Molecular Design of Neonicotinoids: Past, Present and Future

Kagabu, Shinzo

doi:10.1002/3527602038.ch16

Cited by 24 publications

(38 citation statements)

References 16 publications

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“…It is known that the extent of SA-responsive transcriptional changes varies depending upon the concentration of SA or SA analog, the timeframe for analyzing the response, and the assay system (10,12). Therefore, to determine whether the IMI-exclusive gene set of 3,508 is also associated with SA-dependent responses not identified in the parallel SA treatment, we compared our findings with those characterizing the early response to SA (13), obtained after treatment with the functional SA-analog S-methyl benzo [1,2,3] thiadiazole-7-carbothioate (BTH) (14), or identified as SAdependent in response to infection with powdery mildew using the Arabidopsis SA biosynthetic mutant ics1 (15). Thirty percent of the IMI-exclusive set were previously associated with SAdependent responses as ascertained by these studies.…”

Section: Neonicotinoids Induce Global Transcriptional Response Similamentioning

confidence: 99%

“…Imidacloprid (IMI), with a chloropyridinyl (Cl-pyr) substituent, is the most important neonicotinoid, used primarily as a systemic compound absorbed and translocated by plants to control sucking insect pests (1). The neonicotinoids clothianidin (2) (CLO) and a metabolic precursor, the oxadiazine compound thiamethoxam (3,4), which have chlorothiazolyl (Cl-thia) substituents, are also extensively used as systemic insecticides in plants.…”

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confidence: 99%

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Neonicotinoid insecticides induce salicylate-associated plant defense responses

Ford

Casida²,

Chandran³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

167

136

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Neonicotinoid insecticides control crop pests based on their action as agonists at the insect nicotinic acetylcholine receptor, which accepts chloropyridinyl-and chlorothiazolyl-analogs almost equally well. In some cases, these compounds have also been reported to enhance plant vigor and (a)biotic stress tolerance, independent of their insecticidal function. However, this mode of action has not been defined. Using Arabidopsis thaliana, we show that the neonicotinoid compounds, imidacloprid (IMI) and clothianidin (CLO), via their 6-chloropyridinyl-3-carboxylic acid and 2-chlorothiazolyl-5-carboxylic acid metabolites, respectively, induce salicylic acid (SA)-associated plant responses. SA is a phytohormone best known for its role in plant defense against pathogens and as an inducer of systemic acquired resistance; however, it can also modulate abiotic stress responses. These neonicotinoids effect a similar global transcriptional response to that of SA, including genes involved in (a)biotic stress response. Furthermore, similar to SA, IMI and CLO induce systemic acquired resistance, resulting in reduced growth of a powdery mildew pathogen. The action of CLO induces the endogenous synthesis of SA via the SA biosynthetic enzyme ICS1, with ICS1 required for CLO-induced accumulation of SA, expression of the SA marker PR1, and fully enhanced resistance to powdery mildew. In contrast, the action of IMI does not induce endogenous synthesis of SA. Instead, IMI is further bioactivated to 6-chloro-2-hydroxypyridinyl-3-carboxylic acid, which is shown here to be a potent inducer of PR1 and inhibitor of SA-sensitive enzymes. Thus, via different mechanisms, these chloropyridinyl-and chlorothiazolylneonicotinoids induce SA responses associated with enhanced stress tolerance.N eonicotinoids are the newest of the three major classes of insecticides, which also include the organophosphorus compounds and pyrethroids. Imidacloprid (IMI), with a chloropyridinyl (Cl-pyr) substituent, is the most important neonicotinoid, used primarily as a systemic compound absorbed and translocated by plants to control sucking insect pests (1). The neonicotinoids clothianidin (2) (CLO) and a metabolic precursor, the oxadiazine compound thiamethoxam (3, 4), which have chlorothiazolyl (Cl-thia) substituents, are also extensively used as systemic insecticides in plants. The neonicotinoids IMI and CLO are oxidatively cleaved in planta to 6-chloropyridinyl-3-carboxylic acid (CPA) and 2-chlorothiazolyl-5-carboxylic acid (CTA), respectively, among other metabolites (5). In studying metabolism of neonicotinoids in spinach (5) under insect-free conditions, we sometimes observed enhancement of foliage growth, plant vigor, and drought-tolerance. These remarkable effects of neonicotinoids directly on plants, independent of controlling insect pests, have also been noted by many researchers and farmers and documented in both research publications and patent disclosures, especially for IMI (6-8) and the CLO precursor, thiamethoxam (9). In addition, treatment with IMI...

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Section: Neonicotinoids Induce Global Transcriptional Response Similamentioning

confidence: 99%

mentioning

confidence: 99%

Neonicotinoid insecticides induce salicylate-associated plant defense responses

Ford

Casida²,

Chandran³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

167

136

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“…In the neonicotinoid field, questions regarding how the lipophilicity difference among the functional groups (dNNO 2 , dCHNO 2 , dNCN) or the cyclic/acyclic bioisosteres or the size difference among the alkyl substituents affects the biological response have been addressed (4,18).…”

Section: Introductionmentioning

confidence: 99%

Insecticidal and Neuroblocking Potencies of Variants of the Imidazolidine Moiety of Imidacloprid-Related Neonicotinoids and the Relationship to Partition Coefficient and Charge Density on the Pharmacophore

Kagabu

Ishihara

Hieda

et al. 2007

J. Agric. Food Chem.

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The pharmacophore of the neonicotinoid insecticide imidacloprid, nitroiminoimidazolidine, was modified to heterocycles such as thiazolidine, pyrrolidine, dihydroimidazole, dihydrothiazole, and pyridone conjugated to nitroimine (=NNO2) or nitromethylene (=CHNO2). Their 6-chloro-3-pyridylmethyl or 5-chloro-3-thiazolylmethyl derivatives were examined for insecticidal activity against the American cockroach by injection and for neuroblocking activity using the cockroach ganglion. Most of the compounds having the neonicotinoidal pharmacophore exhibited insecticidal activity at the nanomolar level, which was enhanced in the presence of synergists, and high neuroblocking activity at the micromolar level. Quantitative analysis for the compounds showed that the neuroblocking potency is proportional both to the Mulliken charge on the nitro oxygen atom and to the partition coefficient log P value. The equation for the insecticidal versus neuroblocking potencies indicated that both potencies are related proportionally with each other when the other factors are the same.

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“…TOMIZAWA CASIDA control in 1995. Many of the remaining gaps in pest control capabilities were filled recently by the neonicotinoids (Figure 1), which combine outstanding effectiveness with relatively low toxicity to vertebrates (3)(4)(5)(6)(7).…”

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confidence: 99%

NEONICOTINOID INSECTICIDE TOXICOLOGY: Mechanisms of Selective Action

Tomizawa

Casida

2005

Annu. Rev. Pharmacol. Toxicol.

1,458

1,028

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The neonicotinoids, the newest major class of insecticides, have outstanding potency and systemic action for crop protection against piercing-sucking pests, and they are highly effective for flea control on cats and dogs. Their common names are acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam. They generally have low toxicity to mammals (acute and chronic), birds, and fish. Biotransformations involve some activation reactions but largely detoxification mechanisms. In contrast to nicotine, epibatidine, and other ammonium or iminium nicotinoids, which are mostly protonated at physiological pH, the neonicotinoids are not protonated and have an electronegative nitro or cyano pharmacophore. Agonist recognition by the nicotinic receptor involves cation-pi interaction for nicotinoids in mammals and possibly a cationic subsite for interaction with the nitro or cyano substituent of neonicotinoids in insects. The low affinity of neonicotinoids for vertebrate relative to insect nicotinic receptors is a major factor in their favorable toxicological profile.

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Molecular Design of Neonicotinoids: Past, Present and Future

Cited by 24 publications

References 16 publications

Neonicotinoid insecticides induce salicylate-associated plant defense responses

Neonicotinoid insecticides induce salicylate-associated plant defense responses

Insecticidal and Neuroblocking Potencies of Variants of the Imidazolidine Moiety of Imidacloprid-Related Neonicotinoids and the Relationship to Partition Coefficient and Charge Density on the Pharmacophore

NEONICOTINOID INSECTICIDE TOXICOLOGY: Mechanisms of Selective Action

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