Application of NMR to Identification of Metabolites

Scientific conference (2006, April 07)

Study of the interaction of antiplasmodial strychnine derivatives with the glycine receptor

in European Journal of Pharmacology (2006), 530(1-2), 15-22

Strychnos icaja Baill. (Loganiaccae) is a liana found in Central Africa known to be an arrow and ordeal poison but also used by traditional medicine to treat malaria. Recently, many dimeric or trimeric ... [more ▼]

Strychnos icaja Baill. (Loganiaccae) is a liana found in Central Africa known to be an arrow and ordeal poison but also used by traditional medicine to treat malaria. Recently, many dimeric or trimeric indolomonoterpenic alkaloids with antiplasmodial properties have been isolated from its rootbark. Since these alkaloids are derivatives of strychnine, it was important, in view of their potential use as antimalarial drugs, to assess their possible convulsant strychnine-like properties. In that regard, their interaction with the strychnine-sensitive glycine receptor was investigated by whole-cell patch-clamp recordings on glycine-gated currents in mouse spinal cord neurons in culture and by [H-3]strychnine competition assays on membranes from adult rat spinal cord. These experiments were carried out on sungucine (leading compound of the chemical class) and on the antiplasmodial strychnogucine B (dimeric) and strychnohexamine (trimeric). In comparison with strychnine, all compounds interact with a very poor efficacy and only at concentrations > I mu M with both [H-3]strychnine binding and glycine-gated currents. Furthermore, the effects of strychnine and protostrychnine, a monomeric alkaloid (without antiplasmodial activity) also isolated from S. icaja and differing from strychnine only by a cycle opening, were compared in the same way. The weak interaction of protostrychnine confirms the importance of the G cycle ring structure in strychnine for its binding to the glycine receptor and its antagonist properties. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

Chemical and biological investigations of a toxic plant from Central Africa, Magnistipula butayei subsp. montana.

in Journal of Ethnopharmacology (2006), 103(3), 433-8

Magnistipula butayei subsp. montana (Chrysobalanaceae) is known, in the Great Lakes Region, to possess toxicological properties. In this paper, we investigated the acute toxicity (dose levels 50-1600 mg ... [more ▼]

Magnistipula butayei subsp. montana (Chrysobalanaceae) is known, in the Great Lakes Region, to possess toxicological properties. In this paper, we investigated the acute toxicity (dose levels 50-1600 mg/kg) of its aqueous extract, administered orally to adult Wistar rats. This study demonstrated that the freeze-dried aqueous extract (5%, w/w) possesses high toxicity. The extract caused hypothermia, neurological disorders, including extensor reflex of maximal convulsive induced-seizures at about 2 h after the administered dose, and death occurred (LD50=370 mg/kg) in a dose dependent manner. Blood parameter evaluation revealed slight variations, but these might not have clinical relevance. Histological examination of internal organs (lungs, liver, heart and kidneys) did not reveal any abnormality in the treated group compared to the control. Therefore, it can be concluded that Magnistipula butayei subsp. montana aqueous extract, given orally, is toxic and that its target is the central nervous system. General phytochemical screening revealed that the plant did not contain significant amounts of products known to be toxic, such as alkaloids or cardioactive glycosides, but only catechic tannins, amino acids, saponins and other aphrogen principles in the three parts of the species (fruit, leave and bark). [less ▲]

Metabolomic analysis of Strychnos species extracts by 1 H nuclear magnetic resonance spectrometry and multivariate analysis techniques

Conference (2005, August 22)

In vitro screening of some Strychnos species for antiplasmodial activity

in Journal of Ethnopharmacology (2005), 97(3), 535-539

The antiplasmodial activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl ... [more ▼]

The antiplasmodial activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl acetate (EtOAc) extracts were analysed and, for the most active species, methanolic (MeOH) extracts were also tested. Among them, Strychnos variabilis De Wild. seemed to be very promising (inhibitory concentration 50% (IC50) < 5 microg/ml) whereas two other species, Strychnos gossweileri Exell and Strychnos mellodora S. Moore, could be interesting (IC50 < 15 microg/ml) in further antimalarial studies. [less ▲]

Metabolomic analysis of Strychnos nux-vomica, Strychnos icaja and Strychnos ignatii extracts by H-1 nuclear magnetic resonance spectrometry and multivariate analysis techniques

in Phytochemistry (2004), 65(13), 1993-2001

H-1 Nuclear magnetic resonance spectrometry and multivariate analysis techniques were applied for the metabolic profiling of three Strychnos species: Strychnos nux-vomica (seeds, stem bark, root bark ... [more ▼]

H-1 Nuclear magnetic resonance spectrometry and multivariate analysis techniques were applied for the metabolic profiling of three Strychnos species: Strychnos nux-vomica (seeds, stem bark, root bark), Strychnos ignatii (seeds), and Strychnos icaja (leaves, stem bark, root bark, collar bark). The principal component analysis (PCA) of the H-1 NMR spectra showed a clear discrimination between all samples, using the three first components. The key compounds responsible for the discrimination were brucine, loganin, fatty acids.. and Strychnos icaja alkaloids such as icajine and sungucine. The method was then applied to the classification of several "false angostura" samples. These samples were, as expected, identified as S. nux-vomica by PCA, but could not be clearly discriminated as root bark or stem bark samples after further statistical analysis. (C) 2004 Published by Elsevier Ltd. [less ▲]

LC/MS/NMR analysis of isomeric divanilloylquinic acids from the root bark of Fagara zanthoxyloides Lam

in Phytochemistry (2004), 65(8), 1145-1151

Gradient HPLC coupled to DAD/UV, MS/MS and NMR has been applied to the rapid structure determination of three new isomeric divanilloylquinic acids from Fagara zanthoxyloides collected in Burkina Faso: 3,4 ... [more ▼]

Gradient HPLC coupled to DAD/UV, MS/MS and NMR has been applied to the rapid structure determination of three new isomeric divanilloylquinic acids from Fagara zanthoxyloides collected in Burkina Faso: 3,4-O-divanilloylquinic acid, 3,5-O-divanilloylquinic acid and 4,5-O-divanilloylquinic acid. Furthermore these new compounds named burkinabins A-C could play a useful role in sickle cell disease, as the active agents of Fagara zanthoxyloides are said to be unidentified aromatic compounds with carboxylic acid grouping (Adesanya, S.A., Sofowora, A., 1983. Biological standardisation of Zanthoxylum roots for antisickling activity. Planta Med. 48, 27-33). (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

Alkaloid accumulation in Catharanthus roseus cell suspension cultures fed with stemmadenine

in Biotechnology Letters (2004), 26(10), 793-798

Feeding stemmadenine to Catharanthus roseus cell suspension culture resulted in the accumulation of catharanthine, tabersonine and condylocarpine. Condylocarpine is not an intermediate in the pathway to ... [more ▼]

Feeding stemmadenine to Catharanthus roseus cell suspension culture resulted in the accumulation of catharanthine, tabersonine and condylocarpine. Condylocarpine is not an intermediate in the pathway to catharanthine or tabersonine when it is fed to the cultures. The results support the hypothesis that stemmadenine is an intermediate in the pathway to catharanthine and tabersonine. [less ▲]

First and second generations of COX-2 selective inhibitors

in Mini Reviews in Medicinal Chemistry (2004), 4

Quantitative analysis of strychnine and brucine in Strychnos nux-vomica using H-1-NMR

in Planta Medica (2003), 69(12), 1169-1171

A quantitative analysis using H-1-NMR (Q-NMR) has been developed for the determination of strychnine and brucine in Strychnos nux-vomica seeds and stems. The advantages of the method are that no reference ... [more ▼]

A quantitative analysis using H-1-NMR (Q-NMR) has been developed for the determination of strychnine and brucine in Strychnos nux-vomica seeds and stems. The advantages of the method are that no reference alkaloids are needed for calibration curves, the quantification could be directly realized on a crude extract, strychnine and brucine could easily be distinguished, an overall profile of the preparation (including non alkaloid compounds) could be directly obtained, and a very significant time-gain could be achieved, in comparison to conventional HPLC methods, for instance. [less ▲]