1. A Three-step Process to Isolate Large Quantities of Bioactive Sesquiterpene Lactones from Cichorium intybus L. Roots and Semi-synthesis of Chicory STLs Standards
- Author
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Francesca Ruggieri, Philippe Hance, Bruna Gioia, Alexandre Biela, Pascal Roussel, Jean-Louis Hilbert, Nicolas Willand, Université de Lille, CNRS, Centrale Lille, ENSCL, Univ. Artois, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 [M2SV], Transfrontalière BioEcoAgro - UMR 1158 [BioEcoAgro], Médicaments et Molécules pour agir sur les Systèmes Vivants (M2SV) - U1177, Unité de Catalyse et Chimie du Solide (UCCS) - UMR 8181, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-20-PAMR-0005,Mustart,Multiparametric Strategies against Antibiotic Resistance in Tuberculosis(2020), and European Project: 847568,H2020,H2020-MSCA-COFUND-2018,PEARL(2019)
- Subjects
chicory ,sesquiterpene lactones ,13-dihydrolactucin ,lactucin ,plant extraction ,semisynthesis of analytical standards ,Pharmaceutical Science ,medicinal_chemistry_50 ,[CHIM.INOR]Chemical Sciences/Inorganic chemistry ,Drug Discovery ,Molecular Medicine ,11,13-dihydrolactucin - Abstract
Sesquiterpene lactones (STLs) are a large group of terpenoids most commonly found in plants of the Asteraceae family, e.g., in chicory plants, displaying a wide range of interesting biological activities. However, further studies on the biological potential of chicory-derived STLs and analogues are challenging as only four of these molecules are commercially available (as analytical standards), and to date, there are no published or patented simple extraction–purification processes capable of large-scale STLs isolation. In this work, we describe a novel three-step large-scale extraction and purification method for the simultaneous purification of 11,13-dihydrolactucin (DHLc) and lactucin (Lc) starting from a chicory genotype rich in these STLs and the corresponding glucosyl and oxalyl conjugated forms. After a small-scale screening on 100 mg of freeze-dried chicory root powder, the best results were achieved with a 17 h water maceration at 30 °C. With these conditions, we managed to increase the content of DHLc and Lc, at the same time favoring the hydrolysis of their conjugated forms. On a larger scale, the extraction of 750 g of freeze-dried chicory root powder, followed by a liquid–liquid extraction step and a reversed-phase chromatography, allowed the recovery of 642.3 ± 76.3 mg of DHLc and 175.3 ± 32.9 mg of Lc. The two pure STLs were subsequently used in the context of semisynthesis to generate analogues for biological evaluation as antibacterial agents. In addition, other described chicory STLs that are not commercially available were also synthesized or extracted to serve as analytical standards for the study. In particular, lactucin-oxalate and 11,13-dihydrolactucin-oxalate were synthesized in two steps starting from Lc and DHLc, respectively. On the other hand, 11β,13-dihydrolactucin-glucoside was obtained after a MeOH/H2O (70/30) extraction, followed by a liquid–liquid extraction step and a reversed-phase chromatography. Together, this work will help facilitate the evaluation of the biological potential of chicory-derived STLs and their semisynthetic analogues.
- Published
- 2023
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