NOESY on neurotoxins: NMR and conformational assignments of picrotoxins

Perry, Nigel B.; Aiyaz, Mohammed; Kerr, Douglas S.; Lake, Robin; Leach, Meto T.

doi:10.1002/1099-1565(200101/02)12:1<69::aid-pca563>3.0.co;2-m

Cited by 16 publications

(30 citation statements)

References 12 publications

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“…In particular there were two prominent singlets in the 4.0 to 4.3 ppm region, where H-2 of tutin occurs as a singlet. 18 Preparative RPLC of this fraction, which required much care because of the weak UV absorption and the similar retention times of the peaks (9.00 and 9.35 min), led to the isolation of two tutin derivatives: glycosides 4 and 5. There were no other tutin glycosides detectable by 1 H NMR spectroscopy in the other RPLC fractions, and the NMR spectra of the two glycosides fully explained the NMR spectrum of the crude tutin glycoside fraction.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Sweet Poisons: Honeys Contaminated with Glycosides of the Neurotoxin Tutin

et al. 2015

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Poisonings due to consumption of honeys containing plant toxins have been reported widely. One cause is the neurotoxin tutin, an oxygenated sesquiterpene picrotoxane, traced back to honeybees (Apis mellifera) collecting honeydew produced by passionvine hoppers (Scolypopa australis) feeding on sap of the poisonous shrub tutu (Coriaria spp.). However, a pharmacokinetic study suggested that unidentified conjugates of tutin were also present in such honeys. We now report the discovery, using ion trap LC-MS, of two tutin glycosides and their purification and structure determination as 2-(β-d-glucopyranosyl)tutin (4) and 2-[6'-(α-d-glucopyranosyl)-β-d-glucopyranosyl]tutin (5). These compounds were used to develop a quantitative triple quadrupole LC-MS method for honey analysis, which showed the presence of tutin (3.6 ± 0.1 μg/g honey), hyenanchin (19.3 ± 0.5), tutin glycoside (4) (4.9 ± 0.4), and tutin diglycoside (5) (4.9 ± 0.1) in one toxic honey. The ratios of 4 and 5 to tutin varied widely in other tutin-containing honeys. The glycosidation of tutin may represent detoxification by one or both of the insects involved in the food chain from plant to honey.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Sweet Poisons: Honeys Contaminated with Glycosides of the Neurotoxin Tutin

et al. 2015

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“…However, in addition to the triterpenoids (lupenyl acetate, oleanolic acid, b-amyrin acetate, b-amyrin, friedelanone, friedelin acetate, a-amyrin and b-sitosterol) present in the plant material, there is potential for synergistic coupling with antimicrobial agents to improve therapeutic efficiency. [72][73][74] The shrub Osyris lanceolata (Santalaceae), also called 'African sandalwood', is used in traditional medicine in Botswana, South Africa, East Africa, Ethiopia and parts of Asia to treat a wide variety of diseases including; kidney infection, diarrhoea, cholera, coughs, malaria, gynaecological disorders, infertility, venereal diseases, cancer, and insanity. In vitro studies of the ethanolic extract of the fruits of the plant displayed a signicant anti-tyrosinase, antibacterial, and cytotoxic effects.…”

Section: -One (40)mentioning

confidence: 99%

“…It has been reported by several studies that compound 28 is the major neurotoxin in the New Zealand shrubs of the genus Coriaria and compound 29 is a major active component in toxic honey. [72][73][74] The shrub Osyris lanceolata (Santalaceae), also called 'African sandalwood', is used in traditional medicine in Botswana, South Africa, East Africa, Ethiopia and parts of Asia to treat a wide variety of diseases including; kidney infection, diarrhoea, cholera, coughs, malaria, gynaecological disorders, infertility, venereal diseases, cancer, and insanity. The ethnomedicinal applications of Osyris species in traditional medicine has been published in different parts of the world, including the NAPRALERT database 75 and the Prelude Medicinal Plants Database.…”

Section: Verbenaceaementioning

confidence: 99%

The chemistry and bioactivity of Southern African flora I: a bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes

et al. 2015

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As a whole, the African continent is highly endowed with a huge floral biodiversity. Natural products which have been isolated from plants growing in this region have shown interesting chemical structures with diverse biological activities, which could serve as a starting point for drug discovery. In this study, a literature survey led to the collection of 864 secondary metabolites from 101 plant species from 57 plant families. A correlation between the known biological activities of isolated compounds and the ethnobotanical uses of the plants has been attempted. This review is a survey of the bioactivities of alkaloids and terpenoids which have been isolated from Southern African flora versus the ethnobotanical uses of the plants used in Southern African traditional medicine.

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“…[9][10][11] Theoretical Calculations. Frontier Orbital Comparison between Coriamyrtin, Tutin, and Dihydrotutin With the aim of gaining insight into the origin of the activity trends found for 1-3 we carried out an electronic structure analysis by means of ab initio calculations.…”

Section: Phytochemical Analysismentioning

confidence: 99%

Inhibitory Activities on Mammalian Central Nervous System Receptors and Computational Studies of Three Sesquiterpene Lactones from Coriaria ruscifolia subsp. ruscifolia

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Manríquez-Navarro

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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Regular ArticleThe picrotoxin-like sesquiterpene lactones found in Anamirta paniculata and A. cocculus have generated longstanding theoretical interest, with early studies done in the 1960s and 1970s, to understand their mode of anticonvulsive action as potent transmission inhibitors in the central nervous system. The presence of an unusual carbon skeleton in the picrotoxin group of sesquiterpenes and in structurally related compounds generated crystallographic, biogenetic and conformational studies. Since then subsequent works have contributed to the study of many diseases associated to the central nervous system.The parameters used in the first structure-activity study of picrotoxins were media convulsive dose (CD 50 ) and LD 50 . The active compounds posses a lactone ring joining the C-3 and C-5 atoms (see 1), a tertiary hydroxyl group at C-6, and an isopropenyl group at C-4 (Chart 1). The study allowed selection of the active compounds and determined that the existence of the hydroxyl group, the lactone ring and the axial isopropenyl group played a determinant role in the activity on the central nervous system, although picrotoxin activity was not tested at the presynaptic inhibitory synapse level of the central nervous system. 1)The results of the assessment of picrotoxinin and related compounds activity, specifically picrotin, tutin (1), and coriamyrtin (2) on frog spinal cords were published twenty years later. The conclusions suggested that the presence of a hydroxyl group at C-6 could have a significant affinity for a gaminobutyric acid (GABA) effector chloride channel, an antagonist to the effects observed on g-aminobutyric acid but not on alanine or taurine. These experiments were tested on primary afferent terminals and for the antagonism of presynaptic inhibition. The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native g gaminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the...

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NOESY on neurotoxins: NMR and conformational assignments of picrotoxins

Cited by 16 publications

References 12 publications

Sweet Poisons: Honeys Contaminated with Glycosides of the Neurotoxin Tutin

Sweet Poisons: Honeys Contaminated with Glycosides of the Neurotoxin Tutin

The chemistry and bioactivity of Southern African flora I: a bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes

Inhibitory Activities on Mammalian Central Nervous System Receptors and Computational Studies of Three Sesquiterpene Lactones from Coriaria ruscifolia subsp. ruscifolia

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