New Insecticidally Active Derivatives of Nereistoxin

KONISHI, Kazuo

doi:10.1271/bbb1961.32.678

Cited by 9 publications

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“…Thiosulfonates are a family of valuable compounds that have shown insecticidal activity in azuki bean weevils and rice stem borer larvae. 18 In addition, thiosulfonates can act as a thiotransfer reagent for the preparation of a variety of thiolated compounds. 19 Interestingly, no methods for the preparation of trifluoromethylthiolated sulfonates have been reported previously.…”

Section: ■ Introductionmentioning

confidence: 99%

Structure–Reactivity Relationship of Trifluoromethanesulfenates: Discovery of an Electrophilic Trifluoromethylthiolating Reagent

et al. 2015

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A family of electrophilic trifluoromethanesulfenates was prepared. Structure-reactivity relationship studies showed that the substituted groups on the aryl ring of the trifluoromethylthiolating reagent did not have an obvious influence on their reactivities. A simplified electrophilic trifluoromethylthiolating reagent 1c was then identified that can react with a wide range of nucleophiles such as Grignard reagents, arylboronic acids, alkynes, indoles, β-ketoesters, oxindoles, and sodium sulfinates under mild reaction conditions. A variety of functional groups were tolerated under these conditions.

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Section: ■ Introductionmentioning

confidence: 99%

Structure–Reactivity Relationship of Trifluoromethanesulfenates: Discovery of an Electrophilic Trifluoromethylthiolating Reagent

et al. 2015

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“…Nereistoxin (NTX), a naturally occurring insecticide in the marine worm Lumbriconereis heteropoda ( , ), was the lead compound optimized for the synthetic insecticides cartap ( Figure ) and bensultap ( − ). Cartap and its dithiol ester analogues may be proinsecticides which are converted metabolically in the insect body to NTX ( , ), which then competes with acetylcholine (ACh) to block the nAChR-mediated signal ( , ).…”

Section: Introductionmentioning

confidence: 99%

Nereistoxin and Cartap Neurotoxicity Attributable to Direct Block of the Insect Nicotinic Receptor/Channel

Lee

Tomizawa

Casida

2003

J. Agric. Food Chem.

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Nereistoxin (NTX) (4-dimethylamino-1,2-dithiolane) is the naturally occurring prototype for cartap [the bis(thiocarbamate) derivative of the NTX dithiol], which is generally regarded as a proinsecticide reverting to NTX. The aim of this study is to define the target site(s) for dithiolanes and dithiol esters. The affinity of [(3)H]NTX was not suitable for binding assays with honeybee (Apis mellifera) head membranes. However, NTX and cartap are equally potent, direct-acting, and competitive displacers of [(3)H]thienylcyclohexylpiperidine binding at the noncompetitive blocker (NCB) site of the Apis nicotinic acetylcholine receptor (nAChR)/channel. NTX also binds at the Apis [(3)H]imidacloprid agonist site, but cartap does not. As candidate metabolic pathways, sequential N-desmethylation and S-oxidation of NTX progressively reduce its potency at the NCB site and toxicity to houseflies. A P450 inhibitor reduces the toxicity of NTX and enhances it with cartap. Surprisingly, cartap is not just a pro-NTX but instead directly induces inhibitory neurotoxicity by blocking the nAChR/channel, whereas NTX may have dual NCB and agonist targets.

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“…Nicotinoids and neonicotinoids act as agonists, inducing excitatory neurotoxicity ( − ). On the other hand, cartap and bensultap (two commercial insecticides) ( − ) and nereistoxin (NTX) (their natural product prototype) ( , ) ( Figure ) have the opposite action; that is, they are blockers causing inhibitory neurotoxicity ( 5 , 7 , 10−18 ). Interestingly, the different mechanisms of action (nicotinic agonists versus blockers) should circumvent possible cross-resistance at the nAChR.…”

Section: Introductionmentioning

confidence: 99%

Cartap Hydrolysis Relative to Its Action at the Insect Nicotinic Channel

Lee

Caboni

Tomizawa

et al. 2003

J. Agric. Food Chem.

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The insecticide cartap is the bis(thiocarbamate) derivative of 2-(dimethylamino)propane-1,3-dithiol, which on oxidation forms the natural toxicant nereistoxin (NTX) [4-(dimethylamino)-1,2-dithiolane]. Both cartap and NTX are ion channel blockers of the nicotinic acetylcholine receptor (nAChR). Cartap was originally proposed to act only after metabolic conversion to NTX and later suggested to block directly without activation. The present study uses a new approach to differentiate these hypotheses, that is, pH effects on channel-blocking activity and hydrolysis rates. As controls, mecamylamine (the classic channel blocker) and NTX are stable and similar in channel-blocking potency ([(3)H]thienylcyclohexylpiperidine binding assay, honeybee nAChR) at pH 6.1-8.4. In contrast, cartap is >200-fold more effective at pH 7.4 than at pH 6.1, indicating that it undergoes hydrolytic activation. Cartap slowly hydrolyzes to cartap monothiol at pH 6.1 but quickly forms the dithiol and some NTX at pH 7.4. The relationship between potency and hydrolysis products at various pH ranges suggests that cartap dithiol is the most plausible blocking agent.

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New Insecticidally Active Derivatives of Nereistoxin

Cited by 9 publications

References 0 publications

Structure–Reactivity Relationship of Trifluoromethanesulfenates: Discovery of an Electrophilic Trifluoromethylthiolating Reagent

Structure–Reactivity Relationship of Trifluoromethanesulfenates: Discovery of an Electrophilic Trifluoromethylthiolating Reagent

Nereistoxin and Cartap Neurotoxicity Attributable to Direct Block of the Insect Nicotinic Receptor/Channel

Cartap Hydrolysis Relative to Its Action at the Insect Nicotinic Channel

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