Brigitte Deguin

Cytotoxic activity and inhibitory effect on nitric oxide production of triterpene saponins from the roots of Physospermum verticillatum (Waldst & Kit) (Apiaceae)

Three triterpene saponins isolated from the roots of Physospermum verticillatum and identified as saikosaponin a (1), buddlejasaponin IV (2), and songarosaponin D (3) were investigated in vitro for their cytotoxic activity against a panel of seven different cancer cell lines including ACHN, C32, Caco-2, COR-L23, A375, A549, and Huh-7D12 cell lines. The hydrolysis of sugar unit was performed on saikosaponin a (1) to obtain saikosapogenin a (4). All isolated saponins exhibited strong cytotoxic activity against COR-L23 cell line with IC(50) values ranged from 0.4 to 0.6 microM. A similar activity was recorded for saikogenin a (4). None of the tested compounds affected the proliferation of skin fibroblasts 142BR suggesting a selective action against cancer cells. Moreover, buddlejasaponin IV (2) and songarosaponin D (3) exerted significant inhibition of NO production in LPS induced RAW 264.7 macrophages with IC(50) of 4.2 and 10.4 microM, respectively.

In vitro biological evaluation of novel 7-O-dialkylaminoalkyl cytotoxic pectolinarigenin derivatives against a panel of human cancer cell lines

The effect of novel pectolinarigenin derivatives bearing a dialkylaminoalkyl substituent at O-7 on cell proliferation was evaluated in vitro in a panel of seven human cancer cell lines including renal adenocarcinoma ACHN, amelanotic melanoma C32, colorectal adenocarcinoma Caco-2, lung large cell carcinoma COR-L23, malignant melanoma A375, lung carcinoma A549 and hepatocellular carcinoma Huh-7D12 cell lines. Pectolinarigenin (2), obtained by hydrolysis of rutinose unit of the pectolinarin (1) isolated from Linaria reflexa, exhibited cytotoxic activity against Caco-2, A549 and A375 cell lines with IC(50) values of 5.3-8.2 microM. The most active pectolinarigenin derivative was 3 characterized by a dimethylamino-propoxy group in O-7 with IC(50) values of 7.2 and 7.4 microM against COR-L23 and A549 cell lines, respectively. A structure-activity relationship analysis of synthesized compounds was performed. None of the tested compounds affected the proliferation of skin fibroblasts 142BR suggesting a selective activity against tumor cells.

Chemical Composition and Antimicrobial Activity of the Essential Oils of Anthospermum emirnense and Anthospermum perrieri (Rubiaceae)

The essential oils of Anthospermum emirnense Baker and Anthospermum perrieri Homolle ex Puff, obtained by hydrodistillation in 0.03 and 0.02% yield, respectively, were analyzed by GC/MS. In both cases, the major constituents consisted of sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The two species showed an important qualitative similarity, with 40 compounds common to A. emirnense and A. perrieri, including β‐elemene, trans‐β‐caryophyllene, caryophyllene oxide, and τ‐cadinol, which were major components in both cases. When tested for antimicrobial activity, both essential oils showed similar profiles and exhibited interesting minimal‐inhibitory‐concentration (MIC) values towards Bacillus subtilis, Chryseobacterium indologenes, Flavimonas oryzihabitans, and Yersinia enterocolitica.

Antivascular and anti-parasite activities of natural and hemisynthetic flavonoids from New Caledonian Gardenia species (Rubiaceae)

A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanosoma brucei gambiense, in addition to tubulin polymerization inhibition at low micromolar concentration. We also provide a full set of NMR data as some of the flavones were incompletely described.

A novel series of cytotoxic iridoid glucosides derived from aucubin: Design, synthesis and structure–activity relationships

Five new unsaturated iridolactones 3-7 related to natural cytotoxic oxylipins, Tei 9826, and iridolactone 2, were prepared by parallel synthesis from natural aucubin. It was found that perpivaloyl iridoid glucosides 2, 3, and 4 were markedly cytotoxic against both L1210 and KB-3-1 cell lines.

Mild and Chemoselective Lactone Ring-Opening with (TMS)ONa. Mechanistic Studies and Application to Sweroside Derivatives

Mild and chemoselective opening of lactones with sodium trimethylsilanolate in high yields and aprotic solvents is described. Kinetic studies demonstrate that the B(Ac)2 mechanistic pathway is followed. Nucleophilic attack of silanolate onto the carbonyl of the lactone moiety is the rate-determining step. NaOH present as an impurity accelerates the reaction. The method was further applied to the base-sensitive and stable lactones derived from highly functionalized iridoid derivatives.

Large scale purification of the SERCA inhibitor thapsigargin from Thapsia garganica L. roots using centrifugal partition chromatography.

Thapsigargin (Tg) is a selective and irreversible inhibitor of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)-dependent pump at subnanomolecular concentrations. As such, it has become a powerful tool in the study of Ca(2+) signaling pathway. Purification of Tg from Thapsia species requires repeated chromatographic steps with normal-phase alumina or silica and reverse phase chromatography. We thus developed an innovative procedure coupling high pressure automatized extraction with centrifugal partition chromatography allowing a fast and safe large-scale isolation of highly pure Tg, in two steps from Thapsia garganica L. roots. Comparison of influence of extraction procedures, storage conditions and harvesting areas on Tg content in different Algerian specimens of Thapsia garganica L. roots has been precised by mean of HPLC quantification procedure. Highest Tg content were found in the fresh material of the sample from Setif area.

Lewis acid catalyzed enlargement of cyclic β-alkoxyenals and one-pot synthesis of polyfunctional enoxysilanes derived from aucubin with trimethylsilyldiazomethane.

Aldehyde and ketone homologations, such as the Tiffeneau–Demjanov–Tchoubar rearrangement with diazoACHTUNGTRENNUNGmethane are well studied reactions and lead to various products depending on the nature of substrates and reaction conditions. Employment of trimethylsilyldiazomethane (TMSDM) instead of CH2N2 makes the reactions safer and allows us to capitalize on the rearrangement of the resulting b-silylcarbonyl compounds. These reactions require nonprotic anhydrous conditions to avoid protolysis of the targeted enoxysilanes. Efforts to find methodologies to convert aldehydes and ketones into homologated enoxysilanes of type 6 and 8 by using TMSDM or TMSC(Li)N2, in onestep protocols, have been presented (Scheme 1). In the case of aldehydes reacting with TMSDM, the product distribution 6 versus 8 depends on the relative rates of alkyl, aryl, and alkenyl group migration 2!3 versus hydride migration 2!5 and epoxide formation 2!4 (Scheme 1). However, the reactions between TMSDM and cyclic aldehydes have been poorly studied. When enones were reacted, 1,4-addition of TMSDM and subsequent trimethylsilylcyclopropanation were observed. In this work, we disclose an unusual reaction of TMSDM with b-alkoxyenals. When cyclic b-alkoxyenals are employed (Scheme 2), ring enlargement might compete with the classical aldehyde homologations (Scheme 1) and with suitable Lewis acids may become the major process. This procedure has been applied to carbaldehydes derived from aucubin and it opens a new avenue for the one-pot conversion of these scaffolds into complicated polyfunctional enoxysilanes and their exploitation in semi-synthesis. To our knowledge this methodology represents the first ring expansion from balkoxyenals by using TMSDM in one step.

Chemical and Biological Investigation of Olive Mill Waste Water - OMWW Secoiridoid Lactones.

Olive mill waste water is the major byproduct of the olive oil industry containing a range of compounds related to Olea europaea and olive oil constituents. Olive mill waste water comprises an important environmental problem in olive oil producing countries, but it is also a valuable material for the isolation of high added value compounds. In this study, an attempt to investigate the secoiridoid content of olive mill waste water is described with the aid of ultrahigh-performance liquid chromatography-electrospray ionization (±)-high-resolution mass spectrometry and centrifugal partition chromatography methods. In total, seven secoiridoid lactones were isolated, four of which are new natural products. This is the first time that a conjugate of hydroxytyrosol and a secoiridoid lactone has been isolated from olive mill waste water and structurally characterized. Furthermore, the range of isolated compounds allowed for the proposal of a hypothesis for the biotransformation of olive secoiridoids during the production of olive mill waste water. Finally, the ability of the representative compounds to reduce the intracellular reactive oxygen species was assessed with the dichlorofluorescein assay in conjunction with the known antioxidant agent hydroxytyrosol.

HPLC-ELSD Quantification and Centrifugal Partition Chromatography Isolation of 8-O-Acetylharpagide from Oxera coronata (Lamiaceae)

INTRODUCTIONnIridoid glycosides possess highly functionalised monoterpenoid aglycon with several contiguous stereocentres. For the most common, they are often present in quantities reaching several percentage of the fresh plant weight, and thus they may be regarded as starting material for the synthesis of a number of new chiral and bioactive molecules.nnnOBJECTIVEnTo quantify and to isolate 8-O-acetylharpagide (AH) from several extracts of Oxera coronata R.P.J. de Kok, a Lamiaceae species endemic to New Caledonia, using HPLC-ELSD (evaporative light scattering detector) and centrifugal partition chromatography (CPC).nnnMETHODOLOGYnOxera coronata produces high amounts of AH in leaves, twigs and fruits. Water and methanol extracts of these plant parts were prepared. The content of AH in each extract was quantified by HPLC-ELSD, using acetonitrile-water (+0.1% formic acid) gradient elution. The HPLC method was validated for precision, linearity, limit of detection (LOD), limit of quantification (LOQ) and accuracy. A ternary solvent system ethyl acetate/n-propanol/water (3:2:5, v/v/v) was selected and applied to recover the target compound using Spot CPC from the leaves aqueous extract.nnnRESULTSnHPLC-ELSD analysis followed by CPC purification led to the efficient isolation of AH from O. coronata leaves aqueous extract.nnnCONCLUSIONnHPLC-ELSD has proven to be a well-adapted detection and quantification method for iridoid glycosides, while CPC confirmed to be an efficient technique for the isolation of polar compounds. Copyright