Tertiary Alkaloids Research Articles

17-O-Acetyl,10-hydroxycorynantheol, a Selective Antiplasmodial Alkaloid Isolated fromStrychnos usambarensisLeaves

In the course of our investigations on Strychnos usambarensis leaves in order to isolate isostrychnopentamine, the main alkaloid responsible for the antiplasmodial activity of the plant, a new tertiary indolic alkaloid has been isolated: 17-O-acetyl,10-hydroxycorynantheol 1. Its structure was determined by means of spectroscopic and spectrometric methods such as UV, IR, CD, NMR, and ESI-MS. 17-O-acetyl,10-hydroxycorynantheol 1 is one of the most active monomeric indole alkaloids known to date showing an in vitro activity against Plasmodium falciparum close to 5 µM and a high selectivity.

Application of a new optimization strategy for the separation of tertiary alkaloids extracted from Strychnos usambarensis leaves

The HPLC separation of six alkaloids extracted from Strychnos usambarensis leaves has been developed and optimized by means of a powerful methodology for modelling chromatographic responses, based on three steps, i.e. design of experiments (DoE), independent component analysis (ICA) and design space (DS). This study was the first application of a new optimization strategy to a complex natural matrix. The compounds separated are the isomers isostrychnopentamine and strychnopentamine, 10-hydroxyusambarine and 11-hydroxyusambarine, also strychnophylline and strychnofoline. Three LC parameters have been optimized using a multifactorial design comprising 29 experiments that includes 2 center point replicates. The parameters were the percentage of organic modifiers used at the beginning of a gradient profile which consisted in different proportions of methanol (MeOH) and acetonitrile (MeCN), the gradient time to reach 70% of organic modifiers starting from the initial percentage and the percentage of MeCN found in the mobile phase. Subsequent to the experimental design application, predictive multilinear models were developed and used in order to provide optimal analytical conditions. The optimum assay conditions were: methanol/acetonitrile-sodium pentane sulfonate (pH 2.2; 7.5 mM) (33.4:66.6, v/v) at a mobile phase flow rate of 1 ml/min during a 40.6 min gradient time. The initial organic phase contained 3.7% MeCN and 96.3% MeOH. The method showed good agreement between the experimental data and predictive value throughout the studied parameters space. Improvement of the analysis time and optimized separation for the compounds of interest was possible due to the original and powerful tools applied. Finally, this study permitted the acquisition of isomers profiles allowing the identification of the optimal collecting period of S. usambarensis.

Screening for tertiary and quaternary alkaloids in some African Fagara species

Abstract A method has been described for the separate extraction of tertiary and quaternary alkaloids from plant material. Different thin-layer chromatographic systems have been used to separate compounds within each group of alkaloids. The methods have been applied to the screening of the barks of five Fagara species in which the presence of angoline, angolinine, skimmianine and, in some cases, 1-hydroxy-2,9,10-trimethoxy-NN-dimethylaporphinium chloride is indicated.

Antidiarrhoeal activity of bisnordihydrotoxiferine isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae).

Bisnordihydrotoxiferine, a dimeric tertiary indole alkaloid obtained from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), inhibited normal defaecation and castor oil, arachidonic acid, and magnesium sulphate-induced diarrhoea on intraperitoneal administration in mice. The effect may be related to the ability of the compound to decrease normal and castor oil-stimulated gastric emptying, small intestinal transit and water and electrolyte accumulation, and inhibition of normal colonic transit. As prostaglandins are involved in gastrointestinal functions, inhibition of their synthesis is likely to contribute to the anticathartic activity, which has never been reported before for an indole alkaloid.

The tertiary alkaloids of some asian species of strychnos.

The tertiary alkaloids of some asian species of strychnos.

The use of methylene chloride and chloroform for the extraction of tertiary alkaloids from Strychnos species.

The use of methylene chloride and chloroform for the extraction of tertiary alkaloids from Strychnos species.

Phytochemical screening and biological activity studies of five South African indigenous medicinal plants

Different extracts and fractions of five selected indigenous South African medicinal plants, namely, Cissampelos capensis, Geranium incanum and three Gethyllisspecies, were subjected to phytochemical screening and testing for cytotoxicity using the brine shrimp lethality bioassay, and antimicrobial activity assays against nine microbes, which included three fungal species, three Gram negative and three Gram positive bacteria. The majority of the extracts tested positive for the presence of tannins, phenolics and flavonoids, while in selected cases, phytochemical tests suggested the presence of essential oils, glycosides or alkaloids. The methanol extract of Gethyllis gregoriana displayed the highest cytotoxicity levels. Generally, the highest levels of biological activity were shown to reside in the methanolic extracts, while hexane extracts revealed very low to zero activity. The total tertiary alkaloid (TTA) of C. capensis was mostly active against Bacillus subtilis, a Gram +ve bacteria. The trends observed for the cytotoxicity assay were in agreement with those observed for the antimicrobial assay. Key words: Brine shrimp, lethality, medicinal plants, cytotoxicity, antimicrobial activity.

The mixture of tertiary and quaternary alkaloids isolated from Argemone ochroleuca inhibits spore germination of some fungi

The mixture of tertiary and quaternary alkaloids isolated from Argemone ochroleuca was separately assessed against spore germination of some plant pathogenic fungi, e.g. Alternaria alternata, Alternaria brassicae, Alternaria cajani, Bipolaris sp., Curvularia lunata, Curvularia sp., Colletotrichum musae, Fusarium udum, Helminthosporium sp., Helminthosporium pennisetti and Helminthosporium speciferum. Spore germination of Fusarium udum and Helminthosporium sp. was completely inhibited at very low concentration (200 ppm). A similar effect was observed on A. alternata, C. musae and H. pennisetti at 600, 800 and 1000 ppm. With quaternary alkaloids, Curvularia sp. and Colletotrichum musae were most sensitive as complete inhibition of spore germination was observed at 400, 600, 800 and 1000 ppm and a similar effect was observed with A. brassicae and A. cajani at 600, 800 and 1000 ppm. The remaining fungi were also highly sensitive to the mixture at different concentrations.

Two-Step Iron(0)-Mediated N-Demethylation of N-Methyl Alkaloids

A mild and simple two-step Fe(0)-mediated N-demethylation of a number of tertiary N-methyl alkaloids is described. The tertiary N-methylamine is first oxidized to the corresponding N-oxide, which is isolated as the hydrochloride salt. Subsequent treatment of the N-oxide hydrochloride with iron powder readily provides the N-demethylated amine. Representative substrates include a number of opiate and tropane alkaloids. Key intermediates in the synthesis of semisynthetic 14-hydroxy pharmaceutical opiates such as oxycodone and oxymorphone are also readily N-demethylated using this method.

Characterization of Aromatase Binding Agents from the Dichloromethane Extract of Corydalis yanhusuo Using Ultrafiltration and Liquid Chromatography Tandem Mass Spectrometry

Aromatase represents an important target for the treatment of hormone-dependent breast cancer. In the present study, nine alkaloids from the dichloromethane extract of Corydalis yanhusuo were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) and tested for their aromatase binding activities using an ultrafiltration LC-MS method by investigating the differences of peak areas of compounds before and after incubations with aromatase. It was demonstrated that the quaternary protoberberine alkaloids and the tertiary protoberberine alkaloids exhibited potent aromatase binding activities. The quaternary ammonium group and the methyl group at C-13 position of tertiary protoberberine alkaloids might be necessary for the activity. The findings should provide guidance for the discovery of potential aromatase inhibitors from natural products.

Acetylcholinesterase inhibitors from Stephania venosa tuber

Acetylcholinesterase (AChE) inhibitors have lately gained interest as potential drugs in the treatment of Alzheimer's disease. Three AChE inhibitors were isolated from tubers of a Thai medicinal plant, Stephania venosa (Bl) Spreng. They were identified as quaternary protoberberine alkaloids, stepharanine, cyclanoline and N-methyl stepholidine. They expressed inhibitory activity on AChE with IC50 values (concentration that caused 50% inhibition of activity) of 14.10 +/- 0.81, 9.23 +/- 3.47 and 31.30 +/- 3.67 microM, respectively. The AChE inhibitory activity of these compounds was compared with those of the related compounds, palmatine, jatrorrhizine and berberine, as well as tertiary protoberberine alkaloids isolated from the same plant, stepholidine and corydalmine. The results suggest that the positive charge at the nitrogen of the tetrahydroisoquinoline portion, steric substitution at the nitrogen, planarity of the molecule or substitutions at C-2, -3, -9, and -10 affect the AChE inhibitory activity of protoberberine alkaloids.

Triclisia sacleuxii (Pierre) Diels (Menispermaceae), a potential source of acetylcholinesterase inhibitors

Abstract Objectives To search for compounds possibly useful for the treatment of Alzheimer's disease. Methods Alkaloid fractions from the roots, stems and leaves of Triclisia sacleuxii (Menispermaceae) and pure bisbenzylisoquinoline alkaloids isolated from the roots (phaeanthine, N-methylapateline, 1,2-dehydroapateline and gasabiimine) were assessed for acetylcholin-esterase inhibitory activity. Key findings All extracts and compounds tested inhibited acetylcholinesterase to varying degrees; the leaf tertiary alkaloid fractions and the root quaternary alkaloid fractions exhibited the strongest inhibitory potential (90% at 0.1 mg/ml). The leaf tertiary alkaloid fraction was selected for further analysis (the quaternary alkaloids, which are too polar for absorption and brain distribution, were presumed to be clinically uninteresting). TLC bioautography using Ellman's reagent allowed the detection of acetylcholinesterase inhibitors and the isolation of the major active constituent, which was identified as lindoldhamine, a one-bridged bisbenzylisoquinoline alkaloid. Lindoldhamine displayed high acetylcholinesterase inhibitory activity with a 50% inhibition concentration in the micromolar range. Conclusions All T. sacleuxii alkaloid fractions tested exhibited anti-acetylcholinesterase activity; isolated bisbenzylisoquinoline alkaloids showed weak-to-high inhibition depending on their structural features. Structure modification could provide interesting derivatives with enhanced anti-acetylcholinesterase activity.

Antinociceptive effects of the extracts of Xylopia parviflora bark and its alkaloidal components in experimental animals

In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test.

<I>Triclisia sacleuxii</I> (Pierre) Diels (Menispermaceae), a potential source of acetylcholinesterase inhibitors

To search for compounds possibly useful for the treatment of Alzheimer's disease. Alkaloid fractions from the roots, stems and leaves of Triclisia sacleuxii (Menispermaceae) and pure bisbenzylisoquinoline alkaloids isolated from the roots (phaeanthine, N-methylapateline, 1,2-dehydroapateline and gasabiimine) were assessed for acetylcholinesterase inhibitory activity. All extracts and compounds tested inhibited acetylcholinesterase to varying degrees; the leaf tertiary alkaloid fractions and the root quaternary alkaloid fractions exhibited the strongest inhibitory potential (90% at 0.1 mg/ml). The leaf tertiary alkaloid fraction was selected for further analysis (the quaternary alkaloids, which are too polar for absorption and brain distribution, were presumed to be clinically uninteresting). TLC bioautography using Ellman's reagent allowed the detection of acetylcholinesterase inhibitors and the isolation of the major active constituent, which was identified as lindoldhamine, a one-bridged bisbenzylisoquinoline alkaloid. Lindoldhamine displayed high acetylcholinesterase inhibitory activity with a 50% inhibition concentration in the micromolar range. All T. sacleuxii alkaloid fractions tested exhibited anti-acetylcholinesterase activity; isolated bisbenzylisoquinoline alkaloids showed weak-to-high inhibition depending on their structural features. Structure modification could provide interesting derivatives with enhanced anti-acetylcholinesterase activity.

Systematic screening and characterization of tertiary and quaternary alkaloids from corydalis yanhusuoW.T. Wang using ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry

Ultra-performance liquid chromatography–quadrupole-time-of-flight mass spectrometry (UPLC–Q-TOF-MS) is an effective technique for analysis of complex samples with offering rapid, efficient separation in combination with accurate mass measurement and tandem mass spectrometry (MS/MS). This paper exploits this technique to identify the alkaloids in corydalis yanhusuo, an important antalgic Traditional Chinese Medicine (TCM). The mass spectral fragmentation behavior of one tertiary alkaloid and two quaternary alkaloids was studied in detail. Low-abundance product ions of tertiary and quaternary alkaloids were investigated and compared between each other. Sixteen alkaloids were screened out by using a systematic screening method developed in our laboratory; structures of eight therein were identified by characteristic UV absorption spectrum and positive ion mode of Q-TOF-MS/MS; and two of them were discovered for the first time in corydalis yanhusuo to our knowledge. This research demonstrates the potential of UPLC-Q-TOF-MS in structural characterization and identification of components in traditional Chinese herbal medicines.

Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D1 receptor.

Bioactivity-guided fractionation of Corydalis yanhusuo has resulted in the isolation of eight known isoquinoline alkaloids - tetrahydropalmatine, isocorypalmine, stylopine, corydaline, columbamine, coptisin, 13-methylpalmatine, and dehydro-corybulbine. The tertiary alkaloids were further analyzed by chiral HPLC to determine the ratios of d-and l-isomers. The isolated compounds were screened for their binding affinities at the dopamine D1 receptor. Isocorypalmine had the highest affinity (Ki = 83 nM). The structure-affinity relationships of these alkaloids are discussed.

Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents

A proposta deste trabalho foi de avaliar os efeitos da fracao de alcaloides terciarios totais (TTAF) de Cissampelos sympodialis Eichler (Menispermaceae) em dois modelos animais de depressao: a) teste do nado forcado e b) teste da reserpina. O tratamento de camundongos com TTAF (12,5 mg/kg) reduziu o tempo total de imobilidade dos animais. Tambem reverteu a hipotermia induzida por reserpina, demonstrando um efeito antidepressivo nos dois modelos. Adicionalmente, o tratamento com TTAF nao modificou a ambulacao e o comportamento de levantar das patas dianteiras dos animais avaliados no teste do campo aberto, realizado no intuito de investigar se a reducao no tempo de imobilidade apresentada no teste do nado forcado foi causada por estimulacao na atividade locomotora. Como a warifteina e um dos principais alcaloides presente na TTAF da C. sympodialis, e tem atividade inibidora da enzima fosfodiesterase, ela pode ser responsavel pelo efeito antidepressivo observado na fracao estudada.

Antiplasmodial and antitrypanosomal activity of Triclisia sacleuxii (Pierre) Diels

The antiplasmodial and antitrypanosomal activities of Triclisia sacleuxii (Pierre) Diels were investigated on three Plasmodium falciparum strains [FcB1, 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains] and on Trypanosoma brucei Tbsf 221. Roots, stems and leaves ethanolic extracts as well as crude tertiary and quaternary alkaloids fractions were considered. Whereas the ethanolic extracts and quaternary crude alkaloids fractions exhibited no significant activity, the roots and stems tertiary alkaloid fractions revealed interesting growth inhibition against the Plasmodium FcB1 and Trypanosoma Tbsf 221 strains. The IC(50) were 1.04 and 0.89 microg/ml for roots, 2.50 and 0.91 microg/ml for stems. The leaves tertiary alkaloids fraction also showed a promising antitrypanosomal activity (IC(50): 1.85 microg/ml). Phytochemical analysis of the roots tertiary alkaloids fraction yielded four major compounds, phaeanthine, N-methylapateline, 1,2-dehydroapateline and 1,2-dehydrotelobine, which were identified on the basis of their spectroscopic data. The four compounds displayed (in vitro) antitrypanosomal activity with IC(50) of 2.68, 1.19, 1.06 and 1.11 microM, respectively. They also demonstrated antiplasmodial activity on Plasmodium falciparum 3D7, with IC(50) of 1.72, 0.93, 1.39 and 12.4 microM respectively and on the chloroquine-resistant W2 with IC(50) of 0.35, 1.10, 1.63 and 1.52 microM.

Anti-malarial Berberine Alkaloids from Corydalis yanhusuo W.T. Wang

Corydalis yanhusuo W.T. Wang (C. turtschaninovii Bess. F. yanhusuo Y.H. Chou et C.C. Hsu) belongs to thePapaveraceae family. It is a perennial herb up to 30 cm tall, is one of the medicinally important species of corydalis, and is well known as a traditional Chinese herbal medicine [1]. C. yanhusuo is used in traditional Chinese medicine for the treatment of gastric and duodenal ulcer's, cardiac arrhythmia, rheumatism, and dysmenorrheal [2]. Also, it has been used to promote blood circulation, reinforce vital energy, and alleviate pain such as headache, chest pain, hypochondriac pain, abdominal pain, backache, arthralgia or trauma [3]. The genus Corydalis contains approximately 320 species and its tubers are exported to other countries. Seventy species have been used in traditional herbal remedies in China, Japan and Korea. The tuber contains several tertiary and quaternary ammonium alkaloids that form the main bioactive components. Some of the important quaternary ammonium alkaloids include dehydrocorydaline (DHC), palmatine, coptisine, and columbamine. These compounds have displayed various kinds of bioactivity [4–6]. For instance studies show that DHC not only inhibits antibody mediated allergic reactions but also influences cell mediated allergic reactions. One component tetrahydropalmatine (THP) is a very effective monoamine depletory in the brain [7]. This paper outlines the, structural determination of twelve known (1–12) compounds and their biological activity. Of the compounds, (3) and (4), showed IC50: 380, 130 (ng/ml); S. I: 12.5, 36.6 (ng/ml) anti-malarial activity. Acknowledgements: The work was supported by Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) NIH/NCRR grant number P20RR021929.

Rapid selective screening and determination of ephedrine alkaloids using GC‐MS footnote mark

Ephedra (ma huang) has been widely used as an herb or herbal extract in both traditional Chinese medicine and Western world dietary supplements. The effects of Ephedra have been attributed to a series of six ephedrine alkaloids including ephedrine and pseudoephedrine. A GC-MS method for the ephedrine alkaloids is described which couples ammoniacal chloroform as the extraction solvent with a two-stage derivatisation scheme. This scheme produces the O-trimethylsilyl, N-trifluoracetyl derivatives (O-TMS, N-TFA) for the primary and secondary amine alkaloids, and the O-TMS derivatives for the tertiary amine alkaloids. Relatively clean extracts are obtained from complex matrices, and the six ephedrine alkaloids are effectively separated and identified. This approach was also evaluated for quantitative analysis, and was shown to provide quantitative results for ephedrine and pseudoephedrine, and good estimates for the four minor alkaloids. Figures of merit are presented for linearity, detection limits, precision and accuracy. We have applied this approach to the rapid screening and profiling of the ephedrine alkaloids in whole Ephedra plants, liquid plant extracts, dried powder plant extracts and a variety of Ephedra-containing dietary supplements.