Investigation phytochimique et biologique d'espèces du genre Ferula. Synthèse d'analogues structuraux et étude de la relation structure-activité

Souhaitant valoriser des plantes médicinales non étudiées et découvrir de nouvelles substances naturelles biologiquement et pharmacologiquement actives, nous avons étudié quelques extraits volatils et non volatils des plantes Ferula tunetana L. et F. lutea (Poire) Maire. (Apiaceae). L'étude de la composition chimique des huiles essentielles des fleurs de F. lutea et des feuilles, graines, tiges et racines de la plante F. tunetana nous a permis d'identifier la majorité des constituants par la CPG, la CPG/SM et la RMN 13C. Les investigations phytochimiques entreprises sur deux extraits des fleurs de F. lutea, par les techniques chromatographiques liquides et préparatives sur colonne à pression atmosphérique (CC), chromatographie à haute pression (flash chromatographie) et CCM préparatives, nous ont permis d'isoler six produits de l'extrait butanolique. Deux nouveaux composés non cités dans la littérature (E)-5-ethylidenefuran-2(5H)-one-5-O-ß-D-glucopyranoside (P1) et l'acide 4-hydroxy-3, méthyl butanoique (P5) et trois produits isolés pour la première fois de cette plante : verbenone-5-O-ß-D-glucopyranoside (P2), caféate de méthyle (P3) et l'acide chlorogénique (P4). Nous avons pu aussi isoler de l'extrait à l'acétate d'éthyle des fleurs de F. lutea sept produits isolé pour la première fois de cette plante, 3, 5-O-dicaféoylquinate de méthyle (P6), l'acide 3,5-O-dicaféoylquinique (P7), narcissin (P8), (-)-Z-deltoine (P9), (-)-marmésine (P10), Isoimperatorine (P11) et 2,3,6 triméthyl benzaldéhyde (P12). Les structures de ces composés ont été élucidées à l'aide des méthodes spectroscopiques : spectrométrie de masse (DCI-SM, ES-SM), spectroscopie de RMN 1D et 2D (1H, 13C, HSQC, HMBC, COSY et NOESY) et le Rayon X pour le composé (P5). Nous avons isolé une bonne quantité de deltoine (P10) ce qui nous a permis d'effectuer des hémisynthèses d'une série 1,3 dipolaire pour accéder à de nouveaux isoxazolines (2a,a'-2g,g') et aziridines (3a,a'-3e,e') D'autre part, connaissant les propriétés biologiques des phénoliques, par exemple les flavonoïdes, nous avons synthétisé de nouveaux dérivés de type flavonole Flav1-Flav26. Les activités biologiques des huiles essentielles, extraits organiques, produits purs et les produits synthétisés ont été évaluées à l'aide de tests in vitro : activités microbiologique (contre diverses souches bactériennes et fongiques), antioxydante (envers les radicaux DPPH, ABTS), inhibitrice de 5-lipoxygénase et cytotoxique (sur une lignée cancéreuses coliques humaines HCT 116 et deux lignées ovariennes IGROV-1 et OVCAR-3)Wishing to enhance not studied medicinal plants and discover new biologically and pharmacologically active natural products, we studied some volatile and non-volatile extracts of plants: Ferula tunetana and F. lutea (Apiaceae). The chemical composition of the flower oil from F. lutea and the leaves, seeds, stems and roots of F. tunetana, obtained by hydrodistillation, were analyzed by combination of GC/FID, GC/MS and 13C-NMR spectroscopy. The phytochemical investigations of flowers of F. lutea undertaken on these two extracts using preparative liquid chromatographic column at atmospheric pressure (CC), high pressure chromatography (flash chromatography) and preparative TLC allowed us to isolate two new compounds from n-butanol (E)-5-ethylidenefuran-2(5H)-one-5-O-ß-D-glucopyranoside (P1), 4-hydroxy-3-methyl-but-2-enoic acid (P5 ), and three known compounds Verbenone-5-O-ß-D-glucopyranoside (P2 ), methyl caffeate (P3 ) and chlorogenic acid (P4 ). We were also isolated seven compounds isolated from the first time from ethyl acetate of flowers of F. lutea: methyle 3, 5-O-dicaffeoylquinate (P6), 3,5-O-dicafeoylquinic acid (P7), Narcissin (P8), (-)-Z-Deltoin (P9), (-)-marmesin (P10), Isoimperatorin (P11), 2,3,6 trimethyl benzaldehyde (P12). The pure compounds have had their structure elucidated using sepctroscopics methods: mass spectrometry (DCI-SM and ESI-MS) and NMR spectroscopy, 1D and 2D experiments (1H, 13C, HSQC, HMBC, COSY and NOESY) and diffraction of X-ray for compound (P5) We isolated a good quantity of Deltoin (10) which allowed us to perform a series hémisynthesis of 1,3-dipolar to access new isoxazolines and aziridines derivatives. Within the framework of synthesizing similar natural substances, we prepared a series of novel flavonol derivatives. The biological activities of essential oils, organic extracts, pure compounds and synthesized products were evaluated by in vitro bioassays: microbiological (against various strains of bacteria and fungi), antioxidant (towards radical DPPH and ABTS), 5-lipoxygenase inhibitory and cytotoxic (on one human colon cancer cell lines HCT 116 and two ovary cells lines IGROV-1 and OVCAR-3) activitie

Comparative study of in-vitro antioxidant, anti-acetylcholinesterase, anti-xanthine oxidase, anti-5-lipoxygenase, anti-α-amylase and cytotoxic activity of Acacia species (Mimosaceae)

The present study aimed the investigation of the acetylcholinesterase, xanthine oxidase (XOD), 5-lipoxygenase, α-amylase, antioxidant and cytotoxic activities of various organic extracts from seeds and pods of two Tunisian species of Acacia, A. cyclops and A. mollissima (Mimosaceae). At concentrations of 50 µg/mL, EtOAc extract of seeds from A. mollissima was able to strongly inhibit xanthine oxidase (XOD) with 98.40%. Moreover, EtOAc and n-BuOH extracts from pods of A. mollissima showed the highest inhibitor activity against 5-lipoxygenase with percentages of 79.60 and 64.86% inhibition, respectively. However, most of the tested extracts were not good acetylcholinesterase inhibitors. n-BuOH extracts of pods displayed the highest antioxidant activity (IC50= 36.03 to 45.90 µg/mL) for the DPPH assay and confirmed with the ABTS test. The eight extracts of Acacia species were tested for their cytotoxic activity in vitro using MCF-7, HCT-116, IGROV-1 and OVCAR-3 cell lines. The most active extracts were those of A. cyclops against IGROV-1 ranging from 12.9 to 16.1 µg/mL

Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities

International audienceIn our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC50 = 10.4 µM) was obtained for harmine 1 and cytotoxic activities (IC50 = 0.2 µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC50 = 29.2 and 55.5 µM, respectively)

GC and GC-MS integrated analyses and in vitro antibacterial, anticholinesterase, anti-tyrosinase, and anti-5-lipoxygenase potential of Inula viscosa root fractionated essential oil

Abstract The aim of this study was to characterize the chemical composition of the roots essential oil from Inula viscosa (L.) through its fractionation during extraction, and to evaluate the antibacterial, anticholinesterase, anti-tyrosinase and anti-5-lipoxygenase activities of the isolated oil (REO) and its fractions (R1–R10). The REO and its fractions (R1–R10) were isolated by hydrodistillation of the fresh roots in a Clevenger type apparatus. Fifty-three constituents were identified by GC-FID and GC–MS analyses. The REO was characterized by a high proportion of oxygenated monoterpenes (50.5%), followed by oxygenated sesquiterpenes (37.5%) and sesquiterpene hydrocarbons (7.6%). The major constituents of the REO and all the fractions were (Z)-neryl isovalerate (17.5–29.8%), 1,10-di-epi-cubenol (19.1–27.2%) and 2,5-dimethoxy-p-cymene (5.9–17.7%). The antibacterial activity of REO and its fractions (R1–R10) was tested by using the micro dilution methods against two Gram-positive and four Gram-negative bacteria. The REO and its fractions (R1–R10) showed a strong inhibition of Enterococcus faecalis (MIC = 20.0 μg/mL) and Staphylococcus aureus (MIC = 20.0 μg/mL). Results showed that the fraction R8 exerted the highest anti-tyrosinase activity, with 88.4% of inhibition at 50 μg/mL, and R1 exhibited a significant 5-lipoxygenase inhibitory effect (IC50 = 21.15 ± 0.12 μg/mL)

Chemical Composition, Biological and Cytotoxic Activities of Plant Extracts and Compounds Isolated from Ferula lutea

The present work describes the phytochemical study on Ferula lutea flowers. Total phenolics and flavonoids of the n-butanol and ethyl acetate extracts were quantified (phenolics [40.68–52.29 mg gallic acid equivalent/g of dry weight], flavonoids [12.38–14.72 mg quercitin/g dry weight]). Two diastereoisomers were isolated and identified using spectroscopic techniques (1D, 2D NMR and GC-MS). The extracts and diastereoisomers were tested for antioxidant, antiacetylcholinesterase, antimicrobial, antidiabectic, cytotoxic (leukemia cell line) activities and allelopathic potentialities. The strongest antioxidant activity was obtained for the ethyl acetate extract (IC50 = 12.8 ± 1.29 µg/mL). The two extracts exhibited high antidiabetic activity (54.1 and 52.1% at 40 µg/mL)

Chemical composition and biological evaluation of the resin from Tetraclinis articulata (Vahl.) Masters: A promising source of bioactive secondary metabolites

The identification of the volatile components of the resin from Tetraclinis articulata (Vahl.) Masters and its non-polar fractions 1–5 obtained by chromatographic simplification was investigated by GC-FID and GC–MS and allowed the identification of 97.3% (resin), 95.1% (1), 97.6% (2), 99.6% (3), 88.1% (4) and 95.0% (5) of the total volatile components. The resin and its fractions were characterized by the presence of a high amount of diterpenes (87.4, 80.1, 91.0, 91.6, 65.7 and 69.1%, respectively). The major identified diterpenes were trans-ferruginol (resin: 31.6%, 1: 56.5% and 2: 48.0%), manool (3: 57.0% and 4: 42.0%) and trans-totarol (5: 36.2%). In addition, trans-communic acid was isolated together with its cis diastereoisomer from the fraction 6 of the resin and identified by spectroscopic means (1D and 2D NMR) and by comparison with literature data. The resin, its fractions 1–5, trans-communic acid and cis-trans mixture were screened for their antioxidant activity using DPPH, ABTS, reducing power, catalase and paraoxonase methods, as well as for their antibacterial, anticholinesterase, anti-tyrosinase and cytotoxic potentials. The fraction 2 displayed the highest antioxidant activity (IC50= 25 ± 1 μg/mL and 64.1 ± 0.5 μM/min/L) in DPPH and paraoxonase assays, respectively. Trans-communic acid was found to be antibacterial against Staphylococus aureus and Enterococcus faecalis (IZ = 23.9 ± 1.5 and 20.5 ± 0.5 mm, respectively). Furthermore, the resin showed the best anti-tyrosinase activity with 87.2% of inhibition at 50 μg/mL and cis-trans mixture exerted a significant cytotoxic effect against HeLa cell line (IC50= 09.5 ± 1.0 μg/mL)

Antioxidant, 5-Lipoxygenase Inhibitory and Cytotoxic Activities of Compounds Isolated from the Ferula lutea Flowers

A phytochemical investigation of the Ferula lutea (Poir.) Maire flowers has led to the isolation of a new compound, (E)-5-ethylidenefuran-2(5H)-one-5-O-β-D-glucopyranoside (1), designated ferunide, 4-hydroxy-3-methylbut-2-enoic acid (2), reported for the first time as a natural product, together with nine known compounds, verbenone-5-O-β-D-glucopyranoside (3), 5-O-caffeoylquinic acid (4), methyl caffeate (5), methyl 3,5-O-dicaffeoylquinate (6), 3,5-O-dicaffeoylquinic acid (7), isorhamnetin-3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside, narcissin (8), (−)-marmesin (9), isoimperatorin (10) and 2,3,6-trimethylbenzaldehyde (11). Compounds 3–10 were identified for the first time in Ferula genus. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments, mass spectroscopy and X-ray diffraction analysis (compound 2), as well as by comparison with literature data. The antioxidant, anti-inflammatory and cytotoxic activities of isolated compounds were evaluated. Results showed that compound 7 exhibited the highest antioxidant activity with IC50 values of 18 ± 0.5 µmol/L and 19.7 ± 0.7 µmol/L by DPPH radical and ABTS radical cation, respectively. The compound 6 exhibited the highest anti-inflammatory activity with an IC50 value of 5.3 ± 0.1 µmol/L against 5-lipoxygenase. In addition, compound 5 was found to be the most cytotoxic, with IC50 values of 22.5 ± 2.4 µmol/L, 17.8 ± 1.1 µmol/L and 25 ± 1.1 µmol/L against the HCT-116, IGROV-1 and OVCAR-3 cell lines, respectively

New flavonoid glycosides conjugates: synthesis, characterization, and evaluationof their cytotoxic activities

International audienceA series of novel halogenated 3-hydroxyflavones (3HFs) were prepared by reacting halogenated hydroxyacetophenones with the appropriate aromatic aldehyde. Glycosylation of 3HFs with acetobromoglucose and deprotection of the acetyl protective groups afforded the desired 3-$O$-flavonoids glycosides in satisfactory yields. All the prepared compounds were tested for their cytotoxic activity against HCT-116, MCF-7, and OVCAR-3 human cancer cell lines. The 3HFs exhibited higher cytotoxic activities compared with the glycosylated flavonoids. Overall, the structure-activity relationship study showed that the introduction of glycoside moiety at the C-3 OH position does not improve the bioactivity

Design and semisynthesis of new herbicide as 1,2,3-triazole derivatives of the natural maslinic acid

International audienc