Knock-in mutagenesis in Drosophila Rdl underscores the critical role of the conserved M3 glycine in mediating the actions of broflanilide and isocycloseram on GABA receptors.

γ-Aminobutyric acid receptors (GABARs) are crucial targets for pest control chemicals, including meta-diamide and isoxazoline insecticides, which act as negative allosteric modulators of insect GABARs. Previous cell-based assays have indicated that amino acid residues in the transmembrane cavity between adjacent subunits of Drosophila RDL GABAR (i.e.

Controlled expression of nicotinic acetylcholine receptor-encoding genes in insects uncovers distinct mechanisms of action of the neonicotinoid insecticide dinotefuran.

Dinotefuran, a neonicotinoid, is a unique insecticide owing to its structure and action. We took two approaches that employed insects with controlled expression of nicotinic acetylcholine receptor (nAChR)-encoding genes to gain insight into the uniqueness of dinotefuran. First, we examined the insecticidal activity of dinotefuran and imidacloprid against brown planthoppers (Nilaparvata lugens), in which the expression of eight (of 13) individual subunit-encoding genes was specifically reduced using RNA interference.

Novel fungicide quinofumelin shows selectivity for fungal dihydroorotate dehydrogenase over the corresponding human enzyme.

The species selectivity of class 2 dihydroorotate dehydrogenase (DHODH), a target enzyme for quinofumelin, was examined. The DHODH (HsDHODH) assay system was developed to compare the selectivity of quinofumelin for fungi with that for mammals. The IC values of quinofumelin for DHODH (PoDHODH) and HsDHODH were 2.

Design and biological activity of a novel fungicide, quinofumelin.

Developed by Mitsui Chemicals Agro, Inc. (Tokyo, Japan), quinofumelin is a novel fungicide with a distinct chemical structure including 3-(isoquinolin-1-yl) quinoline, demonstrating fungicidal activity against a variety of fungi, including rice blast and gray mold. We screened our compound library to identify curative compounds for rice blast and evaluated the effect of fungicide-resistant strains of gray mold.

The target site of the novel fungicide quinofumelin, class II dihydroorotate dehydrogenase.

The target site of the novel fungicide quinofumelin was investigated in the rice blast fungus . Quinofumelin-induced mycelial growth inhibition was reversed by orotate but not by dihydroorotate. Recovery tests suggested that the target site of quinofumelin was dihydroorotate dehydrogenase (DHODH), which catalyzes the oxidation of dihydroorotate to orotate.

Application of computational methods in the analysis of pesticide target-site and resistance mechanisms.

-diamide insecticides including broflanilide have a high insecticidal activity by acting on RDL GABA receptors. Both membrane potential assays and docking studies suggest that the target site of -diamides is different from that of conventional noncompetitive inhibitors, such as fipronil. In fact, -diamides are effective against cyclodiene- and fipronil-resistant pests that carry target-site mutations.

Experimental and theoretical investigation of the reaction of a 3-amidothiophene derivative with various carbonyl compounds.

The reactions of a 3-amidothiophene derivative, which is a partial structure of penthiopyrad, with various carbonyl compounds were investigated. Depending on the carbonyl compound that was used as a reactant, different products (alkenes and bis-products) were obtained from the attack of the carbon at the 2-position of the 3-amidothiophene on the carbonyl compounds. Density functional theory (DFT) calculations revealed that dehydration conditions were important for the first carbonyl addition to shift the reaction toward the product, as the products are more unstable than reactants other than aldehyde.

Synthesis and fungicidal activities of positional isomers of the -thienylcarboxamide.

To investigate the effects of bioisosteric replacement of the phenyl group with the thienyl group, -phenylcarboxamide and three regioisomers of -(substituted-thienyl)carboxamide were synthesized. The inhibitory activity on the succinate dehydrogenase prepared from the gray mold as well as the fungicidal activity against were evaluated. Two isomers, -(2-substituted-3-thienyl)carboxamide and -(4-substituted-3-thienyl)carboxamide exhibited the same level of activity as the phenyl derivative, whereas -(3-substituted-2-thienyl)carboxamide exhibited lower activity than the phenyl derivative, suggesting that the 2-substituted-3-thienyl and 4-substituted-3-thienyl groups functioned as bioisosteres of the phenyl group in -phenylcarboxamide, but the other did not.

Important amino acids for function of the insect Rdl GABA receptor.

Background: Insect Rdl GABA receptor is an important insecticide target. To design a novel insecticide, studies on the structures of homologous pentameric ligand-gated ion channels provide information about important amino acids that are necessary for the function of insect Rdl GABA receptors.

Results: L9'A, T12'A, T13'A, T13'S, M15'S, and M15'N mutations in the Drosophila Rdl GABA receptor subunit caused the protein to spontaneously adopt the open state conformation.

Mechanisms underlying the selectivity of meta-diamides between insect resistance to dieldrin (RDL) and human γ-aminobutyric acid (GABA) and glycine receptors.

Background: Meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] show high insecticide activity by acting as antagonists to the insect resistance to dieldrin (RDL) γ-aminobutyric acid (GABA) receptors. In contrast, low-level antagonist activities of meta-diamides have been demonstrated against the human GABA type A receptor (GABA R) α1β2γ2S, mammalian GABA R α1β3γ2S, and the human glycine receptor (GlyR) α1β. Glycine residue 336 in the membrane-spanning region M3 of the Drosophila RDL GABA receptor is essential for its high sensitivity to meta-diamide 7, [3-benzamido-N-(2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)-2-fluorobenzamide].

Insecticides, biologics and nematicides: Updates to IRAC's mode of action classification - a tool for resistance management.

Insecticide resistance has been and continues to be a significant problem for invertebrate pest control. As such, effective insecticide resistance management (IRM) is critical to maintain the efficacy of current and future insecticides. A technical group within CropLife International, the Insecticide Resistance Action Committee (IRAC) was established 35 years ago (1984) as an international association of crop protection companies that today spans the globe.

Differential metabolism of neonicotinoids by brown planthopper, Nilaparvata lugens, CYP6ER1 variants.

Imidacloprid is very effective in controlling Nilaparvata lugens Stål, which severely damages rice plants. Following heavy imidacloprid use, imidacloprid-resistant N. lugens, which showed cross-resistance to other neonicotinoids, appeared.

Further characterization of distinct high-affinity binding sites for dinotefuran in the abdominal nerve cord of the American cockroach Periplaneta americana (Blattodea).

Dinotefuran (DTF) is a systemic neonicotinoid insecticide characterized by a tetrahydrofuran ring. In the present study, we examined the characteristics of DTF binding to native nicotinic acetylcholine receptors (nAChRs) expressed in the American cockroach Periplaneta americana using radioligand-binding methods. The Scatchard analysis, using [H]imidacloprid (IMI), indicated that IMI has a single class of high-affinity binding sites in the P.

In vivo and in vitro evidence for the inhibition of homogentisate solanesyltransferase by cyclopyrimorate.

Background: Cyclopyrimorate is a highly effective bleaching herbicide discovered by Mitsui Chemicals Agro, Inc. The target site was recently reported to be homogentisate solanesyltransferase (HST) in the plastoquinone (PQ) biosynthesis pathway on the basis of the number of intermediates in cyclopyrimorate-treated plants and in vitro HST assays. Here, the target site of cyclopyrimorate was further explored using both in vivo and in vitro experiments.

Differential metabolism of neonicotinoids by CYP6CY3 stably expressed in S2 cells.

The peach-potato aphid, , is a serious crop pest that has developed imidacloprid resistance, mainly through overexpression of CYP6CY3. Here, we established a metabolic assay using S2 cells that stably expressed CYP6CY3. We found that CYP6CY3 showed metabolic activity against imidacloprid, as well as acetamiprid, clothianidin, and thiacloprid, but had no activity against dinotefuran.

Differential metabolism of imidacloprid and dinotefuran by Bemisia tabaci CYP6CM1 variants.

Imidacloprid has been used to control one of most serious pests, Bemisia tabaci. However, B. tabaci has developed imidacloprid resistance mainly by over-expressing CYP6CM1.

Discovery of broflanilide, a novel insecticide.

Broflanilide (), discovered by Mitsui Chemicals Agro, Inc., has a unique chemical structure characterized as a -diamide and exhibits high activity against various pests, including Lepidopteran, Coleopteran, and Thysanopteran pests. Because broflanilide has a novel mode of action, the Insecticide Resistance Action Committee (IRAC) categorized it as a member of a new group: Group 30.

Action mechanism of bleaching herbicide cyclopyrimorate, a novel homogentisate solanesyltransferase inhibitor.

The action mechanism of cyclopyrimorate, a novel herbicide for weed control in rice fields, was investigated. Cyclopyrimorate caused bleaching symptoms in similar to those caused by existing carotenoid biosynthesis inhibitors, mesotrione and norflurazon. However, cyclopyrimorate treatment resulted in significant accumulation of homogentisate and a reduction in the level of plastoquinone.

Synthesis and activities of tolprocarb derivatives against : relationships among the activities for polyketide synthase, melanin biosynthesis, and rice blast.

The target site of tolprocarb has been reported to be polyketide synthase (PKS). Here, we evaluated the activities for PKS and melanin biosynthesis as well as the control efficacy of rice blast using a series of tolprocarb derivatives. A comparison of the inhibitory activities of PKS and melanin biosynthesis revealed a linear relationship ( =0.

Broflanilide: A meta-diamide insecticide with a novel mode of action.

Broflanilide is a meta-diamide [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamide] that exhibits high larvicidal activity against Spodoptera litura. It has been suggested that broflanilide is metabolized to desmethyl-broflanilide and that it acts as a noncompetitive resistant-to-dieldrin (RDL) γ-aminobutyric acid (GABA) receptor antagonist. The binding site of desmethyl-broflanilide was demonstrated to be distinct from that of conventional noncompetitive antagonists such as fipronil.

Minireview: Mode of action of meta-diamide insecticides.

Meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor noncompetitive antagonists showing high insecticidal activity against Spodoptera litura. The mode of action of the meta-diamides was demonstrated to be distinct from that of conventional noncompetitive antagonists (NCAs) such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. It was suggested that meta-diamides act at or near G336 in the M3 region of the Drosophila RDL GABA receptor.

Comparison between the modes of action of novel meta-diamide and macrocyclic lactone insecticides on the RDL GABA receptor.

Macrocyclic lactones, avermectins, and milbemycins are widely used to control arthropods, nematodes, and endo- and ectoparasites in livestock and pets. Their main targets are glutamate-gated chloride channels. Furthermore, macrocyclic lactones reportedly interact with insect RDL γ-aminobutyric acid (GABA) receptors, but their modes of action on insect RDL GABA receptors remain unknown.

Novel 3,3a,5,9b-tetrahydro-2H-furo[3,2-c][2] benzopyran derivatives: synthesis of chiral glycol benzyl ether herbicides.

Novel tricyclic 3,3a,5,9b-tetrahydro-2H-furo[3,2-c][2]benzopyran (TFB) derivatives were synthesized, and their herbicidal activities were elucidated. They were synthesized from D-glucose as a natural chiral source. The formation of the TFB skeleton was achieved by a Friedel-Crafts type intramolecular cyclization of methyl 5-deoxy-2,3-O-dibenzyl-5-C-methyl-D-xylofranosides.