Structure-activity relationship of grayanotoxin derivatives using a tetrodotoxin-antagonized spasmodic response of brine shrimp larvae (Artemia salina)

Kinghorn, A. Douglas; Jawad, F.H.; Doorenbos, Norman J.

doi:10.1016/0041-0101(78)90083-1

Cited by 10 publications

(5 citation statements)

References 17 publications

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“…GrTx have acute toxic effects and the dose-effect relationships of some of them have been intensively investigated in mice (Hikino et al 1976). Further data were received from studies in skeletal muscle of frogs (Deguchi & Sakai 1967), rats (Fukuda et al 1974;Nishikawa et al 1989;Onat et al 1991) and brine shrimp larvae (Kinghorn et al 1978). The harmful effects of GrTx result from their binding to sodium channels of excitable membranes and the resulting inactivation of action potential.…”

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confidence: 98%

A case of human poisoning by grayanotoxins following honey ingestion: elucidation of the toxin profile by mass spectrometry

These

Bodi

Uecker

et al. 2015

Food Additives & Contaminants: Part A

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High-resolution mass spectrometry (HRMS) was applied for the detection of grayanotoxins (GrTx) in a contaminated honey sample. This sample was provided by a hospital due to a suspicion of intoxication after a patient had shown the typical symptoms of GrTx poisoning. Subsequent analysis proved the contamination with high amounts of GrTx and other toxins belonging to grayanane-type diterpenoids. This group of natural toxins is synthesised by the plant family Ericaceae and comprises more than 60 individual toxins, but only one compound is available as a reference standard. We applied a screening approach that easily confirms the presence or absence of GrTx without access to standards. By searching for predictable mass spectrometric fragment ions, including typical in-source fragments arising from collision-induced dissociation during electrospray ionisation, the complete toxin profile was screened and allowed the mass spectrometric identification of 15 individual GrTx. The potential of this approach is especially demonstrated by the fact that at least two of these toxins have not been previously described in the literature. A semi-quantitative estimation indicated a total toxin concentration of 358 mg kg(-1). An investigation of 49 honeys from the German retail market did not reveal the presence of GrTx.

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confidence: 98%

A case of human poisoning by grayanotoxins following honey ingestion: elucidation of the toxin profile by mass spectrometry

These

Bodi

Uecker

et al. 2015

Food Additives & Contaminants: Part A

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“…In sum, the integrity of the A ring was identified to be indispensable for this activity, and 2,3-expoxy, 6β-OH and 7α-OH were also vital for the maintenance of potent activity, which was further supported by other structure–bioactivity relationship studies, including stimulation of rat muscle spindle afferents and inhibition of brine shrimp motility (Figure ). , …”

Section: Antifeedant and Insecticidal Activity And Structure–activity...mentioning

confidence: 99%

“…133 In sum, the integrity of the A ring was identified to be indispensable for this activity, and 2,3-expoxy, 6β-OH and 7α-OH were also vital for the maintenance of potent activity, which was further supported by other structure−bioactivity relationship studies, including stimulation of rat muscle spindle afferents and inhibition of brine shrimp motility (Figure15). 134,135 Terpenoids, especially the grayanane diterpenoids, represent one category of structurally and biologically important secondary metabolites in Ericaceae. Their complex stereochemistry, various types of skeletons, and diverse biological activities have provided a general view of the conformational and biological roles of grayanoid functionality in these molecules.…”

Section: ■ Antifeedant and Insecticidal Activity And Structure−activi...mentioning

confidence: 99%

Structural Diversity and Biological Activity of the Genus Pieris Terpenoids

Yan

Zhang

et al. 2017

J. Agric. Food Chem.

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Secondary metabolites, particularly the grayanane diterpenoids produced by the members of genus Pieris, have been investigated in past decades for their remarkable antifeedant and insecticidal activities and toxicity. Grayanoids exhibit diverse biological properties such as antifeedant, insecticidal, cAMP regulatory, and sodium-channel-modulating activities. Structural complexity and diverse bioactivity of grayanoids have made them attractive targets for chemical, biological, and synthetic purposes. The current review synthesized findings published from 1966 to 2017, which include 135 reports that describe 130 terpenoids, including 103 grayanoids. The distribution, structure, skeleton, as well as the antifeedant and insecticidal activity of terpenoids, particularly the grayanane diterpenoids, are discussed in detail in this review. In cases where sufficient information is available, the structure-activity relationships of their antifeedant activity are also presented. We hope that this contribution will prompt more scientists to pay attention to these diterpenoids, which may be potentially applied in the agricultural field.

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“…In that study it became clear that the presence of 3/3-hydroxy and 10/3-methyl groups attached to the grayanane (A-nor-Bhomo-ent-kaurane) skeleton was essential for the development of PIE and that the potency was increased by acylation of the M^-hydroxy group. Kinghorn et al 4 described the structure-activity relationship of grayanotoxin derivatives using the spasmodic response of brine shrimp. They reported that 6-acylgrayanotoxin III (2) had some 20-30 times less activity than the mother substance, grayanotoxin III (G-III, 1); that 6,14-diacylates (3) were 2-3 times less effective than 6-acylates (2) in LD50 studies; and that the 3,6,14-triacylates 4 were inactive.…”

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confidence: 99%

“…Kinghorn et al 4 described the structure-activity relationship of grayanotoxin derivatives using the spasmodic response of brine shrimp. They reported that 6-acylgrayanotoxin III (2) had some 20-30 times less activity than the mother substance, grayanotoxin III (G-III, 1); that 6,14-diacylates (3) were 2-3 times less effective than 6-acylates (2) in LD50 studies; and that the 3,6,14-triacylates 4 were inactive. The toxic activity of 14-acylates 5 was not reported because of difficulty in preparing them.…”

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confidence: 99%

Quantitative structure-inotropy relationship applied to substituted grayanotoxins

Shirai¹,

Sakakibara²,

Kaiya³

et al. 1983

J. Med. Chem.

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Nine 14 beta-O-acylated grayanotoxins were synthesized by ozonolysis of 14,16-alkylidenegrayanotoxin III. The correlation between positive inotropic potency (PIE) in guinea pigs and physicochemical parameters (Vw, Mw, and Rm50) in 14 14-substituted grayanotoxins were quantitatively analyzed. It became clear that a parabolic relation existed between the bulkiness of the 14-substituents and PIE and that some electronic factor and the hydrophilic-hydrophobic balance would be related to the development of PIE.

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Structure-activity relationship of grayanotoxin derivatives using a tetrodotoxin-antagonized spasmodic response of brine shrimp larvae (Artemia salina)

Cited by 10 publications

References 17 publications

A case of human poisoning by grayanotoxins following honey ingestion: elucidation of the toxin profile by mass spectrometry

A case of human poisoning by grayanotoxins following honey ingestion: elucidation of the toxin profile by mass spectrometry

Structural Diversity and Biological Activity of the Genus Pieris Terpenoids

Quantitative structure-inotropy relationship applied to substituted grayanotoxins

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