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A new isoflavone, 5,7-dihydroxy-4'-methoxy-3'-(2,3-dihydroxy-3-methylbutyl)isoflavone (1) was isolated from the stem bark of Ficus nymphaefolia Mill. (Moraceae) together with eight known isoflavones: genistein, erycibenin A, cajanin, 5,7,2'-trihydroxy-4'-methoxyisoflavone, erythrinin C, alpinumisoflavone, derrone and 3'-(3-methylbut-2-enyl)biochanin A. Their structures were established by spectral analysis including 1D and 2D NMR experiments.

International audience; Bioguided fractionation of the roots of Citrus sinensis (Rutaceae) led to the isolation and identification of five coumarins, namely, clausarin, suberosin, poncitrin, xanthyletin and thamnosmonin, seven acridones, namely, acrimarine B, 2-methoxycitpressine I, citpressine I, buntanine, acrimarine E, honyumine and acrimarine C, and one terpenoid, namely, limonin. Among these compounds, clausarin, 2-methoxycitpressine I and acrimarine E inhibited P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells over-expressing P-glycoprotein.Bioguided fractionation of the roots of Citrus sinensis (Rutaceae) led to the isolation and identification of five coumarins, namely, clausarin, suberosin, poncitrin, xanthyletin and thamnosmonin, seven acridones, namely, acrimarine B, 2-methoxycitpressine I, citpressine I, buntanine, acrimarine E, honyumine and acrimarine C, and one terpenoid, namely, limonin. Among these compounds, clausarin, 2-methoxycitpressine I and acrimarine E inhibited P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells over-expressing P-glycoprotein.

The first regioselective syntheses of 6-(1,1-dimethylallyl)- and 8-(3,3-dimethylallyl) chrysins have been designed. Claisen rearrangement of protected 5- O -(3,3-dimethylallyl) chrysin in N , N -diethylaniline at 200–217°C gave selective access to the 8-(3,3-dimethylallyl) isomer. Similar rearrangement in N , N -diethylbutylamine at 140–160°C, or in cycloheptane/Eu(fod) 3 at 100°C, led to the formation of the 6-(1,1-dimethylallyl) isomer. Four different protecting groups for position 7 of chrysin have been compared, and found to follow the order of interest Bz>MOM>TBDPS>MEM.

Regioselective control of the Claisen rearrangement of 7-MEM-5-prenyl chrysin was achieved by microwave irradiation. The nature of the products was influenced by the irradiation power and the type of solvent. Irradiation at 750 W in N,N-diethylaniline specifically yielded the 8-(3,3-dimethylallyl) para-rearranged product while refluxing in N,N-diethylbutylamine gave selective access to the 6-(1,1-dimethylallyl) ortho-rearranged compound.

A benzophenone glycoside has been isolated from Davallia solida. Its structure was elucidated by chemical and spectral means as 4-O-beta-D-glucopyranosyl-2,6,4'-trihydroxybenzophenone. It bound with moderate affinity to the purified C-terminal cytosolic domain of P-glycoprotein, but the binding affinity was 6- to 10-fold increased for its aglycone derivative and other related benzophenones.A benzophenone glycoside has been isolated from Davallia solida. Its structure was elucidated by chemical and spectral means as 4-O-beta-D-glucopyranosyl-2,6,4'-trihydroxybenzophenone. It bound with moderate affinity to the purified C-terminal cytosolic domain of P-glycoprotein, but the binding affinity was 6- to 10-fold increased for its aglycone derivative and other related benzophenones.

Analytical capillary zone electrophoresis (CZE) conditions including concentration, pH value and nature (complexing or non-complexing) of the running buffer with or without the addition of methanol, capillary temperature and applied voltage, were studied in order to optimize the separation and resolution of a mixture of 13 C-glycosylflavones and one flavone O-glucoside. Factors primarily responsible for differences in electrophoretic mobility of flavone C-glycosides are identical to those defined from the separation of flavonoid O-glycosides, i.e. number and position of the free hydroxy groups on the flavone skeleton, and number and type of attached sugar groups. Nevertheless, an increase in the pH value from 9 to 10 of the borate running buffer affects the elution order: such an increase induces greater relative electrophoretic mobilities of C-glycoside derivatives with a free hydroxy group at C-4′ compared with those of luteolin C-glycoside derivatives. This change in the migration order could be explained both by a decrease of the net charge linked to an increase and stability of the borate–luteolin complexation and by an increase in molecular size. Moreover the 6-C-glycosylflavones present electrophoretic mobilities lower than their homologous 8-C-glucosyl isomers. Finally, the study of C-glucosylflavones from 18 different samples of Passiflora incarnata by CZE shows a great variability in the qualitative composition. Copyright © 2000 John Wiley & Sons, Ltd.

External lipophilic methylated flavonoids have been extracted from dried leaves of Mentha aquatica, M. spicata, M. x piperita and M. citrata. After separation and purification, twenty flavonoids have been identified by means of spectrometric methods (UV, EIMS, 1H NMR). The flavonoid patterns of these species and hybrid support the view that M. x piperita may be a hybrid of M. aquatica and M. spicata while a linalool-producing sample of M. citrata may be considered a variety of M. aquatica. Cytological data agree with the observed biochemical results.

Different steps of monoterpene metabolism—disappearance of limonene, accumulation of 1,8-cineole, reduction of menthone to menthol and acetylation of menthol—have been studied in different parts of Mentha × piperita leaves of different ages. The analyses of different samples (leaf strips, disks and individual peltate trichomes, translucent or containing crystals from either epidermis) show that all these dynamic changes start at the distal extremity of the leaf and shift progressively towards the base. Except for the peltate trichomes localized within the leaf area, in which a metabolic step is being realized, the trichomes of other parts present a homogeneous monoterpene composition. The measurements of amounts of chlorophyll in two parts, distal and basal, of youngest leaves of terminal buds show that chlorophyll biosynthesis starts also at the distal extremity of the leaf. The regulation of the menthone reduction is discussed.

From the aerial part of Thymus hirtus, eight flavonoids were extracted. Besides three common flavones, apigenin, luteolin and diosmetin, three derivatives of these flavones and two derivatives of quercetin and kaempferol, substituted by a p-hydroxybenzyl moiety, were isolated. The 8-C-substitution of apigenin, luteolin, diosmetin and quercetin was demonstrated by spectrometric data.

A qualitative study of free aglycones from one clone of Mentha × piperita growing natura carried out weekly for 2 months shows that the flavonoid pattern of the whole plant remained invariable. Moreover, the flavonoid composition of mint clones possessing different terpenoid patterns have been studied. A Principal Component Analysis recognizes three flavonoid groups which correspond to the three terpenoid groups. The study of the effects of photoperiodic treatments shows that the flavonoid pattern is affected by the day length.

International audience; In our continual course toward the valorization of traditionally used endemic flora through the analysis of its chemobiodiversity, the phytochemical analysis of aerial parts of Marrubium deserti de Noé was undertaken. Dichloromethane and methanol extracts led to the isolation of terpenoid derivatives among which two were new labdane diterpenes named marrulibacetal A and desertine, respectively. Six of them were known compounds (a mixture of the isomers cyllenin A and 15-epi-cyllenin A, marrubiin, marrulactone, marrulibacetal and β-stigmasterol) and seven known phenolic compounds were also isolated: apigenin and several 7-O-substituted derivatives (apigenin-7-O-β-neohesperidoside, apigenin-7-O-glucoside, terniflorin and apigenin-7-O-glucuronide) together with two phenylethanoid glucosides (acteoside and forsythoside B). The structures and relative configurations of the new compounds were elucidated by MS and a series of 1D and 2D NMR analyses. Some pure compounds have been evaluated for their antioxidant activities through different methods: DPPH and ABTS assays as well as CUPRAC assay. Genotoxic and antigenotoxic activities of extracts and pure compounds were also evaluated in vitro on Escherichia coli PQ37 cells by the SOS Chromotest. Some of the isolated compounds like phenylethanoid derivatives showed stronger antioxidant capacity than trolox and were also able to significantly inhibit β-galactosidase induction caused by the mutagen agent nitrofurantoin.

Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relationships. Decreasing polarity enhanced the binding affinity for the P-glycoprotein C-terminal cytosolic domain since DMA derivatives were more active, but unsubstituted hydroxyl group close to the carbonyl was required for efficient activity.Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relationships. Decreasing polarity enhanced the binding affinity for the P-glycoprotein C-terminal cytosolic domain since DMA derivatives were more active, but unsubstituted hydroxyl group close to the carbonyl was required for efficient activity.

International audience; Four new xanthones, butyraxanthones A?D (1?4), were isolated from the stem bark of Pentadesma butyracea, together with six known xanthones (5?10) and a triterpenoid (lupeol). The structures of 1?4 were established by spectroscopic methods. Compounds 1?10 were tested in vitro for antiplasmodial activity against a Plasmodium falciparum chloroquine-resistant strain and for cytotoxicity against a human breast cancer cell line (MCF-7). Nearly all of these xanthones exhibited good antiplasmodial activity, and some of them also demonstrated potent cytotoxicity. Four new xanthones, butyraxanthones A?D (1?4), were isolated from the stem bark of Pentadesma butyracea, together with six known xanthones (5?10) and a triterpenoid (lupeol). The structures of 1?4 were established by spectroscopic methods. Compounds 1?10 were tested in vitro for antiplasmodial activity against a Plasmodium falciparum chloroquine-resistant strain and for cytotoxicity against a human breast cancer cell line (MCF-7). Nearly all of these xanthones exhibited good antiplasmodial activity, and some of them also demonstrated potent cytotoxicity.

From the dichloromethane extract of aerial parts of Ferula vesceritensis (Apiaceae), 11 sesquiterpene derivatives were isolated. Among them five were compounds designated as 10-hydroxylancerodiol-6-anisate, 2,10-diacetyl-8-hydroxyferutriol-6-anisate, 10-hydroxylancerodiol-6-benzoate, vesceritenone and epoxy-vesceritenol. The six known compounds were identified as feselol, farnesiferol A, lapidol, 2-acetyl-jaeschkeanadiol-6-anisate, lasidiol-10-anisate and 10-oxo-jaesckeanadiol-6-anisate. All the structures were determined by extensive spectroscopic studies including 1D and 2D NMR experiments and mass spectroscopy analysis. Two of the compounds, the sesquiterpene coumarins farnesiferol A and feselol, bound to the model recombinant nucleotide-binding site of an MDR-like efflux pump from the enteropathogenic protozoan Cryptosporidium parvum.

Two new flavonol glycosides: 4′-methylquercetagetin 7-O-(6″-E- caffeoyl-β- d -glucoside ) and quercetagetin 7-O-(6- acetyl-β- d -glucoside ) along with the 7- O -glucosides of 6-hydroxykaempferol, quercetin and quercetagetin have been isolated and characterized from the leaves of Eupatorium glandulosum .

In Mentha x piperita leaves, the peltate glands may be divided into two types according to the presence or the absence of crystals in the head of the trichomes. In both types, the free lipophilic flavonoid aglycones, characterized by UV and chromatographic data, are located in the head of the peltate glands, together with monoterpenes.

Previous studies have shown that flavones bind to P-glycoprotein (Pgp) with higher affinity than isoflavones, flavanones, and glycosylated derivatives. In the present work, a series of C- or O-substituted hydrophobic derivatives of chrysin were synthesized to further investigate structural requirements of the A ring toward Pgp modulation. Increasing hydrophobicity at either position 6, 8, or 7 increased the affinity of in vitro binding to a purified cytosolic domain of Pgp, but only benzyl and 3,3-dimethylallyl C-substitution produced a high maximal quenching of the protein intrinsic fluorescence. Inhibition of membrane Pgp within leukemic cells, characterized by intracellular drug accumulation, was specifically produced by isoprenylated derivatives, with 8-(3,3-dimethylallyl)chrysin being even more efficient than the commonly used cyclosporin A.

Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relationships. Decreasing polarity enhanced the binding affinity for the P-glycoprotein C-terminal cytosolic domain since DMA derivatives were more active, but unsubstituted hydroxyl group close to the carbonyl was required for efficient activity.

The genus Ammoides (Apiaceae) tribe of Ammineae includes two species in Algeria, one of which is endemic: Ammoides atlantica (Coss. et Dur.) Wolf; the other one, Ammoides pusilla (Brot.) Breistr, is widespread in the Mediterranean region [1]. The aerial parts of Ammoides atlantica were collected from Megress Mountain (Eastern Algeria) at 1500 m above sea level during June 2004 and identified by Dr. H. Laouer. A voucher specimen (B6308) has been deposited in the Museum d’Histoire Naturelle of Nice (France). The air-dried powdered parts (700 g) of A. atlantica were macerated three times in boiling methanolic solution (70%). The MeOH extract was concentrated to dryness, the residue was dissolved in boiling water (600 mL) after filtration, and the residue was extracted successively three times with AcOEt and n-butanol (3×200 mL) to give 2.5 and 22.7 g of the respective residues. Solvents were evaporated and the residues of n-BuOH and AcOEt extracts were dissolved in small volumes of MeOH. Analysis by two-dimensional paper chromatography using 15% AcOH and BAW (n-BuOH–AcOH–H2O, 4:1:5, upper phase) as solvents indicated that extracts of n-BuOH and AcOEt contain identical separation of flavonoids. The AcOEt extract was applied to a column of silica gel and eluted with a gradient of n-hexane–AcOEt–MeOH with increasing polarity to obtain nine fractions (A-I). Concentration under reduced pressure of fractions B, D, and G gave three precipitates, which were filtered and washed with MeOH to obtain three compounds 1 (10 mg), 2 (32 mg), and 3 (40 mg). Fraction C was purified by preparative TLC on silica gel eluted with n-hexane–AcOEt (2:8) to afford compound 4 (10 mg). Final purification of each compound for spectral analysis was carried out using MeOH over Sephadex LH-20 (Pharmacia Fine Chemicals), prior to UV, MS, and 1H spectral analysis [2, 3]. Hydrolysis of the glycosides 3 and 4 (HCl 0.1 N, 2 h) yielded the sugar residues and the aglycones, all of which were chromatographed with authentic samples. 1H NMR spectra were recorded in CD3OD at 300 MHz. All the structures were in good agreement with literature data. Compound 1, C15H10O5, mp 345°C, identified as apigenin [4]. Compound 2, C15H10O6, mp 330°C, identified as luteolin [5]. Compound 3, C21H20O10, mp 220–222°C identified as apigenin 7-O-glucoside [6]. Compound 4, C21H20O11, mp 239–242°C, identified as luteolin 7-O-glucoside [7]. Only one flavonoid, luteolin 7-O-glucoside [7], has recently been reported from an Egyptian A. pusilla. Compounds 1–4 were isolated for the first time from A. atlantica, and compounds 3, 4 are reported for a second time from a Ammoides species [6, 7]. Compounds 1 and 2 are new for the genus Ammoides.

International audience; From the diethyl ether extracts of the aerial parts of Thymus herba barona, the flavanones eriodictyol,naringenin and the flavones luteolin, sorbifolin, thymusin, cirsiliol, apigenin, sideritoflavone, cirsimaritin, cirsilineol, xanthomicrol, 8-methoxycirsilineol and genkwanin were isolated and characterized. This is the first report of sorbifolin and cirsiliol in the genus Thymus. The distribution of these flavonoids in the seven terpenoid chemotypes of T. herba barona growing in Corsica was studied and the chemotaxonomic implications of this data discussed.

A new flavonol glycoside isolated from the leaves of Eupatorium glandulosum has been characterized as 6-hydroxykaempferol 7-(6″-caffeoylglucoside) by chemical and spectral methods.