1-(6-Chloronicotinyl)-2-nitroimino-imidazolidines and Related Compounds as Potential New Insecticides

Moriya, Keiichi; Shibuya, Katsuhiko; Hattori, Yoshikazu; Tsuboi, Sadao; Shiokawa, Kohzoh; Kagabu, Shinzo

doi:10.1271/bbb.56.364

Cited by 126 publications

(66 citation statements)

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“…Experiments were conducted at room temperature (19-25°C). Imidacloprid was synthesized as described previously (Moriya et al, 1992). ACh chloride and atropine sulfate were purchased from Sigma Aldrich Japan (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Role in the Selectivity of Neonicotinoids of Insect-Specific Basic Residues in Loop D of the Nicotinic Acetylcholine Receptor Agonist Binding Site

Shimomura¹,

Yokota²,

Ihara³

et al. 2006

Mol Pharmacol

118

116

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The insecticide imidacloprid and structurally related neonicotinoids act selectively on insect nicotinic acetylcholine receptors (nAChRs). To investigate the mechanism of neonicotinoid selectivity, we have examined the effects of mutations to basic amino acid residues in loop D of the nAChR acetylcholine (ACh) binding site on the interactions with imidacloprid. The receptors investigated are the recombinant chicken ␣4␤2 nAChR and Drosophila melanogaster D␣2/chicken ␤2 hybrid nAChR expressed in Xenopus laevis oocytes. Although mutations of Thr77 in loop D of the ␤2 subunit resulted in a barely detectable effect on the imidacloprid concentration-response curve for the ␣4␤2 nAChR, T77R;E79V double mutations shifted the curve dramatically to higher affinity binding of imidacloprid. Likewise, T77K;E79R and T77N;E79R double mutations in the D␣2␤2 nAChR also resulted in a shift to a higher affinity for imidacloprid, which exceeded that observed for a single mutation of Thr77 to basic residues. By contrast, these double mutations scarcely influenced the ACh concentration-response curve, suggesting selective interactions with imidacloprid of the newly introduced basic residues. Computational, homology models of the agonist binding domain of the wild-type and mutant ␣4␤2 and D␣2␤2 nAChRs with imidacloprid bound were generated based on the crystal structures of acetylcholine binding proteins of Lymnaea stagnalis and Aplysia californica. The models indicate that the nitro group of imidacloprid interacts directly with the introduced basic residues at position 77, whereas those at position 79 either prevent or permit such interactions depending on their electrostatic properties, thereby explaining the observed functional changes resulting from site-directed mutagenesis.

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Section: Methodsmentioning

confidence: 99%

Role in the Selectivity of Neonicotinoids of Insect-Specific Basic Residues in Loop D of the Nicotinic Acetylcholine Receptor Agonist Binding Site

Shimomura¹,

Yokota²,

Ihara³

et al. 2006

Mol Pharmacol

118

116

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“…Although the leading compounds were not in the first wave, introducing the 6-chloro-3-pyridylmethyl and nitroimine moieties led to the development of the first new-type of nicotinic insecticide imidacloprid (Moriya et al, 1992;Kagabu, 1997). In parallel with synthesis, mode-of-action studies have been conducted to show that both early chemotypes, the nitromethylene heterocycles (Schroeder and Flattum, 1984;Sattelle et al, 1989;Leech et al, 1991) and imidacloprid (Bai et al, 1991) act on insect nAChRs.…”

mentioning

confidence: 99%

Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

Matsuda

Kanaoka²,

Akamatsu³

et al. 2009

Mol Pharmacol

118

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The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtypeselectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO 2 group of imidacloprid and 2) neonicotinoid-unique stacking and CHbonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-␣ nAChR subunits.

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“…The apparent preference for interaction at the high affinity site is comparable to that of SFX and it has been suggested that cis-neonicotinoids are useful compounds to discriminate between the two IMI binding sites. 132) However these compounds are the Michael adducts of crotonaldehydes with nitromethyleneimidazole (NMI), [133][134][135] a compound known since the early 1990's 66,136,137) and the authors have not ruled out the possible release of NMI in the aqueous experimental conditions. Indeed, unlike IMI, saturation studies using [ 3 H]-NMI detected only the presence of a single binding site.…”

Section: Sulfoximinesmentioning

confidence: 99%

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors

Crossthwaite

Bigot

Camblin

et al. 2017

Journal of Pesticide Science

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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 sapfeeding 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.

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1-(6-Chloronicotinyl)-2-nitroimino-imidazolidines and Related Compounds as Potential New Insecticides

Cited by 126 publications

References 0 publications

Role in the Selectivity of Neonicotinoids of Insect-Specific Basic Residues in Loop D of the Nicotinic Acetylcholine Receptor Agonist Binding Site

Role in the Selectivity of Neonicotinoids of Insect-Specific Basic Residues in Loop D of the Nicotinic Acetylcholine Receptor Agonist Binding Site

Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors

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