Comparison of the Phytochemical Variation of Non-Volatile Metabolites within Mother Tinctures of Arnica montana Prepared from Fresh and Dried Whole Plant Using UHPLC-HRMS Fingerprinting and Chemometric Analysis.

Arnica montana L. has been recognized for centuries as an herbal remedy to treat wounds and promote healing. It also has a long tradition of use in homeopathy. Depending on its medicinal utilization, standardization regulations allow different manufacturing processes, implying different raw materials, such as the whole arnica plant in its fresh or dried state. In this study, an untargeted metabolomics approach with UHPLC-HRMS/MS was used to cross-compare the phytochemical composition of mother tinctures of A. montana that were prepared from either fresh whole plant (fMT) matter or from oven-dried whole plant (dMT) matter. The multivariate data analysis showed significant differences between fMT and dMT. The dereplication of the HRMS and MS/MS spectra of the more discriminant compounds led to annotated quinic acid, dicaffeoyl quinic acids, ethyl caffeate, thymol derivatives and dehydrophytosphingosine, which were increased in fMT, while Amadori rearrangement products (ARP) and methoxyoxaloyl-dicaffeoyl quinic acid esters were enhanced in dMT. Neither sesquiterpene lactones nor flavonoids were affected by the drying process. This is the first time that a sphingosine, ethyl caffeate and ARP are described in A. montana. Moreover, putative new natural products were detected as 10-hydroxy-8,9-epoxy-thymolisobutyrate and an oxidized proline fructose conjugate, for which isolation and full structure elucidation will be necessary to verify this finding.

Cordiasecosides G-J, 9,10-Seco-29-norcycloartane glycosides isolated from Cordia lutea and their antibacterial activities.

Four undescribed secocycloartane monoglycosides (1-4) were isolated from an ethanolic extract of the dry flowers of Cordia lutea Lam. Their structural assignment is based on NMR and MS analysis. Their stereochemistry is confirmed by molecular modelling studies using DFT-NMR calculations done for compound 3. In vitro antibacterial activity of the four compounds was moderate on Helicobacter pylori (MIC = 15.6 µg/mL), and much weaker on Staphylococcus aureus, Pseudomonas aeruginosa or Escherichia coli (MIC >125 µg/mL). Toxicity evaluated against RAW 264.7 cells was weak (IC50 values ranging from 24 to 41 µM i.e. 15 to 24 µg/mL), but in the same range as anti-Helicobacter activity.

Quality assessment of Curcuma dietary supplements: Complementary data from LC-MS and 1H NMR.

Due to the numerous potential health benefits of Curcuma, turmeric dietary supplements (DS) are among the top selling products. To assess the quality of these formulations, thirty Curcuma DS along with five standard Curcuma rhizomes were analyzed with UHPLC-MS and 1H NMR. The chemometric treatment of the UHPLC-MS spectra showed a significant variability of their chemical composition that was confirmed by 1H NMR which allowed the absolute quantification of the Curcuma major bioactive components, i.e. curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin), and turmerones (aryl-, α- and ß-) as well as piperine, a commonly associated curcumin bioavailability enhancer: respectively 3.5-556, 0-8.6, 0.18-8.1 mg/capsule or tablet. The comparison of the actual and claimed quantities of curcuminoids and piperine showed that 58% of the DS contained the expected amounts of actives.

Pharmacological validation of Solanum mammosum L. as an anti-infective agent: Role of solamargine.

ETHNOPHARMACOLOGICAL RELEVANCE: Fungal and bacterial infections remain a major problem worldwide, requiring the development of effective therapeutic strategies. Solanum mammosum L. (Solanaceae) ("teta de vaca") is used in traditional medicine in Peru to treat fungal infections and respiratory disorders via topical application. However, the mechanism of action remains unknown, particularly in light of its chemical composition. MATERIALS AND METHODS: The antifungal activity of TDV was determined against Trichophyton mentagrophytes and Candida albicans using bioautography-TLC-HRMS to rapidly identify the active compounds. Then, the minimum inhibitory concentration (MIC) of the fruit crude extract and the active compound was determined to precisely evaluate the antifungal activity. Additionally, the effects of the most active compound on the formation of Pseudomonas aeruginosa biofilms and pyocyanin production were evaluated. Finally, a LC-HRMS profile and a molecular network of TDV extract were created to characterize the metabolites in the fruits' ethanolic extract. RESULTS: Bioautography-TLC-HRMS followed by isolation and confirmation of the structure of the active compound by 1D and 2D NMR allowed the identification solamargine as the main compound responsible for the anti-Trichophyton mentagrophytes (MIC = 64 µg mL-1) and anti-Candida albicans (MIC = 64 µg mL-1) activities. In addition, solamargine led to a significant reduction of about 20% of the Pseudomonas aeruginosa biofilm formation. This effect was observed at a very low concentration (1.6 µg mL-1) and remained fairly consistent regardless of the concentration. In addition, solamargine reduced pyocyanin production by about 20% at concentrations of 12.5 and 50 µg mL-1. Furthermore, the LC-HRMS profiling of TDV allowed us to annotate seven known compounds that were analyzed through a molecular network. CONCLUSIONS: Solamargine has been shown to be the most active compound against T. mentoagrophytes and C. albicans in vitro. In addition, our data show that this compound affects significantly P. aeruginosa pyocyanin production and biofilm formation in our conditions. Altogether, these results might explain the traditional use of S. mammosum fruits to treat a variety of fungal infections and respiratory disorders.

A Citrullus colocynthis fruit extract acutely enhances insulin-induced GLUT4 translocation and glucose uptake in adipocytes by increasing PKB phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus colocynthis (L.) Schrad is a common fruit in traditional medicine and used as remedy against various diseases, especially diabetes. Up to now, its anti-diabetic effects have been fully attributed to its enhancement of pancreatic insulin secretion. Whether C. colocynthis also ameliorates insulin action in peripheral tissues has not been investigated. AIM OF THE STUDY: In the present study, using 3T3-L1 adipocytes as cell model, we have investigated whether colocynth fruit extracts affect insulin action. MATERIALS AND METHODS: Various extracts were prepared from the C. colocynthis fruit and screened using a cell-based 96 well plate GLUT4 translocation assay. Promising extracts were further studied for their effects on glucose uptake and cell viability. The effect on insulin signal transduction was determined by Western blot and the molecular composition was established by LC-MS. RESULTS: The ethyl acetate fractions of aqueous non-defatted extracts of seed and pulp, designated Sna1 and Pna1, acutely enhanced insulin-induced GLUT4 translocation. In accordance, both extracts increased insulin-stimulated cellular glucose uptake. Pna1, which displayed greater effects on GLUT4 and glucose uptake than Sna1, was further investigated and was demonstrated to increase GLUT4 translocation without changing the half-maximum dose (ED50) of insulin, nor changing GLUT4 translocation kinetics. At the molecular level, Pna1 was found to enhance insulin-induced PKB phosphorylation without changing phosphorylation of the insulin receptor. Pna1 appeared not to be toxic to cells and, like insulin, restored cell viability during serum starvation. By investigating the molecular composition of Pna1, nine compounds were identified that made up 87% of the mass of the extract, one of which is likely to be responsible for the insulin-enhancing effects of Pna1. CONCLUSIONS: The C. colocynthis fruit possesses insulin-enhancing activity. This activity may explain in part its anti-diabetic effects in traditional medicine. It also identifies the C. colocynthis as a source of a potential novel insulin enhancer that may prove to be useful to reduce hyperglycemia in type 2 diabetes.

Structural Characterization and Anti-infective Activity of 9,10-Seco-29-norcycloartane Glycosides Isolated from the Flowers of the Peruvian Medicinal Plant Cordia lutea.

Six new secocycloartane glycosides (1-6) were isolated from the ethanol extract of the flowers of Cordia lutea Lam. on the basis of bioassay-guided fractionation. Their structures were determined by the application of NMR and MS data analyses together with X-ray crystallographic analyses for compounds 1 and 2. Compounds 1-6 represent the first examples of 9,10-seco-29-norcycloartane glycosides. These compounds showed significant in vitro anti-Helicobacter pylori activity, and no activity against either Escherichia coli or Pseudomonas aeruginosa. Significant activity was observed for 5 and 6 against Staphylococcus aureus. All compounds displayed weak cytotoxicity against RAW 264.7 cells. The in vitro antileishmanial and antiplasmodial activities of 1-6 were also evaluated.

Comparison of the Phytochemical Composition of Serenoa repens Extracts by a Multiplexed Metabolomic Approach.

Phytochemical extracts are highly complex chemical mixtures. In the context of an increasing demand for phytopharmaceuticals, assessment of the phytochemical equivalence of extraction procedures is of utmost importance. Compared to routine analytical methods, comprehensive metabolite profiling has pushed forward the concept of phytochemical equivalence. In this study, an untargeted metabolomic approach was used to cross-compare four marketed extracts from Serenoa repens obtained with three different extraction processes: ethanolic, hexanic and sCO2 (supercritical carbon dioxide). Our approach involved a biphasic extraction of native compounds followed by liquid chromatography coupled to a high-resolution mass spectrometry based metabolomic workflow. Our results showed significant differences in the contents of major and minor compounds according to the extraction solvent used. The analyses showed that ethanolic extracts were supplemented in phosphoglycerides and polyphenols, hexanic extracts had higher amounts of free fatty acids and minor compounds, and sCO2 samples contained more glycerides. The discriminant model in this study could predict the extraction solvent used in commercial samples and highlighted the specific biomarkers of each process. This metabolomic survey allowed the authors to assess the phytochemical content of extracts and finished products of S. repens and unequivocally established that sCO2, hexanic and ethanolic extracts are not chemically equivalent and are therefore unlikely to be pharmacologically equivalent.

Profiling of Hura crepitans L. latex by ultra-high-performance liquid chromatography/atmospheric pressure chemical ionisation linear ion trap Orbitrap mass spectrometry.

INTRODUCTION: The phytochemistry of the latex of Hura crepitans L. (Euphorbiaceae), a widespread tree in the Amazonian forest having many uses, is little known. Only huratoxin, a daphnane diterpene orthoester, has been described despite the high pharmacological potential of this kind of compounds. Glucosphingolipids (cerebrosides) are also known to be distributed in Euphorbiaceae latexes. OBJECTIVE: To tentatively identify daphnanes diterpenes and cerebrosides in the latex of H. crepitans. METHODS: An ethanolic extract of the lyophilised latex of H. crepitans was analysed by ultra-high-performance liquid chromatography (UHPLC) coupled with positive and negative atmospheric pressure chemical ionisation high-resolution mass spectrometry (APCI-HRMS) method using a quadrupole/linear ion trap/Orbitrap (LTQ-Orbitrap). Tandem mass spectrometry (MS/MS) spectra were recorded by two different fragmentation modes: collision induced dissociation (CID) and higher-energy collisional dissociation (HCD). RESULTS: The analysis of CID- and HCD-MS/MS spectra allowed to propose fragmentation patterns for daphnane esters and cerebrosides and highlight diagnostic ions in positive and negative ion modes. A total of 34 compounds including 24 daphnane esters and 10 cerebrosides have been tentatively annotated. Among them, 17 daphnane diterpenes bearing one or two acyl chains are new compounds and the cerebrosides are described in the genus Hura for the first time. CONCLUSION: This study revealed the chemical constituents of the latex of H. crepitans and particularly its richness and chemical diversity in daphnane diterpenes, more frequently encountered in the species of Thymelaeaceae.

Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3ß regulation in intestinal cells.

CONTEXT AND OBJECTIVE: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 ß (GSK3ß) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3ß and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3ß. MATERIALS AND METHODS: Methanol extracts from D. harra flowers were prepared and the bio-guided fractionation of their active compounds was performed using inflammatory [protease-activated receptor 2 (PAR2)-stimulated IEC6 cells] and cancer (human Caco-2 cell line) intestinal cells. 50-100 µg/mL of fractions or compounds purified by HPLC were incubated with cells whose inhibited form of GSK3ß (Pser9 GSK3ß) and survival were analyzed by Western blot at 1 h and colorimetric assay at 24 h, respectively. LC-UV-MS profiles and MS-MS spectra were used for the characterization of extracts and flavonoids-enriched fractions, and the identification of pure flavonoids was achieved by MS and NMR analysis. RESULTS: The methanol extract from D. harra flowers and its flavonoid-enriched fraction inhibit GSK3ß in PAR2-stimulated IEC6 cells. GSK3ß inhibition by the flavonoid-enriched D. harra fraction was dependent on PKC activation. The flavonoid-enriched D. harra fraction and its purified compound isorhamnetin-3,7-di-O-glucoside induced a 20% decrease of PAR2-stimulated IEC6 and Caco-2 cell survival. Importantly, normal cells (non-stimulated IEC6 cells) were spared by these treatments. CONCLUSION: This work indicates that flavonoids from D. harra display cytotoxic activity against inflammatory and cancer intestinal cells which could depend on GSK3ß inhibition.

Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad.

Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an ethyl acetate extract of Citrullus colocynthis leaves together with four known cucurbitacins. Their structures were established on the basis of their spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro cytotoxic activity of the isolated compounds against two human colon cancer cell lines (HT29 and Caco-2) and one normal rat intestine epithelial cell line (IEC6), revealed that one of the isolated compounds presented interesting specific cytotoxic activity towards colorectal cell lines.

Evaluation of antiplasmodial and antileishmanial activities of herbal medicine Pseudelephantopus spiralis (Less.) Cronquist and isolated hirsutinolide-type sesquiterpenoids.

ETHNOPHARMACOLOGICAL RELEVANCE: Pseudelephantopus spiralis (Less.) Cronquist is distributed in the Caribbean, Mesoamerica and Latin America. Preparations of the plant are traditionally used in Latin America for the treatment of various diseases including fever, malaria, and spleen or liver inflammations. MATERIALS AND METHODS: Aerial parts of P. spiralis were extracted with either ethanol or distilled water. Seven hirsutinolide-type sesquiterpenoids were isolated: 8-acetyl-13-ethoxypiptocarphol (1), diacetylpiptocarphol (2), piptocarphins A (3), F (4) and D (5), (1S(*),4R(*),8S(*),10R(*))-1,4-epoxy-13-ethoxy-1,8,10-trihydroxygermacra-5E,7(11)-dien-6,12-olide (6), and piptocarphol (7). Extracts and isolated compounds (2, 3, 5-7) were screened for their in vitro antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum strain FcM29-Cameroon and antileishmanial activity against three stages of Leishmania infantum. Their cytotoxicities were also evaluated against healthy VERO cell lines and J774A.1 macrophages, the host cells of the Leishmania parasites in humans. RESULTS: Aqueous extracts showed a greater inhibitory effect than alcoholic extracts, with IC50 on P. falciparum of 3.0µg/mL versus 21.1µg/mL, and on L. infantum of 13.4µg/mL versus >50µg/mL. Both extracts were found to be cytotoxic to VERO cells (CC50<3µg/mL). Sesquiterpene lactones 2 and 3 showed the best activity against both parasites but failed in selectivity. Carbon 8 hydroxylated hirsutinolides 5-7 presented the particularity of exhibiting two conformers observed in solution during extensive NMR analyses in CD3OD and UHPLC-MS. The presence of a hydroxyl function at C-8 decreased the activity of 5-7 on the two parasites and also on VERO cells. CONCLUSION: The antiplasmodial activity displayed by the aqueous extract explains the traditional use of P. spiralis in the treatment of malaria. This activity seems to be attributable to the presence of sesquiterpene lactones 2 and 3, the most active against P. falciparum. Aqueous extract and compounds 2, 3 and 6 were also active against L. infantum but lacked in selectivity due to their cytotoxicity towards macrophages. Exploring the safety and antiplasmodial efficacy of this traditional remedy will require further toxicological and in vivo studies in the light of the cytotoxicity towards healthy cell lines displayed by the aqueous extract and compounds 2 and 3.

Development and validation of liquid chromatography combined with tandem mass spectrometry methods for the quantitation of simalikalactone E in extracts of Quassia amara L. and in mouse blood.

INTRODUCTION: Simalikalactone E (SkE) from Quassia amara, has been proved to be a valuable anti-malarial and anti-cancer compound. As SkE is very scarce, methods of quantitation are needed in order to optimise its isolation process and to determine pharmacokinetic data. OBJECTIVE: To validate methods using liquid chromatography coupled to mass spectrometry for the quantitation of SkE in plant extracts and in biological fluids. METHODS: High- and ultrahigh-performance liquid chromatography (UHPLC) coupled to ion trap mass spectrometry (MS) with single ion monitoring detection and to triple quadrupole-linear ion trap tandem mass spectrometry with multiple reaction monitoring detection methods were developed. Validation procedure was realised according to the International Conference on Harmonisation guideline. Methanol extracts of dried Quassia amara leaves, and mouse-blood samples obtained after various routes of administration, were analysed for SkE. RESULTS: Methods were validated and gave similar results regarding the content of SkE expressed per kilogram of dry leaves in the traditional decoction (160 ± 12 mg/kg) and in the methanol extract (93 ± 2 mg/kg). The recovery of the analyte from mouse blood ranged from 80.7 to 119.8%. Simalikalactone E was only detected using UHPLC-MS/MS (0.2 ± 0.03 mg/L) in mouse blood after intravenous injection: none was detected following intraperitoneal or oral gavage administration of SkE. CONCLUSION: The LC-MS methods were used for the quantitation of SkE in plant extracts and in mouse blood. These methods open the way for further protocol optimisation of SkE extraction and the determination of its pharmacokinetic data.

Leishmanicidal compounds and potent PPARγ activators from Renealmia thyrsoidea (Ruiz & Pav.) Poepp. & Endl.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves and rhizomes of Renealmia thyrsoidea (Ruiz & Pav.) Poepp. & Endl. traditionally used in the Yanesha pharmacopoeia to treat skin infections such as leishmaniasis ulcers, or to reduce fever were chemically investigated to identify leishmanicidal compounds, as well as PPARγ activators. METHODS: Compounds were isolated through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The viability of Leishmania amazonensis axenic amastigotes was assessed by the reduction of tetrazolium salt (MTT), the cytotoxicity on macrophage was evaluated using trypan blue dye exclusion method, while the percentage of infected macrophages was determined microscopically in the intracellular macrophage-infected assay. The CD36, mannose receptor (MR) and dectin-1 mRNA expression on human monocytes-derived macrophages was evaluated by quantitative real-time PCR. RESULTS: Six sesquiterpenes (1-6), one dihydrobenzofuranone (7) and four flavonoids (8-11) were isolated from the leaves. Alongside, two flavonoids (12-13) and five diarylheptanoids (14-18) were identified in the rhizomes. Leishmanicidal activity against Leishmania amazonensis axenic amastigotes was evaluated for all compounds. Compounds 6, 7, and 11, isolated from the leaves, showed to be the most active derivatives. Diarylheptanoids 14-18 were also screened for their ability to activate PPARγ nuclear receptor in macrophages. Compounds 17 and 18 bearing a Michael acceptor moiety strongly increased the expression of PPARγ target genes such as CD36, Dectin-1 and mannose receptor (MR), thus revealing interesting immunomodulatory properties. CONCLUSIONS: Phytochemical investigation of Renealmia thyrsoidea has led to the isolation of leishmanicidal compounds from the leaves and potent PPARγ activators from the rhizomes. These results are in agreement with the traditional uses of the different parts of Renealmia thyrsoidea.

Macrocyclic spermidine alkaloids from Androya decaryi L. Perrier.

Three new spermidine alkaloids and two known compounds were isolated from the leaves of Androya decaryi. Their structures were elucidated on the basis of their spectroscopic data (NMR and mass spectrometry), by X-Ray diffraction and by comparison with literature values. Evaluation of the in vitro antiplamosdial properties of the isolated compounds revealed they did not possess any significant activity.

Dihydrochalcones and benzoic acid derivatives from Piper dennisii.

Two new dihydrochalcones (1, 2), as well as eight known compounds, piperaduncin C (3), 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), 4,2',6'-trihydroxy-4'-methoxydihydrochalcone (5), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (6), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (7), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid (8), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2H-1-chromene-6-carboxylic acid (9), and 3-(3',7'-dimethyl-2',6'-octadienyl)-4-methoxybenzoic acid (10) were isolated from the leaves of Piper dennisii Trelease (Piperaceae), using a bioassay-guided fractionation to determine their antileishmanial potential. Among them, compound 10 exhibited the best antileishmanial activity (IC50 = 20.8 µM) against axenic amastigote forms of Leishmania amazonensis, with low cytotoxicity on murine macrophages. In the intracellular macrophage-infected model, compound 10 proved to be more active (IC50 = 4.2 µM). The chemical structures of compounds 1-10 were established based on the analysis of the spectroscopic data.

A review of traditional remedies of ciguatera fish poisoning in the Pacific.

Ciguatera fish poisoning (CFP) is an illness caused by eating tropical coral fish contaminated with ciguatoxins (CTXs). The clinical management of patients with CFP is generally supportive and symptomatic in nature as no antidote exists. Of the many drugs prescribed, several have been claimed to be efficient in small, uncontrolled studies, but the outcomes of treatments with these medicines are often contradictory. In New Caledonia, traditional remedies are commonly employed in the treatment of CFP and of the 90 plant species catalogued as useful in CFP, the most popular herbal remedy by far is a decoction prepared from the leaves of Heliotropium foertherianum Diane & Hilger (Boraginaceae). Other important plants used in the treatment of CFP include Euphorbia hirta L. (Euphorbiaceae) and Vitex L. sp. (Lamiaceae). This review focuses on the evidence for efficacy of these species and pharmacological studies which support their use. Other plants used in CFP and the conventional treatment of CFP are also discussed briefly.

Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells.

In search for compounds able to reduce cell adhesion-mediated drug resistance (CAM-DR), we studied effects of Hammada scoparia extracts on leukemic cells adherent or in suspension. We show that H. scoparia flavonoidic fraction and its compound rutin induce apoptosis specifically in adherent leukemic cells and abolish CAM-DR. Importantly, rutin inhibited survival of adherent leukemic progenitors (CD34(+)38(-)123(+)) but spared normal progenitors (CD34(+)38(-)). The pro-apoptotic effects of rutin were correlated with a decrease of active GSK3ß and inhibitors of GSK3ß reproduced rutin-induced cytotoxicity. This study uncovers the potential of H. scoparia flavonoids and rutin to overcome CAM-DR in acute myeloid leukemia.

Application of toxicogenomic tools in the drug research and development process.

The cost for the development of new active and safe drugs is higher than ever and continues to increase. At the same time, both the pharmaceutical industry and the Regulatory Authorities are, despite the increasing effort to develop safer drugs, concerned by the risk of unexpected side effects observed in the late steps of the development of new drugs, either in late clinical development or after marketing approval. Then, the early knowledge of any potential toxic effect of a new drug is a key issue to allow adequate decision making. This means that current approaches based on the determination of the No-Adverse-Effect-Level and the Human-Equivalent-Dose are far from being perfect, and fail mainly to detect toxic phenomena of low intensity and/or low frequency. To improve the predictability of the existing experimental models, Toxicogenomics could be included into the in vitro candidate-selection steps and/or during the regulatory preclinical (or clinical) studies. In this communication, the authors present an example of the use of Toxicogenomic data to support decision making when selecting a new candidate to regulatory development. The authors also present a second example of integration of Toxicogenomics with the animal regulatory studies within the preclinical development of a new drug.

Cytotoxic and antiplasmodial xanthones from Pentadesma butyracea.

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 anti-protozoal and anti-bacterial compounds from Tapirira guianensis.

Tapirira guianensis is a common tree used in traditional medicine in French Guiana against several infectious diseases (malaria, leishmaniasis, bacteria, etc.). The bioassay-guided purification of CH(2)Cl(2) bark extract led to the isolation of four cyclic alkyl polyol derivatives: 4,6,2'-trihydroxy-6-[10'(Z)-heptadecenyl]-1-cyclohexen-2-one (1a), 1,4,6-trihydroxy-1,2'-epoxy-6-[10'(Z)-heptadecenyl]-2-cyclohexene (1b), 1,4,5,2'-tetrahydroxy-1-[10'(Z)-heptadecenyl]-2-cyclohexene (2), and 1,3,4,6-tetrahydroxy-1,2'-epoxy-6-[10'(Z)-heptadecenyl]-cyclohexane (3). The structures were established on the basis of 1D and 2D NMR analyses. The anti-leishmanial, anti-plasmodial, anti-bacterial (on Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli), and anti-fungal (on Candida albicans) activities of the extracts and of these original compounds were evaluated. Two showed medicinal interest supporting the traditional uses of the plant. The structures were established through spectral analyses of the isolates and their derivatives.