Christian Zidorn

Sesquiterpene lactones and their precursors as chemosystematic markers in the tribe Cichorieae of the Asteraceae.

This review summarizes all reports on sesquiterpene lactones and their immediate precursors from the Cichorieae (Lactuceae) tribe of the Asteraceae. A total of 360 compounds have been reported from this tribe. The reported substances belong to three classes of sesquiterpenoids: guaianolides (243 compounds), eudesmanolides (73 compounds), and germacranolides (44 compounds). Sources of these compounds encompass 139 taxa from 31 different genera. The distribution of these lactones within the tribe Cichorieae is discussed in a chemosystematic context. Moreover, some general ideas about the interpretation of chemosystematic data are discussed.

Quantitative analysis of flavonoids and phenolic acids in Arnica montana L. by micellar electrokinetic capillary chromatography

Arnica montana preparations have been used in Europe for centuries to treat skin disorders. Among the biologically active ingredients in the flower heads of the plant are sequiterpenes, flavonoids and phenolic acids. For the simultaneous determination of compounds belonging to the latter two groups a micellar electrokinetic capillary chromatography (MEKC) method was developed and validated. By using an electrolyte solution containing 50 mM borax, 25 mM sodium dodecyl sulfate and 30% of acetonitrile the separation of seven flavonoids and four caffeic acid derivatives was feasible in less than 20 min. The optimized system was validated for repeatability (sigma(rel) < or = 4.4%), precision (inter-day sigma(rel) < or = 8.13%, intra-day sigma(rel) < or = 4.32%), accuracy (recovery rates from 96.8 to 102.4%), sensitivity (limit of detection (LOD) < or = 4.5 microg mL(-1)) and linearity (R(2) > or = 0.9996), and then successfully applied to assay several plant samples. In all of them the most dominant flavonoid was found to be quercetin 3-O-glucuronic acid, whereas 3,5-dicaffeoylquinic acid was the major phenolic acid; the total content of flavonoids and phenolic acids varied in the samples from 0.60 to 1.70%, and 1.03 to 2.24%, respectively.

Altitudinal Variation of Secondary Metabolite Profiles in Flowering Heads of Matricaria chamomilla cv. BONA

The altitudinal variation of the contents of secondary metabolites in flowering heads of Matricaria chamomilla L. (Asteraceae) was assessed. Plants of M. chamomilla cultivar BONA were grown in nine experimental plots at altitudes between 590 and 2,230 m at Mount Patscherkofel near Innsbruck/Austria. The amounts of flavonoids and phenolic acids were quantified by HPLC/DAD. For both flavonoids and phenolic acids positive (r = 0.559 and 0.587) and statistically significant (both p < 0.001) correlations with the altitude of the growing site were observed. The results are compared to previous results on Arnica montana L. cv. ARBO. Moreover, various ecological factors, which change with the altitude of the growing site, are discussed as potential causes for the observed variation.

Tyrolobibenzyls E and F from Scorzonera humilis and distribution of caffeic acid derivatives, lignans and tyrolobibenzyls in European taxa of the subtribe Scorzonerinae (Lactuceae, Asteraceae).

A chemosystematic study of the subtribe Scorzonerinae, a subtribe of the Lactuceae tribe of the Asteraceae family was performed, using the recently discovered tyrolobibenzyls as well as lignans and caffeic acid derivatives as diagnostic characters. In addition to the known compounds two new tyrolobibenzyls (E and F) were isolated and their structures were established by mass spectrometry and 1D and 2D NMR spectroscopy. Twenty four samples from rootstocks of seventeen different Scorzonerinae taxa, comprising members of three genera (Podospermum, Scorzonera, and Tragopogon), were analyzed. Tyrolobibenzyls A (1), B (2), C (5), D (3), E (6), and F (4) were identified in crude extracts by means of HPLC retention times, on-line UV spectra and on-line MS/MS spectra. Quantification of these compounds was performed by HPLC, using 2,2-bis-(4-hydroxyphenyl)-propane as an internal standard. Tyrolobibenzyls A-F were only detected in samples from Scorzonera humilis, while chlorogenic acid and 3,5-dicaffeoylquinic acid were detected in all samples investigated. In contrast, caffeoyl tartaric acid and cichoric acid were not detectable in any member of the subtribe Scorzonerinae.

Tyrolobibenzyls - Novel Secondary Metabolites from Scorzonera humilis

Tyrolobibenzyls A (2), B (3), and C (4) were isolated from Scorzonera humilis (Asteraceae) of Tyrolean origin. Compounds 2 and 3 possess a unique phenylethyl-benzofuran backbone and represent a new class of natural compounds. Structural assignments are based on 1D and 2D NMR as well as MS data. Furthermore, peracetylated derivatives of compounds 3 and 4 were synthesized. Pharmacological evaluation of these compounds by the [3H]thymidine assay showed no pronounced cytotoxicity.

Eudesmanolides and inositol derivatives from Taraxacum linearisquameum

Abstract The methanol extract of subaerial parts of Taraxacum linearisquameum Soest afforded two eudesmane type sesquiterpene lactones, 2 β -hydroxysantamarine-1 β - d -glucopyranoside ( 2 ) and 3 β -hydroxy-4 αH -3-dihydrosantamarine- β - d -glucopyranoside ( 3 ) and two inositol derivatives, (1S,2S,4R,5S)-2,3,4,6-tetrahydroxy-5-[2-(4-hydroxyphenyl)acetyl]oxycyclohexyl-2-(4-hydroxyphenyl)acetate ( 4 ) and (2S,3R,5R,6S)-2,3,5,6-tetrahydroxy-4-[2-(4-hydroxyphenyl)acetyl]oxycyclohexyl-2-(4-hydroxy-phenyl)acetate ( 5 ). Additionally, the known compound taraxinic acid β - d -glucopyranosyl ester ( 1 ) has been isolated.

Structure of Tyrolobibenzyl D and Biological Activity of Tyrolobibenzyls from Scorzonera humilis

A novel tyrolobibenzyl derivative, 1→6-β-ᴅ-apiosyl-β-ᴅ-glucopyranosyl 4-[2-(4-hydroxyphenyl) ethyl]benzofuran-2-carboxylate 3 (tyrolobibenzyl D) was isolated from Scorzonera humilis L. and its structure established by mass spectrometry and 1D- and 2D-NMR spectroscopy. The biological activities of the new compound and related tyrolobibenzyls A-C (1-2, 4) and the semi-synthetic peracetyl derivatives of tyrolobibenzyls B (2a) and C (4a) were assessed. The results revealed no cytotoxic activity against P388 cells and neither anti-bacterial activity against Bacillus subtilis nor antifungal activity against Candida albicans and Trichophyton mentagrophytes for any of the investigated compounds. An evaluation of potential chemopreventive activity of 2, 2a, 4, and 4a also revealed no pronounced activity in any of the employed assaying systems.

Antimyeloma activity of the sesquiterpene lactone cnicin: impact on Pim-2 kinase as a novel therapeutic target

Despite recent advances in therapy, multiple myeloma, the second most common hematologic tumor in the Western world, is still incurable. Identification of substances that display a wide range of tumor-killing activities and target cancer-specific pathways constitute a basis for the development of novel therapies. In this study, we investigate the cytotoxic effect of the natural substance cnicin in multiple myeloma. Cnicin treatment reveals potent antiproliferative effects and induces cell death in cell lines and primary myeloma cells even in the presence of survival cytokines and the tumor microenvironment. Other cell lines of hematopoietic origin also succumb to cell death whereas stromal cells and endothelial cells are unaffected. We show that activation of caspases, accumulation of reactive oxygen species and downregulation of nuclear factor kappa-light-chain-enhancer of activated B cell contribute to the cytotoxic effects of cnicin. Microarray analysis reveals downregulation of Pim-2, a serine/threonine kinase. We provide evidence that Pim-2 constitutes a new survival kinase for myeloma cells in vitro and is highly expressed in malignant but not in normal plasma cells in vivo. Combining cnicin with current standard or experimental therapeutics leads to enhanced cell death. Thus, our data indicate that cnicin induces myeloma cell death via several pathways and reveals Pim-2 as a novel target. These findings provide a rational for further evaluation of cnicin as a new anti-tumor drug and underline the potential of sesquiterpene lactones in tumor therapy.

Chemosystematic investigations of irregular diterpenes in Anisotome and related New Zealand Apiaceae

A chemosystematic HPLC-UV and HPLC-MS investigation of New Zealand members of the Apiaceae was performed. Diterpenes were identified and quantified in methanolic extracts from subaerial parts of 28 taxa and 54 samples of Aciphylla, Anisotome, Apium, Gingidia, Lignocarpa, Oreomyrrhis, and Scandia. Six diterpenes (1-2, 4-7) and four polyacetylenes (8-11) were identified. The known compounds were the diterpenes anisotomenoic acid 1, anisotomene-1-ol 2, 16-acetoxyanisotomenoic acid 4 and anisotomene-1,12-diol 5; and the polyacetylenes falcarinol 8, falcarindiol 9, (+)-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol 10, and (+)-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol 1-acetate 11. New irregular diterpenes 13,14-dihydroanisotom-12E-ene-1,14-diol 6 and 14-methoxy-13,14-dihydroanisotom-12E-ene-1-ol 7 were isolated from A. haastii. Isomers of the new semi-synthetic diterpene 16-hydroxyanisotomenoic acid 3 were detected in extracts of Anisitone flexuosa. Structure elucidation was performed by HR mass spectrometry and 1D and 2D NMR spectroscopy. In crude extracts, compounds were identified by their HPLC retention times and their on-line HPLC-UV and MS spectra. Anisotomene diterpenes occurred in eight out of 16 species of the genus Anisotome, but were not detected in any of the other genera. In contrast, polyacetylenes were present in all the genera investigated.

Analysis of rare flavonoid C-glycosides in Celtis australis L. by micellar electrokinetic chromatography

This manuscript reports on the first analytical procedure for the determination of flavonoids in Celtis australis. The capillary electrophoretic separation of 8 compounds, most of them flavone C-glycosides, was possible using a borax buffer with pH 9.0, which contained 25mM SDS as detergent and 7.5% of n-butanol as organic modifier. Method validation revealed that the developed assay is repeatable (sigma(rel)<or=4.0%), precise (inter-day sigma(rel)<or=6.7%, intra-day sigma(rel)</=3.9%), accurate (recovery rates from 96.8 to 102.3%), sensitive (LOD: 2.2-1.6microg/ml) and linear (R(2)>or=0.9996) within the tested concentration range. The quantitative analysis of several C. australis samples showed that isovitexin is the most abundant representative (0.06-0.09%), at a rather uniform content of total flavonoids of approx. 0.3% in all specimens.