Publications by authors named "Michael Spiteller"

185 Publications

Cytotoxic Compounds from the Stem Bark of Two subsp. of .

J Nat Prod 2021 05 11;84(5):1453-1458. Epub 2021 May 11.

Department of Chemistry, Faculty of Sciences, Egerton University, P.O. Box 536, 20115 Egerton, Kenya.

Three new bufadienolides, namely, paulliniogenin A (), paulliniogenin B (), and 16β-formyloxybersamagenin 1,3,5-orthoacetate (), together with two known bufadienolides and six known phenolic substances, were isolated from the stem bark of subsp. and subsp. . The structures of the compounds were elucidated based on their NMR and HRMS data analyses. The relative configurations were defined by single-crystal X-ray crystallography and NOESY correlations. Cytotoxicity against the L929 and KB3.1 cancer cell lines of the isolated compounds was investigated using an MTT assay. Paulliniogenin A () and 16β-hydroxybersamagenin-1,3,5-orthoacetate () showed cytotoxicity against the KB3.1 cell line with IC values of 1.4 ± 0.77 and 1.6 ± 0.81 μM, respectively. Moreover, paulliniogenin A () and paulliniogenin B () demonstrated weak activity against .
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http://dx.doi.org/10.1021/acs.jnatprod.0c01141DOI Listing
May 2021

Cytotoxic alkaloids from the root of (mildbr) Kokwaro.

Nat Prod Res 2021 May 8:1-8. Epub 2021 May 8.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Dortmund, Germany.

Chemical investigation of the root of afforded 1 new alkamide derivative, (2,4)-6-oxo--isobutyldeca-2,4-dienamide () together with 10 known congeners including one phenolic amide (), four benzophenanthridines (), three indolonaphthyridines () and two lignans ( and ). Their structures were elucidated by a combination of spectroscopic and spectrometric data. Using resazurin reduction assay, the crude extract (10 µg/mL) and isolates (10 µM) were screened for their cytotoxic activities against the drug-sensitive (CCRF-CEM) leukemia cell line and its multidrug-resistant counterpart (CEM/ADR5000). Compounds , and showed cytotoxicity against CCRF-CEM with IC values of 2.00 ± 0.33, 2.31 ± 0.20 and 0.11 ± 0.04 µM, respectively. Only compound exhibited strong cytotoxic activity against CEM/ADR5000 with an IC value of 2.34 ± 0.34 µM in comparison with the standard drug doxorubicin which showed IC values of 0.01 ± 0.14 (CCRF-CEM) and 26.78 ± 3.30 µM (CEM/ADR5000).
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http://dx.doi.org/10.1080/14786419.2021.1913586DOI Listing
May 2021

Impact of Nonylphenols and Polyhalogenated Compounds in Follicular Fluid on the Outcome of Intracytoplasmic Sperm Injection.

Reprod Sci 2021 Feb 23. Epub 2021 Feb 23.

Fertility Center Dortmund, Olpe 19, D-44135, Dortmund, Germany.

Endocrine-disrupting chemicals (EDCs) interfere with the mammalian hormone system and alter its endo- and paracrine regulation. The goal of the present study was to examine the presence of 14 EDCs, including the technical mixture of nonylphenols and Mirex, in human follicular fluid (FF) and to find a potential correlation between endocrine active substances and a possible impact on female fertility. Furthermore, potential sources of EDC exposition regarding patients' lifestyle and socioeconomic factors were investigated. Human FF was collected from a total of 210 women undergoing intracytoplasmic sperm injection-treatment cycles because of male subfertility. The presence of EDCs was analyzed using gas chromatography coupled with mass spectrometry. Thirteen of the 14 investigated EDCs were present in every FF sample; compounds with the highest concentrations in FF were nonylphenol and Mirex. Nearly all kinds of EDCs led to significantly reduced maturation and fertilization rate. No significant influence of EDC concentration on the clinical pregnancy rate was observed for neither of the analyzed EDCs. Patients who obtained their clothes and textiles at fashion discounters displayed a higher amount of EDCs in their FF. In contrast, patients' residential area, source of food products, and nicotine or caffeine consumed were not associated with EDC accumulation. Clinicaltrials.gov NCT01385605 (11 July 2011).
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http://dx.doi.org/10.1007/s43032-021-00472-yDOI Listing
February 2021

Inhibition of Proinflammatory Cytokine Release by Flavones and Flavanones from the Leaves of Dracaena steudneri Engl.

Planta Med 2021 Mar 7;87(3):209-217. Epub 2020 Dec 7.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Dortmund, Germany.

The leaves of yielded 6 new flavonoids-3,5,7-trihydroxy-6-methyl-3',4'-methylenedioxyflavone (1: ), 5,7-dihydroxy-3-methoxy-6-methyl-3',4'-methylenedioxyflavone (2: ), 3,5,7-trihydroxy-6-methoxy-3',4'-methylenedioxyflavone (3: ), (2,3)-3,7-dihydroxy-6-methoxy-3',4'-methylenedioxyflavanone (4: ), 4',5,7-trihydroxy-3,3',8-trimethoxy-6-methylflavone (5: ), (2) 7-hydroxy-2',8-dimethoxyflavanone (6: )-together with 13 known congeners. Their structures were established using spectroscopic and spectrometric methods including NMR, CD, and HRMS measurements. The compounds were evaluated for their anti-inflammatory potential through measurement of the levels of cytokines IL-1, IL-2, GM-CSF, and TNF- in the supernatant of human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Flavones derivatives 1: -4: with a C-3'/4' methylenedioxy substituent led to a substantial increase in the production of IL-1 and GM-CSF out of 4 pro-inflammatory cytokines relative to LPS control. Quercetin derivatives 5, 11,: and 13: with a hydroxyl group at C-4' inhibited the production of IL-2, GM-CSF, and TNF-. The presence of a C-2/C-3 double bond in 14: was pivotal to the significantly stronger (0.4 to 27.5% of LPS control) inhibitory effect compared to its dihydro derivative 8: (36.2 to 262.7% of LPS control) against all tested cytokines. It is important to note that the inhibitory activity of 14: was substantially higher than that of the standard drug used, ibuprofen.
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http://dx.doi.org/10.1055/a-1306-1368DOI Listing
March 2021

Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury.

Cell Mol Gastroenterol Hepatol 2021 12;11(4):909-933. Epub 2020 Nov 12.

Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany. Electronic address:

Background & Aims: Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF.

Methods: To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK BioBank population-based cohort. For functional studies, male Nlrp6 mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF.

Results: Multivariate Cox regression analyses revealed a significantly increased risk (odds ratio, 2.3-3) for developing ALF in UK BioBank participants with PPI or ABx. Similarly, dysbiotic Nlrp6 mice displayed exacerbated APAP- and LPS-induced liver injury, which was linked to significantly reduced gut and liver tissue microbiota diversity and correlated with increased intestinal permeability at baseline. Fecal microbiota transfer (FMT) from Nlrp6 mice into wild-type (WT) mice augmented liver injury on APAP treatment in recipient WT mice, resembling the inflammatory phenotype of Nlrp6 mice. Specifically, FMT skewed monocyte polarization in WT mice toward a Ly6C inflammatory phenotype, suggesting a critical function of these cells as sensors of gut-derived signals orchestrating the inflammatory response.

Conclusions: Our data show an important yet unknown function of intestinal microbiota during ALF. Intestinal dysbiosis was transferrable to healthy WT mice via FMT and aggravated liver injury. Our study highlights intestinal microbiota as a targetable risk factor for ALF.
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http://dx.doi.org/10.1016/j.jcmgh.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900526PMC
November 2020

Stochastic dynamic mass spectrometric quantification of steroids in mixture - Part II.

Steroids 2020 12 15;164:108750. Epub 2020 Oct 15.

Lehrstuhl für Analytische Chemie, Institut für Umweltforschung, Fakultät für Chemie und Chemische Biologie, Universität Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Nordrhein-Westfalen, Germany.

This paper deals with quantification of the following steroids in mixture: hydrocortisone (1), deoxycorticosterone (2), progesterone (3) and methyltestosterone (4) by means of mass spectrometry and implementing our innovative stochatic dynamic functional relationship between the analyte concentration in solution and the experimental variable intensity. The mass spectrometric data are correlated independently using chromatography. Chemometric analysis is carried out.
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http://dx.doi.org/10.1016/j.steroids.2020.108750DOI Listing
December 2020

Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl.

Fitoterapia 2020 Oct 31;146:104717. Epub 2020 Aug 31.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany.

Four new steroidal sapogenins, dracaenogenins CF (1-4), a new conjugated chalcone-stilbene, 3''-methoxycochinchinenene H (5) together with eight known compounds namely, (25S)-spirosta-1,4-dien-3-one (6), trans-resveratrol (7), 4,4'-dihydroxy-3'-methoxychalcone (8), N-trans-coumaroyltyramine (9), N-trans-p-coumaroyloctopamine (10), N-trans-feruloyloctopamine (11), 7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-N,N-bis(4-hydroxyphenethyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxamide (12) and grossamide (13) were isolated from the stems of Dracaena usambarensis Engl. from Kenya. It is important to note that compounds 12 and 13 are being reported from this genus for the first time. Structural elucidation of the isolated compounds was done using spectroscopic (NMR, UV, IR, optical rotation) and spectrometric (HRESIMS) techniques. The absolute and relative configurations of the isolated compounds were determined by employing single crystal X-ray crystallography analysis, NOESY correlations and coupling constants. The anti-inflammatory potencies of the isolated compounds were evaluated by measuring the levels of four cytokines (IL-1β, IL-2, GM-CSF and TNF-α) in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At the tested concentration of 100 μM, the new conjugated chalcone-stilbene 5, the dihydrochalcone, 8 and the lignanamide, 13 were substantially more potent than the standard drug, ibuprofen, inhibiting the release of all the cytokines, IL-1β, IL-2, GM-CSF and TNF-α from 0.06-58.04% compared to LPS control. These compounds should therefore be considered for development into anti-inflammatory drug candidates. Compound 7 significantly decreased the release of GM-CSF (6.11% of LPS control) and TNF-α (18.35% of LPS control). The cytokine TNF-α was sensitive to all the tested compounds 1-13.
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http://dx.doi.org/10.1016/j.fitote.2020.104717DOI Listing
October 2020

Isoflavones from the seedpods of Tephrosia vogelii and pyrazoisopongaflavone with anti-inflammatory effects.

Fitoterapia 2020 Oct 1;146:104695. Epub 2020 Aug 1.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Str. 6, 44221 Dortmund, Germany. Electronic address:

Phytochemical investigation of Tephrosia vogelii seedpods led to the isolation of twelve compounds: vogelisoflavone A (1), vogelisoflavone B (2), isopongaflavone (3), onogenin, luteolin, 4',7-dihydroxy-3'-methoxyflavanone, trans-p-hydroxycinnamic acid, tephrosin, 2-methoxygliricidol, dehydrorotenone, 6a,12a-dehydro-α-toxicarol and pinoresinol. Compounds 1 and 2 are reported as new natural products. Isopongaflavone (3) was structurally modified using hydrazine to pyrazoisopongaflavone (4). These compounds were characterized based on their NMR and HRESIMS data. Further, four compounds (1-4) were evaluated for their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the compounds at a concentration of 100 μM suppressed the secretion of interleukin IL-1β interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α).
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http://dx.doi.org/10.1016/j.fitote.2020.104695DOI Listing
October 2020

Cytotoxic bufadienolides from the leaves of a medicinal plant Melianthus comosus collected in South Africa.

Bioorg Chem 2020 09 15;102:104102. Epub 2020 Jul 15.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Straße 6, 44227 Dortmund, Germany. Electronic address:

From the leaves of South African medicinal plant Melianthus comosus, four previously undescribed bufadienolides, 16β-formyloxymelianthugenin (1), 2β-acetoxymelianthusigenin (2), 2β-hydroxy-3β,5β-di-O-acetylhellebrigenin (3), and 2β-acetoxy-5β-O-acetylhellebrigenin (4) were isolated together with two known bufadienolides. The structural elucidation of the compounds was based on 1D and 2D NMR spectroscopy, high-resolution mass spectrometry, and other spectroscopic methods. The relative configurations were determined by single-crystal X-ray crystallography analysis and NOESY correlations. The isolated compounds displayed strong cytotoxicity against MCF-7 breast cancer cells, sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Compound 1 showed the most potent activity, with IC values of 0.07 μM towards CCRF-CEM, 0.06 μM towards CEM/ADR5000 and 0.36 μM towards MCF-7 followed by compound 4 with IC values of 0.13 μM towards CCRF-CEM, 0.08 μM towards CEM/ADR5000 and 0.53 μM towards MCF-7.
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http://dx.doi.org/10.1016/j.bioorg.2020.104102DOI Listing
September 2020

Anti-inflammatory norhopanes from the root bark of Fagaropsis angolensis (Engl.) H.M.Gardner.

Fitoterapia 2020 Oct 22;146:104690. Epub 2020 Jul 22.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany.

Two new norhopane derivatives namely 3β,6β,22-trihydroxy-7β,11α-di[(4-hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (1) and 3β,6β,22-trihydroxy-7β-[(4-hydroxybenzoyl)oxy]-21αH-24-norhopa-4(23)-ene (2) together with two previously reported compounds, including a norhopane, 3β,6β,11α-trihydroxy-7β-[(4-hydroxybenzoyl)oxy]-24-norhopa-4(23),17(21)-diene (3) and a norneohopane, (21αH)-24-norneohopa-4(23), 22(29)-diene-3β,6β,7β-triol 7-caffeate (4) were isolated from the root bark of Fagaropsis angolensis. Elucidation of their structures was achieved by spectroscopic (NMR, IR and UV) and spectrometric (HRESIMS) data and by comparison of these data with those of related compounds in the literature. Compounds 1-4 were evaluated for their anti-inflammatory activity by measuring the levels of cytokines, IL-1β, IL-2, GM-CSF and TNF-α in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC). All tested compounds decreased secretion of IL-1β and TNF-α. Compounds 2 and 4 caused significant decrease of the production of IL-2, GM-CSF and TNF-α compared to the reference drug, ibuprofen. These findings showed that the root barks of F. angolensis are rich source of norhopane derivatives and further provide a scientific rationale of using this plant in Kenyan folk medicine to relieve pain.
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http://dx.doi.org/10.1016/j.fitote.2020.104690DOI Listing
October 2020

Corrigendum to "Ozonation of rivaroxaban production waste water and comparison of generated transformation products with known in vivo and in vitro metabolites" [Sci. Total Environ. 714 (2020), 136825].

Sci Total Environ 2020 Nov 21;742:140865. Epub 2020 Jul 21.

Department of Technical Biochemistry, Technical University of Dortmund, Emil-Figge-Str. 66, 44227 Dortmund, Germany.

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http://dx.doi.org/10.1016/j.scitotenv.2020.140865DOI Listing
November 2020

Cytotoxic Bufadienolides from the Leaves of .

J Nat Prod 2020 07 14;83(7):2122-2128. Epub 2020 Jul 14.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.

is a medicinal plant endemic to South Africa. Its leaf extract led to the isolation of five new bufadienolides, 2β-acetoxy-3,5-di--acetylhellebrigenin (), 2β-acetoxy-3--acetylhellebrigenin (), 2β-acetoxy-14-deoxy-15β,16β-epoxymelianthugenin (), 2β-acetoxy-14-deoxy-15β,16β-epoxymelianthusigenin (), and 2β-hydroxymelianthusigenin (), and four known analogues. The structures of the compounds were elucidated using NMR and HRESIMS data analyses. The relative configurations were defined by single-crystal X-ray crystallography and NOESY correlations. The isolated compounds exhibited strong cytotoxicity against MCF-7 breast cancer cells and sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Compound showed the most potent activity, with IC values of 0.1 μM toward CCRF-CEM and CEM/ADR5000 and 0.3 μM toward MCF-7.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00060DOI Listing
July 2020

Synergistic anti-inflammatory activities of a new flavone and other flavonoids from vatke.

Nat Prod Res 2020 Mar 31:1-8. Epub 2020 Mar 31.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Dortmund, Germany.

A new flavone, named hildeflavone () along with 7 other known flavonoids were isolated from the aerial parts of Vatke. Their characterisation was based on NMR and MS data analysis. The anti-inflammatory properties of the crude extract, isolated compounds and combination of the compounds were investigated in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the isolated flavonoids at a concentration of 100 µM significantly reduced the production of interleukins (IL-1β, IL-2 and IL-6), interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α). It was also found that the combination of a flavone and flavanones exhibited remarkable synergistic anti-inflammatory effects on the production of the cytokines.
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http://dx.doi.org/10.1080/14786419.2020.1736065DOI Listing
March 2020

Anti-inflammatory Flavanones and Flavones from .

J Nat Prod 2020 04 10;83(4):996-1004. Epub 2020 Mar 10.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Strasse 6, 44221 Dortmund, Germany.

Phytochemical analysis of a methanol-dichloromethane (1:1) extract of the aerial parts of led to the isolation of 18 compounds. Seven of these, namely, lineaflavones A-D (-), 6-methoxygeraldone (), 8″-acetylobovatin (), and 5-hydroxy-7-methoxysaniculamin A () are new compounds. The compounds were characterized based on their NMR and HRMS data. The anti-inflammatory effects of the crude extract and isolated compounds were evaluated by measuring the levels of interleukins (IL-1β, IL-2, and IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). The crude extract inhibited the release of all cytokines except IL-1β, which slightly increased in comparison to the LPS control. All the tested compounds suppressed the production of IL-2, GM-CSF, and TNF-α. Whereas compounds , , -, -, , and decreased production of IL-6, compounds , , , , , -, and inhibited the release of IL-1β. It is worth noting that most of the compounds tested showed a superior reduction in cytokines release compared to the reference drug ibuprofen.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00922DOI Listing
April 2020

Ozonation of rivaroxaban production waste water and comparison of generated transformation products with known in vivo and in vitro metabolites.

Sci Total Environ 2020 Apr 21;714:136825. Epub 2020 Jan 21.

Department of Technical Biochemistry, Technical University of Dortmund, Emil-Figge-Str. 66, 44227 Dortmund, Germany.

During production of rivaroxaban, an orally administrated anticoagulant, process waste water is generated at several stages of manufacturing. Due to low biodegradability in conventional waste water treatment plants, it is currently incinerated. Thus, new pre-treatment methods for rivaroxaban-containing waste water could facilitate its subsequent biological processing. In this study, ozonation was investigated as the pre-treatment method, with special emphasis on the elimination of the target compound and the generation of its main transformation products. These were determined by high performance liquid chromatography - high resolution mass spectrometry (HPLC-HRMS). Our results show that the concentration of rivaroxaban in the ozonated waste water can be effectively reduced (below detection limit) under acidic conditions, whereas neutral or basic reaction environment proved less suitable. Four main transformation products were identified and their concentrations determined. Rivaroxaban and its most prominent transformation product acetoxamide were elucidated in multiple-stage mass spectrometry (MS) experiments. Transformation products derived from the degradation of rivaroxaban were then compared to its natural (animal and human) metabolites as well as other known derivatives. In contrast to previously published rivaroxaban-derived metabolites, the presented ozonation experiments resulted in new transformation products.
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http://dx.doi.org/10.1016/j.scitotenv.2020.136825DOI Listing
April 2020

MALDI-HRMS imaging and HPLC-HRESI-MS characterisation of kaurane diterpenes in the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae).

Phytochem Anal 2020 May 24;31(3):349-354. Epub 2019 Dec 24.

Chair of Environmental Chemistry and Analytical Chemistry, Department of Chemistry and Chemical Biology, Institute of Environmental Research (INFU), Dortmund, Germany.

Introduction: Kaurane diterpenes, notably xylopic acid, have demonstrated important biological activities including analgesia, anti-oxidant, antimicrobial and cytotoxicity. The fruits of Xylopia aethiopica have been reported to be a rich source of kaurane diterpenes.

Objective: An analytical approach for detailed imaging and characterisation of selected kaurane diterpenes was developed using matrix-assisted laser desorption/ionisation high-resolution mass spectrometry (MALDI-HRMS) imaging techniques and high-performance liquid chromatography-high resolution electrospray ionisation-tandem mass spectrometry (HPLC-HRESI-MS ) studies, respectively.

Methods: The images of the compounds were constructed based on selected ions from their HRESI-MS spectra. The matrix employed comprised a solution of α-cyano-4-hydroxycinnamic acid (HCCA) in acetonitrile-water with trifluoroacetic acid (TFA). HPLC-HRESI-MS measurements were conducted on an LTQ-Orbitrap spectrometer equipped with a heated electrospray ionisation (HESI)-II source.

Results: The analytical strategy adopted showed the spatial distribution of the compounds in the fruits of X. aethiopica based on the dominant ions at m/z 301.2163 [M + H - HOCOCH ] and m/z 399.1932 [M + K] for xylopic acid, m/z 317.2111 [M + H] and m/z 355.1670 [M + K] for 15-oxo-ent-kaur-16-en-19-oic acid and m/z 303.2319 [M + H] for ent-kaur-16-en-19-oic acid. The fragmentation patterns of the compounds were proposed based on the HRESI-MS measurements.

Conclusions: The study revealed the spatial variability, differential behaviours and specificity of the selected kaurane diterpenes in the fruit, seed and pericarp. The compounds under study were predominantly restricted to the pericarp of the fruit with trace amounts in the seed.
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http://dx.doi.org/10.1002/pca.2901DOI Listing
May 2020

A mass spectrometric stochastic dynamic diffusion approach to selective quantitative and 3D structural analyses of native cyclodextrins by electrospray ionization and atmospheric pressure chemical ionization methods.

Bioorg Chem 2019 12 20;93:103308. Epub 2019 Sep 20.

Lehrstuhl für Analytische Chemie, Institut für Umweltforschung, Fakultät für Chemie und Chemische Biologie, Universität Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Nordrhein-Westfalen, Germany.

The paper addressed shortcoming with highly precise and selective 3D structural analysis of native cyclodextrins in mixture using ions observable at low m/z-region by ESI- and APCI-mass spectrometry. Because of, the quantitative and structural analyses of CDs, in general, are vexed by a set of complications. The study outlines our own stochastic dynamic approaches to the latter issues based on new model relations, quantifing the measurable MS outcome intensity. They introduce the so-called stochastic dynamic mass spectrometric diffusion "D" parameter, exhibiting high accuracy, precision, sensitivity and selectivity, respectively. It is linearly connected with the so-called quantum chemical diffusion parameter "D" according to Arrhenius's theory. The most important upshot is that statistical parameters r = 0.99-0.99 has been obtained correlating between D and D parameters. Therefore, we determine high accurately 3D molecular and electronic structures of analytes by mass spectrometry. Fragment peaks at m/z 313, 279, 272, 252, 231, 214, 198, 171, 158 and 141 are examined. Mixtures of CDs and monomeric and acyclic oligomer carbohydrates glucose (1), sucrose (2), raffinose (3), melezitose (4) and cellotriose (5) are also studied. Our method is able to account precisely for the effect of the temperature under ESI- and APCI-MS conditions, as well. Correlative analysess between D parameters of ESI- and APCI-MS measurements under different temperatures is also shown. Chemometric tests are used. Another important results and conclusions, among others, to draw from this research are: (i) excellent linear correlation between D and D parameters of r = 0.99 is found looking at common ions at m/z 141, 158 and 171, belonging to 2-formyl-3,4-dihydroxy-pyranylium, 4,5,6-trihydroxy-6H-pyran-2-carbaldehyde and 3,4,5-trihydroxy-6-oxo-6H-pyran-2-ylmethylidyne-oxonium ions. Thus, we distinguish precisely between the last structure and 3-formyl-4,5-dihydroxy-2,7-dioxa-8-oxonia-bicyclo[4.2.0]octa-1(8),3,5-triene cation. In the case of ion at m/z 141 subtle electronic effects are distinguished between the mentioned structure and the charged 3,4-dihydroxy-6H-pyran-2-carbaldehyde one. The method determines precisely very similar structurally poly-OH-substituted derivatives. Because of, (ii) absolute reproducibility (r = 1) of D parameters of ESI-MS spectra is obtained studying the shown in point (i) MS peaks of β-CD between j and j numbers of experiments. The statistical equation is D = (0.51 ± 3.1.10) × D; (iii) the APCI- and ESI-MS provide identical results studying common MS ions of CDs and the correlation between D and D parameters excludes from error, due to, experiment; and (iv) The correlation between theory and experiment accounting for the factor temperature within our model equations shows r = 0.98 looking at the MS peaks at m/z 313 280, 279, 274 and 252, respectively. The effect of the temperature under both ESI- and APCI-MS conditions on the 3D molecular and electronic structures of CDs is precisely studied, respectively.
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http://dx.doi.org/10.1016/j.bioorg.2019.103308DOI Listing
December 2019

Metabolism and spatial distribution of metalaxyl in tomato plants grown under hydroponic conditions.

Chemosphere 2019 Mar 12;218:36-41. Epub 2018 Nov 12.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. Electronic address:

Knowledge about translocation of plant protection products (PPP's) in plants is important to understand the uptake via the root system. Here we report the combination of analysis of tissue extracts by LC-HRMS, autoradiography of C-labeled compounds and MALDI-MSI, which combine qualitative and quantitative information of chemical composition and the spatial distribution of PPP's and their metabolites in situ. Therefore, the uptake of the phenylamide fungicide metalaxyl was studied in tomato plants (Solanum lycopersicum) using a hydroponic system. The plants have been cultivated in perlite until the two-leaf stage and were transferred into the hydroponic test system afterwards. The radioactive labeled fungicide was readily taken up by the roots during the normal water consumption and radioactivity was translocated uniformly to the aboveground part of the tomato plants, while only small proportion of the applied radioactivity were observed in the roots. The distribution of metalaxyl after the plant uptake experiment in the primary roots where analyzed by a transversal tissue section in the zone of maturation. Metalaxyl is mainly localized in root xylem and in cortex located at the epidermis. With LC-HRMS and radiochemical analyses of stem and leaf, no parent compound was detectable. Four polar metabolites were the main identified components of the residue and could be visualized by MALDI-imaging mass spectrometry. With these results we could show, that the fungicide metalaxyl is taken up by the plant via the roots during the regular water consumption and transported to xylem.
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http://dx.doi.org/10.1016/j.chemosphere.2018.11.069DOI Listing
March 2019

Stable Isotope Labeling of Prodiginines and Serratamolides Produced by Serratia marcescens Directly on Agar and Simultaneous Visualization by Matrix-Assisted Laser Desorption/Ionization Imaging High-Resolution Mass Spectrometry.

Anal Chem 2018 11 5;90(22):13167-13172. Epub 2018 Nov 5.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry , TU Dortmund , Otto-Hahn-Straße 6 , 44221 Dortmund , Germany.

Matrix-assisted laser desorption/ionization imaging high-resolution mass spectrometry (MALDI-imaging-HRMS) is an important technique for visualizing the spatial distribution of compounds directly on the surface of organisms such as microorganisms, insects, plants, animals, and human tissues. However, MALDI-imaging-HRMS and the stable isotope labeling approach have never been combined for the detection and simultaneous visualization of labeled and unlabeled compounds, their analogues and derivatives, as well as their precursors. Herein, we present a methodology that labels microbial secondary metabolites directly on agar with stable isotopes and allows concurrent spatial distribution analyses by MALDI-imaging-HRMS. Using a thin film of labeled agar supplemented with [1-C]-l-proline, [methyl-D]-l-methionine, NHCl, or [N]-l-serine overlaid on unlabeled agar, we demonstrate the incorporation of labeled precursors into prodiginines and serratamolides produced by an endophytic bacterium, Serratia marcescens, by MALDI-imaging-HRMS and HPLC-HRMS. Further, we show the incorporation of CD into prodigiosin as well as its characteristic fragments directly by MALDI-imaging-HRMS. Our methodology has several advantages over currently existing techniques. First, both labeled and unlabeled compounds can be visualized simultaneously in high spatial resolution along with their labeled and unlabeled precursors. Second, by using a thin film of labeled agar, we utilize minimum amounts of expensive labeled compounds (1-3 mg) ensuring a cost-effective method for investigating biosynthetic pathways. Finally, our method allows in situ visualization and identification of target and nontarget compounds without the need of isolating the compounds. This is important for compounds that are produced by microorganisms in low, physiologically, or ecologically relevant concentrations.
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http://dx.doi.org/10.1021/acs.analchem.8b03633DOI Listing
November 2018

Cardenolides and dihydro-β-agarofuran sesquiterpenes from the seeds of Salacia staudtiana.

Fitoterapia 2018 Nov 21;131:174-181. Epub 2018 Oct 21.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. Electronic address:

Phytochemical studies of the seeds of the Cameroonian medicinal plant, Salacia staudtiana, resulted in the isolation and identification of five new cardenolides (1-5) as well as a new dihydro-β-agarofuran (9), along with eight known compounds. The structures of all compounds were elucidated by 1D/2D NMR, ESI-HRMS data and comparison with literature data. The relative configurations of the new compounds were defined by X-ray crystallography analysis, NOESY correlations and coupling constants. We evaluated their antibacterial efficacy against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, and two pathogenic strains of Staphylococcus aureus and Pseudomonas aeruginosa, compared to the standard antibiotics, streptomycin and gentamicin. Moreover, we assessed the antibacterial activity of the crude extract of the seeds in parallel to evaluate the plausible synergistic effects of the compounds in chemical defense of the seeds during germination and plant reproduction. The isolated compounds showed moderate antibacterial activities against the tested organisms. Compounds 1 and 3 and the crude extract exhibited distinct antibacterial activities against B. subtilis and S. aureus. The isolated compounds showed weak DPPH radical scavenging properties compared to the reference standard (Trolox). Our study lends evidence to the antibacterial chemical defense of S. staudtiana seeds by seed-borne compounds.
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http://dx.doi.org/10.1016/j.fitote.2018.10.025DOI Listing
November 2018

Bile Microinfarcts in Cholestasis Are Initiated by Rupture of the Apical Hepatocyte Membrane and Cause Shunting of Bile to Sinusoidal Blood.

Hepatology 2019 02 19;69(2):666-683. Epub 2018 Nov 19.

Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.

Bile duct ligation (BDL) is an experimental procedure that mimics obstructive cholestatic disease. One of the early consequences of BDL in rodents is the appearance of so-called bile infarcts that correspond to Charcot-Gombault necrosis in human cholestasis. The mechanisms causing bile infarcts and their pathophysiological relevance are unclear. Therefore, intravital two photon-based imaging of BDL mice was performed with fluorescent bile salts (BS) and non-BS organic anion analogues. Key findings were followed up by matrix-assisted laser desorption ionization imaging, clinical chemistry, immunostaining, and gene expression analyses. In the acute phase, 1-3 days after BDL, BS concentrations in bile increased and single-cell bile microinfarcts occurred in dispersed hepatocytes throughout the liver caused by the rupture of the apical hepatocyte membrane. This rupture occurred after loss of mitochondrial membrane potential, followed by entry of bile, cell death, and a "domino effect" of further death events of neighboring hepatocytes. Bile infarcts provided a trans-epithelial shunt between bile canaliculi and sinusoids by which bile constituents leaked into blood. In the chronic phase, ≥21 days after BDL, uptake of BS tracers at the sinusoidal hepatocyte membrane was reduced. This contributes to elevated concentrations of BS in blood and decreased concentrations in the biliary tract. Conclusion: Bile microinfarcts occur in the acute phase after BDL in a limited number of dispersed hepatocytes followed by larger infarcts involving neighboring hepatocytes, and they allow leakage of bile from the BS-overloaded biliary tract into blood, thereby protecting the liver from BS toxicity; in the chronic phase after BDL, reduced sinusoidal BS uptake is a dominant protective factor, and the kidney contributes to the elimination of BS until cholemic nephropathy sets in.
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http://dx.doi.org/10.1002/hep.30213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587841PMC
February 2019

Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI.

Arch Toxicol 2018 09 23;92(9):2963-2977. Epub 2018 Jul 23.

Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.

Acetaminophen (APAP) is one of the most intensively studied compounds that causes hepatotoxicity in the pericentral region of the liver lobules. However, spatio-temporal information on the distribution of APAP, its metabolites and GSH adducts in the liver tissue is not yet available. Here, we addressed the question, whether APAP-GSH adducts and GSH depletion show a zonated pattern and whether the distribution of APAP and its glucuronide as well as sulfate conjugates in liver lobules are zonated. For this purpose, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) technique was established, where the MSI images were superimposed onto CYP2E1 immunostained tissue. A time-dependent analysis (5, 15, 30, 60, 120, 240, 480 min) after intraperitoneal administration of 300 mg/kg APAP and a dose-dependent analysis (56 up to 500 mg APAP/kg) at 30 min were performed. The results demonstrate that the MALDI MSI technique allows the assignment of compounds and their metabolites to specific lobular zones. APAP-GSH adducts and GSH depletion occurred predominantly in the CYP2E1-positive zone of the liver, although GSH also decreased in the periportal region. In contrast, the parent compound, APAP sulfate and APAP glucuronide did not show a zonated pattern and tissue concentrations showed a similar time course as the corresponding analyses were performed with blood from the portal and liver veins. In conclusion, the present study is in agreement with the concept that pericentral CYPs form NAPQI that in the same cell binds to and depletes GSH but a lower level of GSH adducts is also observed in the periportal region. The results also provide further evidence of the recently published concept of 'aggravated loss of clearance capacity' according to which also liver tissue that survives intoxication may transiently show decreased metabolic capacity.
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http://dx.doi.org/10.1007/s00204-018-2271-3DOI Listing
September 2018

Cardenolides from the stem bark of Salacia staudtiana.

Fitoterapia 2018 Jun 9;127:402-409. Epub 2018 Apr 9.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. Electronic address:

Seven new cardenolides, staudtianoside A-F (1-6) and staudtianogenin A (8), were isolated along with six known compounds from the stem bark of the Cameroonian medicinal plant Salacia staudtiana Loes. ex Fritsch. The structures were elucidated by means of ESI-HRMS and NMR spectroscopic methods and by comparison with literature data. The relative configurations of the new compounds were determined by X-ray diffraction analysis, NOESY correlation and coupling constants. We evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, as well as against two human pathogenic clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa. Compounds 1, 2 and 8 exhibited marked antibacterial potencies against the clinically relevant P. aeruginosa that were comparable to the standard antibiotics. Compound 2 was also active against S. aureus and E. coli. Further, compounds 5 and 8 demonstrated efficacy against E. coli as well as B. subtilis. The structure-activity relationship of the tested compounds is discussed.
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http://dx.doi.org/10.1016/j.fitote.2018.04.008DOI Listing
June 2018

Spatial-temporal profiling of prodiginines and serratamolides produced by endophytic Serratia marcescens harbored in Maytenus serrata.

Sci Rep 2018 03 27;8(1):5283. Epub 2018 Mar 27.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221, Dortmund, Germany.

An endophytic bacterium, Serratia marcescens MSRBB2, isolated from inner bark of a Cameroonian Maytenus serrata plant, was subjected to the OSMAC (One Strain Many Compounds) approach and metabolic profiling using HPLC-HRMS. We identified 7 prodiginines along with 26 serratamolides. Their biosynthetic pathways were elucidated by feeding with labeled precursors in combination with HRMS. Dual-culture confrontation/restriction assays of the bacterial endophyte were devised with coexisting fungal endophytes (Pestalotiopsis virgatula, Aspergillus caesiellus and Pichia spp.) as well as with unrelated, non-endophytic fungi belonging to the same genera. The assays were combined with scanning electron microscopy (SEM) as well as matrix-assisted laser desorption ionization imaging high-resolution mass spectrometry (MALDI-imaging-HRMS) for visualizing, both in high spatial and temporal resolution, the distribution and interplay of the compounds during microbial interactions. We demonstrated the effect of prodigiosin produced by endophytic S. marcescens MSRBB2 as an allelochemical that specifically inhibits coexisting endophytic fungi. Our results provide new insights into the physiological and ecological relevance of prodiginines and serratamolides within the context of allelopathy and chemical defense interaction occurring between coexisting endophytes harbored in M. serrata.
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http://dx.doi.org/10.1038/s41598-018-23538-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869619PMC
March 2018

Localization and Organization of Scopolamine Biosynthesis in Duboisia myoporoides R. Br.

Plant Cell Physiol 2018 Jan;59(1):107-118

Technical Biochemistry, Department of Biochemical and Chemical Engineering, Technical University Dortmund, D-44227 Dortmund, Germany.

Tropane alkaloids (TAs), especially hyoscyamine and scopolamine, are important precursors for anticholinergic and antispasmodic drugs. Hyoscyamine and scopolamine are currently obtained at commercial scale from hybrid crosses of Duboisia myoporoides × Duboisia leichhardtii plants. In this study, we present a global investigation of the localization and organization of TA biosynthesis in a Duboisia myoporoides R. Br. wild-type line. The tissue-specific spatial distribution of TAs within D. myoporoides is presented, including quantification of the TAs littorine, 6-hydroxy hyoscyamine, hyoscyamine, scopolamine and, additionally, hyoscyamine aldehyde as well as scopolamine glucoside. Scopolamine (14.77 ± 5.03 mg g-1), and to a lesser extent hyoscyamine (3.01 ± 1.54 mg g-1) as well as 6-hydroxy hyoscyamine (4.35 ± 1.18 mg g-1), are accumulated in leaves during plant development, with the highest concentration of total TAs detected in 6-month-old plants. Littorine, an early precursor in TA biosynthesis, was present only in the roots (0.46 ± 0.07 mg g-1). During development, the spatial distribution of all investigated alkaloids changed due to secondary growth in the roots. Transcripts of pmt, tr-I and cyp80f1 genes, involved in early stages of TA biosynthesis, were found to be most abundant in the roots. In contrast, the transcript encoding hyoscyamine 6β-hydroxylase (h6h) was highest in the leaves of 3-month-old plants. This investigation presents the spatial distribution of biochemical components as well as gene expression profiles of genetic factors known to participate in TA biosynthesis in D. myoporoides. The results of this investigation may aid in future breeding or genetic enhancement strategies aimed at increasing the yields of TAs in these medicinally valuable plant species.
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http://dx.doi.org/10.1093/pcp/pcx165DOI Listing
January 2018

seco-Tiaminic acids B and C: Identification of two novel 3,4-seco-tirucallane triterpenoids isolated from the root of Entandrophragma congoënse (Meliaceae).

Fitoterapia 2018 Jan 5;124:17-22. Epub 2017 Oct 5.

Department of Chemistry, Higher Teachers' Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon. Electronic address:

Chemical investigation of the roots of Entandrophragma congoënse (Meliaceae) led to the isolation of two new 3,4-seco-tirucallane triterpenes, namely seco-tiaminic acids B and C (1 and 2) together with nine known compounds: 3,4-secotirucalla-21-formyl-23-oxo-4(28),7,24-trien-3-oic acid (3), methyl angolensate (4), molucensin N (5), molucensin O (6), piscidinol A (7), 7α,20(S)-dihydroxy-4,24(28)-ergostadien-3-one (8), 24-methylene-cholest-5-en-3β,7α-diol (9), entilin A (10), and entilin B (11). Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, HRMS, and CD analyses; new results were compared to existing data in the literature. The two newly identified seco-tiaminic acids showed moderate antiplasmodial and cytotoxic activities against a chloroquine-sensitive strain of the malaria parasite (Plasmodium falciparum NF54) and were cytotoxic toward an L6 rat skeletal myoblast cell line, respectively.
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http://dx.doi.org/10.1016/j.fitote.2017.10.004DOI Listing
January 2018

Ozone pretreatment of process waste water generated in course of fluoroquinolone production.

Chemosphere 2017 Oct 12;185:953-963. Epub 2017 Jul 12.

Department of Technical Biochemistry, Technical University of Dortmund, Emil-Figge-Str. 66, 44227 Dortmund, Germany. Electronic address:

During production of active pharmaceutical ingredients, process waste water is generated at several stages of manufacturing. Whenever possible, the resulting waste water will be processed by conventional waste water treatment plants. Currently, incineration of the process waste water is the method to eliminate compounds with high biological activity. Thus, ozone treatment followed by biological waste water treatment was tested as an alternative method. Two prominent representatives of the large group of fluoroquinolone antibiotics (ciprofloxacin and moxifloxacin) were investigated, focussing on waste water of the bulk production. Elimination of the target compounds and generation of their main transformation products were determined by liquid chromatography - high resolution mass spectrometry (LC-HRMS). The obtained results demonstrated, that the concentration of moxifloxacin and its metabolites can be effectively reduced (>99.7%) prior entering the receiving water. On the contrary, the concentration of ciprofloxacin and its metabolites remained too high for safe discharge, necessitating application of prolonged ozonation for its further degradation. The required ozonation time can be estimated based on the determined kinetics. To assure a low biological activity the ecotoxicity of the ozonated waste water was investigated using three trophic levels. By means of multiple-stage mass spectrometry (MS) experiments several new transformation products of the fluoroquinolones were identified. Thus, previously published proposed structures could be corrected or confirmed.
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http://dx.doi.org/10.1016/j.chemosphere.2017.07.040DOI Listing
October 2017

Chemometric evaluation of hypericin and related phytochemicals in 17 in vitro cultured Hypericum species, hairy root cultures and hairy root-derived transgenic plants.

J Pharm Pharmacol 2019 Jan 19;71(1):46-57. Epub 2017 Jul 19.

Department of Genetics, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, Košice, Slovakia.

Objectives: The objective of this study was to ascertain the presence and correlations among eight important secondary metabolites viz. hypericin, pseudohypericin, emodin, hyperforin, rutin, hyperoside, quercetin and quercitrin in different organs of 17 in vitro cultured Hypericum species, along with H. tomentosum and H. tetrapterum hairy root cultures, and hairy root-derived transgenic plants of H. tomentosum.

Methods: Samples were extracted and analysed by LC-MS. The LC-MS data were subjected to chemometric evaluations for metabolite profiling and correlating the phytochemical compositions in different samples.

Key Findings: Hypericin, pseudohypericin and their proposed precursor emodin were detected in various levels in the leaves of eight Hypericum species. The highest content of hypericins and emodin was found in H. tetrapterum, which contains the studied secondary metabolites in all plant organs. A significant positive correlation between hypericins and emodin was observed both by principal component analysis (PCA) and multidimensional scaling (MDS), indicating the role of emodin as a possible precursor in the biosynthetic pathway of hypericins. Flavonoids were found in all tested plant organs except roots of H. pulchrum. The hairy roots lacked hypericin, pseudohypericin, emodin, hyperforin and rutin. However, the hairy root-derived transgenic plants showed a significant increase in flavonoids.

Conclusions: This study broadens knowledge about the phytochemical composition of selected in vitro cultured Hypericum species, compared to that of hairy root cultures and hairy root-derived transgenic plants.
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http://dx.doi.org/10.1111/jphp.12782DOI Listing
January 2019

Antibacterial secondary metabolites from an endophytic fungus, Fusarium solani JK10.

Fitoterapia 2017 Jun 6;119:108-114. Epub 2017 Apr 6.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. Electronic address:

Extensive chemical investigation of the endophytic fungus, Fusarium solani JK10, harbored in the root of the Ghanaian medicinal plant Chlorophora regia, using the OSMAC (One Strain Many Compounds) approach resulted in the isolation of seven new 7-desmethyl fusarin C derivatives (1-7), together with five known compounds (8-12). The structures of the new compounds were elucidated by analysis of their spectroscopic data including 1D, 2D NMR, HRESI-MS and IR data. The relative configuration of compounds 1/2 was deduced by comparison of their experimental electronic circular dichroism (ECD) and optical rotation data with those reported in literature. The absolute configuration of solaniol (10), a known compound with undefined absolute stereochemistry, was established for the first time by X-ray diffraction analysis of a single-crystal structure using Cu-Kα radiation. The antibacterial activities of the crude fungal extract and the compounds isolated from the fungus were evaluated against some clinically important bacterial strains such as Staphylococcus aureus and Bacillus subtilis, as well as an environmental strain of Escherichia coli and the soil bacterium Acinetobacter sp. BD4. Compounds 3/4 and 6 exhibited antibacterial efficacies against the soil bacterium Acinetobacter sp., comparable to the reference standard streptomycin. All the tested compounds (1-9) demonstrated antibacterial activity against the environmental strain of E. coli, whereas no antibacterial activity was observed against S. aureus and B. subtilis. The antibacterial activity of the isolated compounds typically against E. coli and Acinetobacter sp. provides further insight into the possible involvement of root-borne endophytes in chemical defense of their host plants in selected ecological niches.
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http://dx.doi.org/10.1016/j.fitote.2017.04.007DOI Listing
June 2017

Spatial profiling of maytansine during the germination process of Maytenus senegalensis seeds.

Fitoterapia 2017 Jun 3;119:51-56. Epub 2017 Apr 3.

Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, Otto-Hahn-Straße 6, 44221 Dortmund, Germany. Electronic address:

The ecological role of maytansine, an important antineoplastic and antimicrobial compound with high cytotoxicity, particularly as a chemical defense compound has remained elusive since its discovery in the 1970s in Maytenus and Putterlickia plants. In the present study, we have used MALDI-imaging-HRMS to visualize the occurrence as well as spatial and temporal distribution of maytansine in a Maytenus senegalensis plant, seeds obtained from the mother plant during seeding stage, through the germination of the seeds, and finally up to the establishment of seedlings (or daughter plants). Although the mother plant was devoid of maytansine, the bioactive compound was found to be distributed in the cotyledons and the endosperm of the seeds with an augmented accretion towards the seed coat. Furthermore, maytansine was always detected in the emerging seedlings, particularly the cortex encompassing the radicle, hypocotyl, and epicotyl. The typical pattern of accumulation of maytansine not only in the seeds but also during germination provides a proof-of-concept that M. senegalensis is ecologically primed to trigger the production of maytansine in vulnerable tissues such as seeds during plant reproduction. By utilizing maytansine as chemical defense compound against predators and/or pathogens, the plant can ensure viability of the seeds and successful germination, thus leading to the next generation of daughter plants.
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http://dx.doi.org/10.1016/j.fitote.2017.03.014DOI Listing
June 2017