(3,4-dihydroxybenzoyl)-N′-(4-butanoyl-2-fluorophenyl)pyrazine, which was named NSBR1. NSBR1 was rationally designed based on docking simulations and molecular dynamics. NSBR1 significantly suppressed the gene expression of CPD and BR6-ox2, which are known as marker genes for the action of BL. This novel NSBR1 was also effective in the rice lamina inclination assay (RLIA), and the activity in terms of the 50% effective dose (ED50) was determined as 0.79 nmol/plant from the dose–response curve for RLIA.
A water dispersible granule (WDG) was prepared through direct granulation of an agrochemical suspension composed of a mixture of sodium lignosulphonate and polyvinyl alcohol (PVA) as a binder using a fluidized bed granulator. The evaluation of various physicochemical properties showed that the mass median diameter (MMD) and disintegration time of the WDG increased with an increase in the PVA content. It was also revealed that the MMD was positively correlated with the viscosity of the agrochemical suspension and that the disintegration time decreased with an increase in solubility of the binder mixture.
This study examined the seasonal proportion change of ryanodine receptor mutation (G4946E) for Plutella xylostella populations using quantitative sequencing. Results showed that the proportions of G4946E generally increased from spring through summer, but then decreased in autumn. Furthermore, the proportions in late autumn were similar to those in early spring of the subsequent year. These results suggest that diamide effectiveness for P. xylostella control in the reference year can be evaluated based on a proportion survey in the prior year.
The effect of inclusion or exclusion of the root-shoot junction on the estimation of pesticide residue levels in turnip roots and leaves was investigated. Turnips grown at two experimental sites were sprayed with six pesticides. At residue analysis, the turnips were divided in three segments: roots (R), leaves (L), and root-shoot junctions (J). The highest pesticide residue amounts were found in leaves ≥93% of total, with minimal amounts in roots. Residue amounts in root-shoot junctions were intermediate between those of leaves and roots. Residue levels were calculated for the root plus root-shoot junction, and were higher than those in roots: (R+J)/R=1.0–9.0. In contrast, residue levels in the leaf plus root-shoot junction were lower than in leaves only: (L+J)/L=0.76–0.91. The results indicate that the position of the cut between root and leaves could greatly affect the estimated pesticide residue levels when roots and leaves are analyzed separately.
Species sensitivity distribution (SSD) is a key concept of probabilistic analysis for quantifying ecological risk. I developed a method of probabilistic ecological risk assessment in Japan with a case study of the herbicide simetryn. Then, risk comparison among eleven herbicides was conducted using the developed method. However, one of the most important limitations of SSD application is the lack of sufficient toxicity data for SSD analysis. Thus, an ecotoxicity database was developed for the application of SSD to a wide range of pesticides. After that, I proposed that species batteries of the five species should be the standardized dataset for the SSD analysis of insecticides and herbicides. Finally, I have published a technical guidance document for SSD analysis written in Japanese to promote the application of SSDs in Japan. The remarkable point is that the supplemental Excel-based tool makes it easy to analyze SSDs and conduct ecological risk assessments.
Pyflubumide is a novel carboxanilide acaricide discovered and developed by Nihon Nohyaku Co., Ltd., that exhibits excellent acaricidal activity against Tetranychus and Panonychus species, including strains that have developed resistance to conventional acaricides. Its safety profile against non-target arthropods is suitable for integrated pest management (IPM) programs. Pyflubumide was registered and launched in Japan in 2015 and Korea in 2017. This paper describes pyflubumide’s invention history, synthesis, exploratory synthesis, biological activity, toxicological profile, and mode of action.
Fenpyrazamine is a novel fungicide with an aminopyrazolinone structure developed by Sumitomo Chemical Co., Ltd. Fenpyrazamine has good fungicidal properties, such as high antifungal activity, preventive activity, translaminar activity, inhibition activity in lesion development, and long lasting activity. The target enzyme of fenpyrazamine is 3-keto reductase in the ergosterol biosynthetic pathway. Fenpyrazamine shows high efficacy against gray mold, stem rot, and brown rot in field trials. Formulated products, PROLECTUS® and PIXIO®DF, have been registered since 2012. PROLECTUS® was first launched in Italy in 2012, and PIXIO®DF was launched in Japan in 2014.