Добірка наукової літератури з теми "Dihydrolactucine"

Two new sesquiterpene lactones (guaianolides), 15-hydroxytaraxacin (1) and 6,8,11-epi-desacetylmatricarin (2), along with three known compounds, desacetylmatricarin (3), 11β ,13-dihydrolactucin (4), and 11β ,13-dihydrolactucopicrin (5), were isolated from the aerial parts of Cichorium intybus L.

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.

Free and glycosylated sesquiterpene lactones (SLs), which are abundant in leafy vegetables including Brussels/witloof chicory, possess health-promoting effects in vivo. However, the pharmacokinetics of dietary source of SLs remain largely unknown. In this open-label and single-dose trial, sixteen healthy volunteers consumed 150 g of Brussels/witloof chicory juice containing 48.77 μmol SLs in 5 min. Blood, urine, and fecal samples were collected before and after chicory consumption in 24 h. No SLs were detected in the serum, urine, and fecal samples before chicory consumption in all of the participants. Chicory consumption increased lactucin, 11β,13-dihydrolactucin, and their glucuronide/sulfate conjugates, rather than lactucopicrin and 11β,13-dihydrolactucopicrin, as well as glycosylated SLs in biological samples. The peak concentration of total SLs in serum reached 284.46 nmol/L at 1 h, while, in urine, this peak was 220.3 nmol between 2 and 6 h. The recovery of total SLs in blood, urine, and feces was 7.03%, 1.13%, and 43.76% of the ingested dose, respectively. Human fecal suspensions with intestinal microbiota degraded glycosylated SLs in chicory, and converted lactucopicrin and 11β,13-dihydrolactucopicrin to lactucin and 11β,13-dihydrolactucin, respectively. Collectively, Brussels/witloof chicory SLs are poorly bioavailable and they undergo partial gut microbial and phase II metabolism in humans.

The aerial parts of <i>Picris pauciflora</i> Willd. (<i>Asteraceae</i>) yielded 11β, 13-dihydrolactucin, while the roots of the plant afforded 3-β-D-glucopyranosides of 11β, 13-dihydrozaluzanin C and 9α-hydroxy-11β, 13-dihydrozaluzanin C (ixerin F). The guaianolides were isolated from ethanol extracts using chromatographic methods and were identified on the basis of spectral analysis. They are reported for the first time from this species.

Cichorium intybus L. has recently gained major attention due to large quantities of health-promoting compounds in its roots, such as inulin and sesquiterpene lactones (SLs). Chicory is the main dietary source of SLs, which have underexplored bioactive potential. In this study, we assessed the capacity of SLs to permeate the intestinal barrier to become physiologically available, using in silico predictions and in vitro studies with the well-established cell model of the human intestinal mucosa (differentiated Caco-2 cells). The potential of SLs to modulate inflammatory responses through modulation of the nuclear factor of activated T-cells (NFAT) pathway was also evaluated, using a yeast reporter system. Lactucopicrin was revealed as the most permeable chicory SL in the intestinal barrier model, but it had low anti-inflammatory potential. The SL with the highest anti-inflammatory potential was 11β,13-dihydrolactucin, which inhibited up to 54% of Calcineurin-responsive zinc finger (Crz1) activation, concomitantly with the impairment of the nuclear accumulation of Crz1, the yeast orthologue of human NFAT.

Lactuca L. species belong to the Asteraceae family and these plants are traditionally used for therapeutic purposes around the world. The dried milky latex of L. serriola is known as “lettuce oil” and is used as a sedative in Turkey. This study aimed to evaluate the sedative effects and analyze the chemical compositions of latexes obtained from some Lactuca species growing in Turkey. The sedative effects were evaluated through various behavioral tests on mice. For this purpose, latexes were obtained from L. glareosa Boiss., L. viminea (L.) J. Presl and C. P, L. mulgedioides (Vis and Panćić) Boiss. and Kotschy ex. Boiss., L. saligna L., and L. serriola L. The latex from L. saligna showed the highest sedative effects, whilst L. serriola and L. viminea latexes also displayed significant sedative effects compared to the control group at a dose of 100 mg/kg. However, the latexes from L. glareosa and L. mulqedioides did not exhibit any sedative effects on mice. Characteristic sesquiterpene lactones (lactucin, lactucopicrin, 11,13β-dihydrolactucin, and 11,13β-dihydrolactucopicrin) were determined qualitatively and quantitatively by high-performance liquid chromatography (HPLC). Lactucin was identified as the main component.

Cicerbita alpina (L.) Wallr. is a perennial herbaceous plant in the tribe Cichorieae (Lactuceae), Asteraceae family, distributed in the mountainous regions in Europe. In this study, we focused on the metabolite profiling and the bioactivity of C. alpina leaves and flowering heads methanol-aqueous extracts. The antioxidant activity of extracts, as well as inhibitory potential towards selected enzymes, involving in several human diseases, including metabolic syndrome (α-glucosidase, α-amylase, and lipase), Alzheimer’s disease, (cholinesterases: AChE, BchE), hyperpigmentation (tyrosinase), and cytotoxicity were assessed. The workflow comprised ultra-high-performance liquid chromatography—high-resolution mass spectrometry (UHPLC-HRMS). UHPLC-HRMS analysis revealed more than 100 secondary metabolites, including acylquinic, acyltartaric acids, flavonoids, bitter sesquiterpene lactones (STLs), such as lactucin, dihydrolactucin, their derivatives, and coumarins. Leaves showed a stronger antioxidant activity compared to flowering heads, as well as lipase (4.75 ± 0.21 mg OE/g), AchE (1.98 ± 0.02 mg GALAE/g), BchE (0.74 ± 0.06 mg GALAE/g), and tyrosinase (49.87 ± 3.19 mg KAE/g) inhibitory potential. Flowering heads showed the highest activity against α-glucosidase (1.05 ± 0.17 mmol ACAE/g) and α-amylase (0.47 ± 0.03). The obtained results highlighted C. alpina as a rich source of acylquinic, acyltartaric acids, flavonoids, and STLs with significant bioactivity, and therefore the taxon could be considered as a potential candidate for the development of health-promoting applications.

The composition of menus and the sequence of foodstuffs consumed during a meal underlies elaborate rules. However, the molecular foundations for the observed taste- and pleasure-raising effects of complex menus are obscure. The molecular identification and characterization of taste receptors can help to gain insight into the complex interrelationships of food items and beverages during meals. In our study, we quantified important bitter compounds in chicory and chicory-based surrogate coffee and used them to identify responsive bitter taste receptors. The two receptors, TAS2R43 and TAS2R46, are exquisitely sensitive to lactucin, lactucopicrin, and 11β,13-dihydrolactucin. Sensory testing demonstrated a profound influence of the sequence of consumption of chicory, surrogate coffee, and roasted coffee on the perceived bitterness by human volunteers. These findings pave the way for a molecular understanding of some of the mixture effects underlying empirical meal compositions.

Les produits naturels (PNs) ont perdu en popularité depuis l'introduction des petites molécules synthétiques il y a plusieurs années. De nombreuses raisons expliquent ce choix, telles que les difficultés d'accès et d'approvisionnement, la complexité de la chimie des PNs et l'avènement de la chimie combinatoire. Cependant, les PNs offrent de nombreuses propriétés intéressantes par rapport aux molécules synthétiques conventionnelles, ce qui leur confère à la fois des avantages et des inconvénients dans le contexte de la recherche de principes actifs. En général, les PNs se caractérisent par un plus grand nombre de carbones sp3 et de centres stéréogènes, une grande diversité de squelettes et une grande complexité structurelle. La moitié des médicaments approuvés par la FDA depuis 1994 étant des PNs ou des dérivés hémisynthétiques, et étant donnée la récente stagnation de la recherche et du développement de nouveaux médicaments, il devient de plus en plus évident que les produits naturels doivent être utilisés dans le processus de découverte de médicaments en tant que source d'inspiration.Par conséquent, de nombreuses stratégies émergent aujourd'hui pour la construction de chimiothèques inspirées par la nature, selon les stratégies "top-down" et "bottom-up". Dans les approches "bottom-up", la complexité est créée à partir de réactifs simples. En revanche, les approches "top-down" consistent à apporter des modifications structurelles à un produit naturel déjà complexe.Le travail présenté décrit deux approches différentes pour enrichir la chimiothèque de notre unité de recherche avec des composés dérivés de PNs. Une stratégie hémisynthétique "top-down" a été planifiée pour obtenir des dérivés de la lactucine et de la 11β,13-dihydrolactucine, deux lactones sesquiterpéniques extraites des racines de chicorée. 36 dérivés esters ont été synthétisés en trois étapes (synthèse classique), ainsi que deux bibliothèques de dérivés aminés (en utilisant la synthèse parallèle). Tous les composés ont ensuite été testés contre Mycobacterium tuberculosis et certaines molécules ont montré des activités prometteuses (CMI < 1,2 µM).D'autre part, une stratégie "bottom-up" a permis la synthèse de deux analogues de l'antibiotique naturel hygromycine A. Pour cette approche nous sommes partis de réactifs simples disponibles dans le commerce et avons appliqué une stratégie de déaromatisation dans le processus de synthèse.L'ensemble de ces travaux nous a permis d'explorer un espace chimique plus large, d'accroître la diversité structurelle de notre chimiothèque et de découvrir de nouveaux "hits". Nous pourrons également ainsi identifier de nouvelles cibles antibactériennes
Natural products (NPs) have declined in popularity since the introduction of synthetic small molecules several years ago. Many are the reasons behind this choice, such as difficulties in access and supply, complexities of NP chemistry and the advent of combinatorial chemistry. However, NPs offer many interesting properties compared to conventional synthetic molecules, which confer both advantages and challenges for the drug discovery process. Usually, NPs are characterized by a higher number of sp3 carbons and stereogenic centres, large scaffold diversity and structural complexity. With half of the drugs approved by the FDA since 1994 being NPs or hemisynthetic derivatives and the recent stagnation in new drug research and development, it is becoming more and more evident that NPs should be reintroduced in the drug discovery process as a source of inspiration.Therefore, many strategies are now emerging for the construction of nature-inspired chemical libraries, such as “top-down” and “bottom-up” strategies. In “bottom-up” approaches, complexity is created starting from simple building blocks. On the other hand, “top-down” approaches are assumed to make structural modifications to an already complex NP.Our presented work describes two different approaches to enrich the chemical library of our research unit with NP-derived compounds. A “top-down” semisynthetic strategy was planned to obtain derivatives of lactucin and 11β,13-dihydrolactucin, two sesquiterpene lactones extracted from chicory roots. Thirty-six ester derivatives were synthesized in three steps (classical synthesis), together with two amine derivative libraries (using parallel synthesis). All the compounds were then tested against Mycobacterium tuberculosis and some promising hits were found (MICGFP < 1.2 μM). On the other hand, a “bottom-up” strategy allowed the synthesis of two analogues of the known natural antibiotic hygromycin A. This approach started from simple commercially available building blocks and employed a dearomatization strategy in the synthetic process.Together, we explored a broader chemical space, increased the structural diversity of our chemical library and discovered new potential antibacterial hits. Moreover, this work paves the way for the discovery of new antibacterial targets