Lignans and sesquiterpene lactones from Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae)

  • Phytochemistry. 2019 Sep;165:112047. doi: 10.1016/j.phytochem.2019.05.020.
Oleksandr Shulha  1 ,  Serhat Sezai Çiçek  1 ,  Helle Wangensteen  2 ,  Janina Kroes  3 ,  Malte Mäder  4 ,  Ulrich Girreser  4 ,  Jandirk Sendker  5 ,  Karin Jöhrer  6 ,  Richard Greil  7 ,  Wolfgang Schühly  8 ,  Alfonso Mangoni  9 ,  Laura Grauso  10 ,  Christoph van Thriel  3 ,  Christian Zidorn  11
Affiliations
  • 1. Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118, Kiel, Germany.
  • 2. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068, 0316, Oslo, Norway.
  • 3. Leibniz-Institut für Arbeitsforschung, TU Dortmund, Ardeystraße 67, 44139, Dortmund, Germany.
  • 4. Pharmazeutisches Institut, Abteilung Pharmazeutische Chemie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118, Kiel, Germany.
  • 5. Institut für Pharmazeutische Biologie und Phytochemie, Universiät Münster, Corrensstraße 48, 48149, Münster, Germany.
  • 6. Tyrolean Cancer Research Institute, Innrain 66, 6020, Innsbruck, Austria.
  • 7. Tyrolean Cancer Research Institute, Innrain 66, 6020, Innsbruck, Austria; Paracelsus Medical University Salzburg, Department of Internal Medicine III, Laboratory for Immunological and Molecular Cancer Research, Müllner Hauptstraße 48, 5020, Salzburg, Austria.
  • 8. Institut für Zoologie, Universität Graz, Universitätsplatz 2/I, 8010, Graz, Austria.
  • 9. Dipartimento di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, 80131, Napoli, Italy.
  • 10. Dipartimento di Agraria, Università di Napoli Federico II, Via Università 100, 80055, Portici (NA), Italy.
  • 11. Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118, Kiel, Germany. Electronic address: [email protected].
PMID: 31203102 DOI: 10.1016/j.phytochem.2019.05.020
Abstract

Four undescribed Lignans and two undescribed sesquiterpenic acids, together with three known compounds (hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The Lignans were identified as 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranosyl-2'-O-methacrylate, (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one, and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid were determined using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100 mM against MM1S strain. No neurotoxicity was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside, hypochoeroside C, hypochoeroside D, and hypochoerosidic acid D were quantified in unstressed and drought-stressed Plants using HPLC-DAD. Drought-stressed Plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-β-D-glucopyranoside and sesquiterpene lactone hypochoeroside C.

Keywords
Botanical systematics; Cytotoxicity; Hypochaeris radicata subsp. neapolitana, Asteraceae; Neurotoxicity; Phenylpropanoids; Sesquiterpenoids; Stringhalt.
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