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The composition of the essential oil and of the hexane extract of the stem bark of Aniba canelilla was analyzed by means of GC/MS, MS and NMR spectroscopy. In addition to confirming the presence of some previously identified constituents such as 1-nitro-2-phenylethane, safrole and eugenol, this study allowed us to identify β-sitosterol, α-pinene, β-pinene, benzaldehyde, phenylacetaldehyde, methoxy eugenol, methyl eugenol, and (−)-selin-11-en-4α-ol. 1-Nitro-2-phenylethane was found to exhibit a high toxicity towards yeasts especially Candida albicans. The LD50 of a petroleum ether extract from this plant was determined to be greater than 800 mg/kg for BALB/c mice.

Within the last 25 years, matrix-assisted laser desorption ionization (MALDI) has become a powerful analytical tool in mass spectrometry (MS). While the method has been successfully applied to characterize large organic molecules such as proteins, sugars and polymers, its utilization for small molecules (≤ 600 Da) is significantly impaired by the coformation of matrix ions. Reducing or eliminating matrix-related signals has been subject of many studies. Some of which propose the enhancement of so-called matrix suppression effects, while others suggest the replacement of matrix molecules by materials such as microporous silicon. Alternatively, the immobilization of matrix molecules by utilizing them as self-assembled monolayers (SAMs) has been discussed. In continuation of this research, the current manuscript focuses on the elucidation of ion formation processes occurring on the surface of light absorbing SAMs. Ion yields obtained by free and immobilized matrix molecules as well as those generated by matrix-free gold film-assisted laser desorption ionization (GF-LDI) were compared. Experiments showed that the formation of strong analyte signals essentially required the presence of free matrix molecules, while the immobilization of the latter severely impaired ionization. The observed effect inversely correlated with the surface coverage of SAMs determined by cyclic voltammetry (CV). Based on these findings, the MS signal generated on light absorbing SAMs could be used supplementary to CV for determining the surface coverage of light absorbing SAMs.

International audience; Clusiaceae plants display high contents of xanthones and coumarins, the effects of which on endothelium, more particularly on angiogenesis, have not been assessed yet. We screened the capacity of six molecules from Clusiaceae - belonging to xanthones, coumarins and acid chromanes classes - to induce endothelium-dependent relaxation on mice aortic rings. Endothelial nitric oxide (NO) production was assessed in endothelial cell line using electron paramagnetic resonance technique. Then, the capacity of these molecules to induce capillary-like structures of endothelial cells was assessed. Cellular processes implicated in angiogenesis (adhesion, migration and proliferation) and Western blot analyses were then investigated. Among the tested molecules, isocalolongic acid (IA) and 2-deprenylrheediaxanthone (DRX) induced an endothelium-dependent relaxation of the aorta associated with an increase of NO production in endothelial cells. Using in vitro and ex vivo angiogenesis assays, it was shown that IA treatment promoted the formation of capillary-like network. In contrast, DRX prevented the ability of vascular endothelial growth factor (VEGF) to increase the formation of capillary-like network. IA increased endothelial cell proliferation while DRX decreased all cellular processes of angiogenesis. Western blot analysis showed that IA increased VEGF expression whereas DRX decreased ICAM-1 expression. Altogether, these data allowed identifying isolated molecules from Clusiaceae that exhibit a potential activity towards the modulation of endothelium-dependent relaxation involving NO release. Interestingly, they also highlighted paradoxical effects of the two compounds on cellular angiogenic processes, IA being pro-angiogenic and DRX anti-angiogenic.

International audience; Polyphenolic compounds have created an increasing interest for their potency about cardiovascular diseases for several years1-2. Nevertheless, most of this research had been focused on polyphenolic compound such as flavanols (e.g. catechine from tea), anthocyanin (e.g. delphinidin from blueberry) and stilbenoides (e.g. resveratrol from grape).The present study was designed to screen the potent effect of polyphenolic compounds isolated from plants belonging to Clusiaceae family on endothelium. A huge number of polyphenols such as xanthones and coumarines have been identified from those species and some of them exhibiting various biological activities such as anti-inflammatory and antioxidant properties3-4. Their effect on endothelium, more particularly on angiogenesis, is not yet well-known. Firstly, we assessed the capacity of six molecules to induce endothelium-dependent relaxation in mice aortic rings involving nitric oxide production. Isocalolongic acid (A1) and 2-deprenylrheediaxanthone (A2) are able to increase NO production on endothelial cells and to induce endothelium-dependant relaxation. Then, we investigated the effects of these compounds on in vitro and ex vivo angiogenesis. We showed that A1 treatment promoted the formation of capillary-like network contrary to A2. Endothelial cell adhesion, migration and proliferation were decreased in presence of A2 whereas endothelial migration and proliferation were improved with A1 treatment. We could explain these results with the capacity of A1 to increase VEGF expression and for A2, to decrease ICAM-1 expression. Thus, the strategy used for the screening allows the detection of active molecules from Clusiaceae family that might be of therapeutic benefit in cardiovascular diseases5.

Eleven benzyltetrahydroisoquinoline alkaloids, with an original substitution pattern, were isolated from the stem bark of Aniba canelilla H.B.K. (Lauraceae). Structural studies of these compounds including 1H, 13C, nOe difference, COSY H–H and C–H, and COLOC nuclear magnetic resonance spectroscopy led to the identification of four benzylisoquinolines, monosubstituted on ring C with an hydroxyl at C-11, (−)-norcanelilline 2, (+)-canelilline 3, anicanine 4, and canelillinoxine 5; two tetrahydroprotoberberines monosubstituted on ring D at C-9, (−)-anibacanine 6 and (+)-manibacanine 8; two tetrahydroprotoberberines monosubstituted on ring D at C-11, (−)-pseudoanibacanine 7 and (+)-pseudomanibacanine 9; and three protoberberines with the same substitution pattern on rings A and D with a methyl substituent at the 8α or 8β position, (−)-α-8-methylpseudoanibacanine 10, (−)-β-8-methylpseudoanibacanine 11, and (−)-α-8-methylanibacanine 12. An examination of all isolated alkaloids suggests the existence of two enzymatic systems in A. canelilla. In the first enzymatic system, reticuline- and coclaurine-type alkaloids are involved in the bioconversion of classical proaporphine and aporphine alkaloids. In the second system, canelilline-type alkaloids are intermediate in biosynthesis of anibacanine and pseudoanibacanine protoberberine alkaloids.

A new stilbene dimer, heimiol A was isolated from the heartwood of Neobalanocarpus heimii , in addition to the four known oligostilbenoids, balanocarpol, copalliferol A, hopeaphenol and vaticaphenol A. The structures and relative configuration were established by means of 2D NMR spectroscopy including COSY, HMQC, HMBC and NOESY.

(R)-(+)-Noranicanine (1a), a new type of benzylisoquinoline precursor was isolated from Aniba canelilla (Lauraceae) and its structure was determined by means of spectroscopic data as well as by synthesis

Photooxygenation (1O2) of ortho-prenylphenols followed by a reduction (PPh3) at low temperature (−30°C) yields a mixture of ortho-(2-hydroxy-3-methylbut-3-enyl)phenols and ortho-(3-hydroxy-3-methylbut-1-enyl)phenols. However, by running the two-step sequence at a higher temperature (15°C), the secondary allylic alcohol could be selectively recovered.

A new stilbene dimer, heimiol A was isolated from the heartwood of Neobalanocarpus heimii , in addition to the four known oligostilbenoids, balanocarpol, copalliferol A, hopeaphenol and vaticaphenol A. The structures and relative configuration were established by means of 2D NMR spectroscopy including COSY, HMQC, HMBC and NOESY.

International audience; The semisynthesis of xanthanolide derivatives is reported from xanthinin and 4-epi-isoxanthanol, two sesquiterpene lactones isolated from the crude chloroformic extract of the leaves of Xanthium macrocarpum DC. (Asteraceae) by liquid/liquid chromatography. In vitro evaluation of their protein farnesyltransferase (PFTase) inhibitory activity has been investigated. In contrast to other biological activities of xanthanolides, PFTase inhibition is not associated with the presence of the potentially toxic alpha-methylene-gamma-lactone function.

International audience; Scedosporium apiospermum is an emerging pathogen colonizing the airways of patients with cystic fibrosis (CF). While usually responsible for chronic colonization without clinical signs, this fungus may cause severe and often lethal infections in lung transplant recipients. Early diagnosis of its airway colonization and appropriate treatment are required to eradicate the fungus when a lung transplantation is planned. Here we propose an alternative to mycological examination of sputum samples based on extraction of siderophores by chromatography on Amberlite XAD-4, followed by high performance liquid chromatography analysis of the siderophore extract. Improvement of the extraction procedure was performed in a fractional factorial design which revealed the importance of prior ammonium sulfate precipitation of the proteins, alkalinization of the obtained solution and stirring during extraction. In order to verify the specificity of Nα-methyl coprogen B for S. apiospermum, the method was applied on culture supernatants of different filamentous fungi colonizing the airways of CF patients, including some aspergilli and Exophiala dermatitidis. Nα-methyl coprogen B was detected exclusively for species of the S. apiospermum complex. Likewise, sputum samples from colonized and non-colonized CF patients were analyzed, and the siderophore was detected exclusively in three out of the five specimens which were found by culture to contain S. apiospermum. Together these results confirmed Nα-methyl coprogen B as a marker of the airway colonization by species of the S. apiospermum complex.

International audience; Flavonoids are a group of polyphenol compounds with known antioxidant activities. Among them, dihydrochalcones are mainly found in apple leaves (Malus domestica). Glycosylated dihydrochalcones were previously found in large amounts in leaves of two genotypes of Malus with contrasting resistance to fire blight, a bacterial disease caused by Erwinia amylovora. In the present study we demonstrate that soluble polyphenol patterns comprised phloridzin alone or in combination with two additional dihydrochalcones, identified as sieboldin and trilobatin. Presence of sieboldin in young leaves correlated well with a high 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Moreover, these leaves displayed enhanced tolerance to paraquat, a photooxidative-stress generating herbicide. Interestingly, phloridzin had a high activity in the oxygen radical absorbance capacity (ORAC) assay, but its presence alone in leaves did not correlate with tolerance to paraquat. In order to further characterise the activity of these compounds, we tested their ability to prevent oxidative-dependent formation of advanced glycation end-products (AGEs) and phenylephrine-induced contraction of isolated rat mesenteric arteries. The antioxidant capacity of sieboldin was clearly demonstrated by showing that this compound (i) prevented vasoconstriction and (ii) inhibited AGEs formation. Both assays provided interesting information concerning a potential use of sieboldin as a therapeutic. Hence, our results strongly argue for a bioactivity of dihydrochalcones as functional antioxidants in the resistance of Malus leaves to oxidative stress. In addition, we demonstrate for the first time that sieboldin is a powerful multipotent antioxidant, effective in preventing physiopathological processes. Further work should aim at demonstrating the potential use of this compound as a therapeutic in treating free radical-involving diseases.

International audience; Alkaloids from Thalictrum flavum L. (Ranuculaceae) growing in the Loire valley (France) were isolated and evaluated for their antiplasmodial and leishmanicidal activities. Berberine was identified as a major component but its analogue, pseudoberberine, was isolated for the first time from this plant. As far as bisbenzylisoquinolines are concerned, thalfoetidine was also isolated and, besides, its nor- derivative, northalfoetidine, was identified as a new compound. Previously isolated alkaloids from Thalictrum species such as northalidasine, northalrugosidine, thaligosidine, thalicberine, thaliglucinone, preocoteine, O-methylcassythine and armepavine were newly described in the roots of T. flavum. Tertiary isoquinolines, and particularly bisbenzylisoquinolines, were found to be leishmanicidal against L. major. Thalfoetidine appeared as the most potent but its new nor- derivative northalfoetidine, as well as northalidasine, were of particular interest due to the fact that their potential leishmanicidal activity was not associated to a strong cytotoxicity.

International audience; The trans-fusarinine backbone is a common feature encountered in many fungal siderophores. This monomer is notably the structural base of Nα-methyl coprogen B and dimerumic acid. Both siderophores are known to be secreted by Scedosporium apiospermum, an emerging pathogenic fungus studied for its high involvement in invasive infections of immunocompromised patients. The strategy developed here for the synthesis of the trans-fusarinine scaffold relies on the preparation of both N-hydroxyornithine and 3-anhydroxymevalonic acid subunits starting from l-ornithine and 3-butyn-1-ol, respectively. The coupling of these two building blocks led to the expected protected backbone.

International audience; The genus Derris Loureiro belongs to the tribe Milletiae of the Leguminosae. It includes about fifteen species widely found in the tropical areas of Africa and Asia [1]. These plants have been traditionally used over centuries as fish poisoning, insecticide and pesticide, particularly due to their large production of rotenone [2]. Biological activities of Derris species are various: cytotoxic, antibacterial, antifungal, and antioxidant [3,4,5]. Though major secondary metabolites found in the genus are known to be flavonoids, including prenylated flavanones, and isoflavonoids such as rotenoids, very few phytochemical informations were available on D. ferruginea [6].Different crude extracts were obtained from the stem (2kg, Soxhlet apparatus). They were fractionated using successively MPLC, LC, FCPC® (Fast Centrifugal Partition Chromatography, Kromaton Angers), Sephadex LH-20® gel and finally purified on preparative HPLC. Chemical structures of the isolated compounds were elucidated using 1H and 13C NMR spectrum as well as Mass Spectrometry. Most of these compounds were identified as prenylated flavonoids (flavanones and isoflavonoids). Biological effects of these compounds will be reported here, particularly antimicrobial, antiparasitic activities and inhibition of the formation of AGEs (Advanced Glycation End Products involved in age- and diabetes-related chronic diseases).

International audience; Scedosporium apiospermum is an emerging pathogen colonizing the airways of patients with cystic fibrosis and causing severe infections in immunocompromised hosts. In order to improve our knowledge on the pathogenic mechanisms of this fungus, we investigated the production of siderophores. Cultivation on CAS medium and specific assays for different classes of siderophores suggested the secretion of hydroxamates. A maximal production was obtained by cultivation of the fungus at alkaline pH in an iron-restricted liquid culture medium. Siderophores were then extracted from the culture filtrate by liquid/liquid extraction, and separated by reverse phase high performance liquid chromatography. Two siderophores, dimerumic acid and N α-methyl coprogen B, were identified by electrospray ionization-mass spectrometry and MS–MS fragmentation. Finally, comparison of various strains suggested a higher production of N α-methyl coprogen B by clinical isolates of respiratory origin. Studies are initiated in order to determine the potential usefulness of these siderophores as diagnostic markers of scedosporiosis.

Présenté lors de la Conference: 55th International Congress and Annual Meeting of the Society-for-Medicinal-Plant-Research-and-Natural-Product-Research Location: Geneva, SWITZERLAND Date: AUG 16-20, 2009 Sponsor(s):Soc Medicinal Plant & Nat Prod Res; Genus Hydrangea: diversity of pigments and phenolic compounds

International audience; Anacardium occidentale L. (A. occidentale), belonging to Anacardiaceae family, has been documented as traditional plant for the treatment of diabetes and hypertension [1]. Four extracts of A. occidentale were used for this study, namely AOL1 (from cyclohexane), AOL2 (from CH2Cl2), AOL3 (from EtOAc) and AOL4 (from MeOH). The most potent antiradical reactivity was observed in AOL4 with 2023 TE/g of extract compared to chlorogenic acid (2976 TE/g of compound) as positive standard. In the other hand, our data showed a significant inhibitory effect of EtOAc and MeOH extracts on BSA glycoxidation measured in terms of advanced glycation end products (AGEs). In isolated mesenteric artery rings precontracted with phenylephrine [2], AOL1, AOL2, AOL3, and AOL4 induced a concentration-dependant relaxation respectively with IC50 values of 120µg/ml, 100µg/ml, 70µg/ml and 70µg/ml. Exposure of Eahy cells to high glucose for 7 days significantly (p

International audience; Plants are one of the major sources for the biologically active organic compounds and play a key role in medicinal chemistry for the treatment of various diseases [1]. DIAMS method is able to determine the secondary metabolites of complex vegetal extracts. The high throughput analyses of vegetal extracts are relatively difficult to perform in MALDI mass spectrometry, since the preparation of the sample involves the co-crystallization of the matrix with the analyte. Moreover irradiation of the matrix ion produces many low-m/z vs high-intensity ions preventing the detection of low molecular weight molecules such as secondary metabolites. We have developed a matrix-free alternative to MALDI analyses by the means of an original desorption/ionization on self-assembled monolayers surfaces (DIAMS) technique [2]. Monolayers were formed by using novel thiophene and coumarin-triazole analogues that absorbs the laser beam at 337nm. We herein disclose our findings with respect to the DIAMS method which is well suitable for the detection and quantification of the low molecular weight compounds that are present in plant extracts. Some of the isoquinoline alkaloids from the root extracts of Thalictrum flavum have been detected by the DIAMS method. Indeed, this technique would be promising suitable for the qualitative and quantitative analysis of polar and non-polar organic components that are widely distributed in the plants, without any preliminary chromatographic resolution [3].

International audience; Calophyllum species (Clusiaceae) are known as a rich source of various secondary metabolites and prenylated phenolic derivatives [1] are very common among them. As part of our continuing phytochemical investigation on Calophyllum species from Malaysia [2] we report here our results on the fractionation of different crude extracts obtained from two endemic species -Calophyllum flavo-ramulum and C. wallichianum- which exhibited significant anti-oxidant activities. This study mainly resulted in the identification of phenolic derivatives among which prenylated xanthones and biflavonoids (amentoflavone) appeared as the active principles. The structure of flavoramulone, a new xanthone exhibiting a quite unusual α-dimethyl β-hydroxy tetrahydropyrane was determined through extensive NMR studies.

The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to these structures. In vitro antimalarial activity of the 1,2-dioxolane derivatives has been investigated.

International audience; The phytochemical study of the bark of Malaysian Phoebe scortechinii (Lauraceae) has resulted in the isolation and identification of two new proaporphine alkaloids; (+)-scortechiniine A (1) and (+)-scortechiniine B (2) together with two known proaporphines; (-)-hexahydromecambrine A (3), (-)-norhexahydromecambrine A (4), and one aporphine; norboldine (5). Structural elucidations of these alkaloids were performed using spectroscopic methods especially 1D and 2D (1)H and (13)C NMR.

International audience; Seven xanthones, the new vieillardiixanthones B and C (1) and (7), pancixanthones A (2), B (3), 1,6-dihydroxyxanthone (6), pyranojacareubin and 5,6-O-dimethyl-2-deprenylrheediaxanthone together with two benzophenones, clusiachromene (4) and 3-geranyl-2,4,6-trihydroxybenzophenone (5) were isolated from the stem bark of the neocaledonian Garcinia vieillardii. 2, 5 and 6 showed a significant antileishmanial activity against the promastigote forms of Leishmania mexicana and L. infantum and against the amastigote forms of L. infantum.

International audience; Originating from America and introduced a few centuries ago in Europe, Xanthium macrocarpum DC. (Asteraceae) also called „Lampourde à gros fruits“ is a species commonly growing on the edges of the Loire. Xanthanolides (sesquiterpene lactones) found in this plant exhibit interesting biological activities [1]. These activities are usually explained by their alkylating properties due to the presence of the α-methylene-γ-lactone function which is also related to the toxicity of several plants. As recent reports pointed out the potential of dimeric or monomeric sesquiterpene lactones as farnesyltransferase (PFTase) inhibitors, we decided to explore this activity knowing that PFTase is an interesting target to find new effective therapeutic agents for the treatment of cancer. So, the objective was to obtained atoxic hemisynthetic derivates from the natural xanthanolides: xanthatin and xanthinin. These compounds were first isolated in one step from the crude chloroformic extract of the leaves of X. macrocarpum using differents methods of chromatography: silica gel and a 5L pilot scale FCPC® (Fast Centrifungal Partition Chromatograph, Kromaton, Angers, France). We have shown that FCPC® is more efficient for purification: solvent consumption is lowered (divided by 2), with highest purity (5 fold increase on average), high loading capacity (2g of extract/L of organic solvent), and manipulation time reduction (few hours versus few days) [2]. Sixteen derivates were investigated as potent inhibitors of protein farnesyl transferase. These results showed that the α-methylene-γ-lactone function is not required to insure a PFTase inhibitory activity whereas the α-methyl-γ-lactone function is responsible for a non competitive-inhibition.

Background: Formation and accumulation of advanced glycation end-products (AGE) is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities. Materials and Methods: ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively. Results: the root extract of C. fistula (IC50= 0.1 mg/mL) and the leaf extract of P. auritum (IC50= 0.35 mg/mL) presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. Conclusions: the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism. SUMMARY Ethanolic extracts from nine plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine were tested for their anti-AGE and free radical scavenging activities.Significant activity against vesperlysine and pentosidine-like AGE was detected in the root extract of Cassia fistula and the leaf extract of Piper auritum.Traditional preparations and the ethanolic extracts of Ehretia tinifolia, Manilkara zapota, Ocimum campechianum and Piper auritum showed significant activity in the DPPH reduction assay.Results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation. Abbreviations Used: AGE: Advanced glycation end-product; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; DM: Diabetes mellitus; ROS: Reactive oxygen species; BSA: Bovine serum albumin; EtOH: Ethanol; EtOAc: Ethyl acetate; ANOVA: Analysis of variance; BA: Brosimum alicastrum; BS: Bunchosia swartziana; CF: Cassia fistula; CN: Cocos nucifera; ET: Ehretia tinifolia; MZ: Manilkara zapota; OC: Ocimum campechianum; PA: Piper auritum; RM: Rhizophora mangle; L: Leaves; S: Stems; R: Roots; T: traditional preparation; I: Inflorescences; W: Water

International audience; In vivo detection and quantitation of metabolites is often limited by their low concentration. As far as magnetic resonance spectroscopy (MRS) is concerned, detection and quantitation can be significantly improved by reduction of the observed spectral width (SW). The reduction is limited to the spreading of resonances in the bandwidth unless high performance digital filters are used. Indeed, these filters avoid the folding of unwanted resonances such as water peak into the main frequency spectrum and therefore allow reduction of the spectral width to its optimal value. These filters are now available on most MRS systems but their use is not common even if, as we show in the particular case of proton MRS, a significant increase in signal-to-noise ratio (two-fold factor for SW reduction from 5000 Hz to 1351 Hz) can be achieved. This signal-to-noise improvement allows better quantitation accuracy.

New 2-(2,4-dihalogenophenyl)-1-(1H-imidazol-1-yl)-3-(isoxazol-5-yl)propan-2-ols and 2-(2,4-dihalogenophenyl)-1-(1H-imidazol-1-yl)-3-(4,5-dihydroisoxazol-5-yl)propan-2-ols were synthesized by 1,3-dipolar cycloaddition between homopropargylic or homoallylic alcohols and in-situ generated nitrile oxide. Their antifungal activity was evaluated against Candida albicans, C. glabrata, Aspergillus fumigatus and an azole-resistant petite mutant of C. glabrata. Preliminary SAR results are discussed.

Fagaronine derivatives syntheses were optimized and their effect on PC3 androgen-independent prostate cell line was evaluated. An assessment of the lipophilicity of the benzo[c]phenanthridine derivatives was achieved at pH 7.4 and et 6.7 by determining log D.

From the dichloromethane extract of the roots of Peucedanum paniculatum L., two new coumarins, a species endemic to Corsica, have been isolated. Their structures were elucidated, on the basis of spectroscopic studies, particularly 1D and 2D NMR spectroscopy, as 6-(7′-β-cyclolavandulyl)-7-hydroxycoumarin 1 and a spirodihydrofurano-coumarin 2 (Kallisteine A and B). Copyright © 2007 John Wiley & Sons, Ltd.

An in vitro MR-assay for superparamagnetic iron oxide (SPIO) particle cell labelling assessment via three-dimensional quantitative T(2) (*) MR microscopy was proposed. On high-resolution images, and due to the high susceptibility difference between the particles and the surrounding medium, SPIO internalized in cells induces signal loss which may be counted and measured on T(2) (*) maps. The increase in both labelled cell percentage and the average perturbation volume with an added amount of iron in the incubation medium proved that intracellular iron uptake is dependent upon the initial concentration of incubation iron. It also proved that the observed increases in total cellular iron uptake measured by inductively coupled plasma optical emission spectroscopy are due to both an increase in the iron mass per cell and also an increase in labelled cell concentration. MR results were compared with Prussian blue staining histology. The sensitivity of the MR methodology was then used to distinguish labelling differences for two different types of particle coating.The MRI-assay we proposed is a compulsory tool to optimize labelling efficiency in order to improve in vivo cell detection. Key parameters for detection, such as the percentage of cell labelling, the effect on the image for a given amount of internalized iron and labelling distribution among a cell population, are easily obtained. The comparison of different contrast agents for labelling one cell type, the assessment of one type of contrast agent for labelling different cell types and/or the evaluation of labelling strategies, are possible without having recourse to classical methods, and provide improved accuracy, since the principle is based on intracellular relaxivity. Copyright (c) 2006 John Wiley & Sons, Ltd.

Plants of the Asteraceae family are known as a source of sesquiterpene lactones with interesting biological activities. The purification of several xanthanolides (xanthathin, 4-epi-xanthanol and 4-epi-isoxanthanol) was realized in one step, directly from the crude chloroformic extract of the leaves of X. macrocarpum by silica gel chromatography and for the first time by liquid/liquid chromatography (counter-current chromatography/centrifugal partition chromatography), using a FCPC 5L (Fast centrifugal partition chromatograph, Kromaton Technologies, Angers, France). Recovery, purity of xanthathin and solvent consumption were improved with the liquid/liquid chromatography compared to solid/liquid chromatography.

Two imaging methods, MSSAVE (Multiple echo SubSlice AVEraging imaging), based on sub-slice averaging and MGESEPI (Multiple echo Gradient-Echo Slice-Excitation Profile Imaging), based on over-sampling in the slice direction, are proposed for single-scan quantitative T2* evaluation with susceptibility artifact compensation. Their potentials in terms of sensitivity, minimum performance time, susceptibility artifact reduction and T2* quantitation quality, were compared with existing single-scan methods such as classical FLASH two- or three-dimensional or z-shimmed methods both in vitro and in vivo in normal rat brain. MGESEPI offered good quality T2* maps nearly free of artifacts but required a long acquisition time. MSSAVE was faster, but at the expense of reduced artifact compensation and the achievable T2* quantitation quality. Copyright © 2006 John Wiley & Sons, Ltd.

Three new 1-thioglycosides namely methylthiomethyl 1-thio-β- d -glucopyranoside (Afrostyraxthioside A), methylsulfonylmethyl 1-thio-β- d -glucopyranoside (Afrostyraxthioside B) and methylsulfonylmethylthiomethyl 1-thio-β- d -glucopyranoside (Afrostyraxthioside C) were isolated from the seeds of Afrostyrax lepidophyllus Mildbr. Their structures were mainly elucidated by using one- and two-dimensional NMR and mass spectroscopies and also by an efficient one-step synthesis. Moreover, Afrostyraxthiosides A, B and C constitute a new subclass of 1-thioglycosides isolated from natural sources.

A set of 32 natural and synthetic coumarins were tested in order to evaluate their activity on human leukemic cells (K562/R7) overexpressing P-glycoprotein (P-gp). Their ability to reduce the P-gp-mediated drug efflux of daunorubicin out of cells was evaluated at 10 microM. Four natural compounds, previously isolated from Calophyllum dispar (Clusiaceae) and substituted by a common alpha-(hydroxyisopropyl)dihydrofuran moiety, exhibited a significant inhibitory effect on P-gp when compared to the positive control cyclosporin A. A 3D-quantitative structure-activity relationship (3D-QSAR) analysis of the coumarins was performed using the biological results obtained by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of P-gp. Results showed a favorable electrostatic and steric volume, like the alpha-(hydroxyisopropyl)dihydrofuran moiety, beside C(5)-C(6) or C(7)-C(8) positions. In addition, the analysis revealed an important hydrophobic, neutral charge group, like phenyl, in position C(4) on the coumarinic ring.

There are thirteen endemic species belonging to the genus Garcinia in New Caledonia. Among them, G. virgata is an evergreen tree mainly growing in the rain forests of this island. Fractionation of the cyclohexane extract of the stem bark of this plant produced the known benzophenones guttiferone E and xanthochymol, together with two new guttiferone analogues, namely guttiferones I and J. The structures of these benzophenones were mainly elucidated using 1D and 2D NMR spectroscopy. Compounds and were weakly cytotoxic on the KB cell line with IC50 values of 4.70 and 5.0 microg/mL respectively.

The synthesis of new xanthanolide derivatives is reported starting from xanthatin, a sesquiterpenic lactone isolated from Xanthium macrocarpum (Asteraceae). In vitro evaluation of their antifungal activity has been investigated.

The antimalarial activity of 22 xanthones against chloroquino-resistant strains of Plasmodium falciparum was evaluated. Natural caloxanthone C (1), demethylcalabaxanthone (2), calothwaitesixanthone (3), calozeyloxanthone (4), dombakinaxanthone (5), macluraxanthone (6), and 6-deoxy-gamma-mangostin (7) were isolated from Calophyllum caledonicum. 1,6-dihydroxyxanthone (8), pancixanthone A (9), isocudraniaxanthone B (10), isocudraniaxanthone A (11), 2-deprenylrheediaxanthone B (12) and 1,4,5-trihydroxyxanthone (13) were isolated from Garcinia vieillardii. Moreover, synthetic compounds (14-22) are analogues or intermediates of xanthones purified from Calophyllum caledonicum (Oger J.M., Morel C., Helesbeux J.J., Litaudon M., Seraphin D., Dartiguelongue C., Larcher G., Richomme P., Duval O. 2003. First 2-Hydroxy-3-Methylbut-3-Enyl substituted xanthones isolated from Plants: structure elucidation, synthesis and antifungal activity. Natural Product Research 17(3), 195-199; Helesbeux J.J., Duval O., Dartiguelongue C., Seraphin D., Oger J.M., Richomme P., 2004. Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors. Tetrahedron 60(10), 2293-2300). The relationship between antimalarial activity and molecular structure of xanthones has also been explored. The most potent xanthones (2), (3) and (7) (IC50 = c.a. 1.0 microg/mL) are 1,3,7 trioxygenated and prenylated on the positions 2 and 8.

Two isomeric irregular sesquiterpene aldehydes, namely 3,9-dimethyl-6-isopropyl-2(E),7(E),9-decatrienal and 3,9-dimethyl-6-isopropyl-2(Z),7(E),9-decatrienal, were isolated from the essential oil of Santolina corsica and their structures were elucidated by 1D and 2D NMR spectroscopy.

Eudesm-5-en-11-ol was isolated from the oil of Helichrysum italicum and its structure was elucidated by 1D and 2D NMR spectroscopy.

Chromatographic, chemical, and spectroscopic techniques were used to characterize the physicochemical properties of napin purified by preparative chromatography. The molar extinction coefficient was determined (epsilon = 0.56), and static and dynamic light scattering measurements enabled the average molecular weight (M(w) = 13919), the second virial coefficient (A(2) = 23.95 x 10(-)(5) mol cm(3) g(-)(2)), and the hydrodynamic radius (R(H) = 1.98 nm) to be determined. No conformational changes were observed by fluorescence and circular dichroism measurements in different buffers at pH 3, 4.6, 7, and 12, confirming the high pH stability of this protein. From MALDI-TOF analysis and after enzymatic digestion, it was found that this purified sample, extracted from the rapeseed variety Express, contained mainly isoform 2SS3_BRANA.