Antibacterial and anti-coronavirus investigation of selected Senegalese plant species according to an ethnobotanical survey.

ETHNOPHARMACOLOGICAL RELEVANCE: In Senegal, upper and lower respiratory tract infections constitute a real health problem. To manage these disorders, most people rely on the use of local medicinal plants. This is particularly the case for species belonging to the botanical families, Combretaceae, Fabaceae, Myrtaceae and Rubiaceae, which are widely used to treat various respiratory problems such as colds, flu, rhinitis, sinusitis, otitis, angina, bronchitis, bronchiolitis and also pneumonia. AIM OF THE STUDY: The aim of this study was to identify medicinal plants traditionally used for the management of infectious diseases, in particular those of the respiratory tract. On the basis of these ethnopharmacological uses, this study made it possible to highlight the antibacterial, antiviral and cytotoxic activities of selected plant species. MATERIALS AND METHODS: An ethnobotanical survey was conducted in Senegal among informants, including herbalists, traditional healers, and households, using medicinal plants in the management of infectious diseases, with a focus on respiratory tract infections. The most cited plant species were evaluated in vitro on a panel of 18 human pathogenic bacteria may be involved in respiratory infections and against the human coronavirus HCoV-229E in Huh-7 cells. The antiviral activity of the most active extracts against HCoV-229E was also evaluated on COVID-19 causing agent, SARS-CoV-2 in Vero-81 cells. In parallel, cytotoxic activities were evaluated on Huh-7 cells. RESULTS: A total of 127 informants, including 100 men (78.74%) and 27 women (21.26%) participated in this study. The ethnobotanical survey led to the inventory of 41 plant species belonging to 19 botanical families used by herbalists and/or traditional healers and some households to treat infectious diseases, with a specific focus on upper respiratory tract disorders. Among the 41 plant species, the most frequently mentioned in the survey were Guiera senegalensis J.F. Gmel. (95.2%), Combretum glutinosum Perr. Ex DC. (93.9%) and Eucalyptus spp. (82.8%). Combretaceae (30.2%) represented the most cited botanical family with six species, followed by Fabaceae (29.3%, 12 species). A total of 33 crude methanolic extracts of the 24 plant species selected for their number of citations were evaluated in vitro for their antimicrobial and cytotoxic activities. Guiera senegalensis, Combretum glutinosum, Vachellia nilotica subsp. tomentosa (Benth.) Kyal. & Boatwr, Eucalyptus camaldulensis Dehnh., and Terminalia avicennioides Guill. & Perr., showed antibacterial activities. The most active plants against HCoV-229E were: Ficus sycomorus L., Mitragyna inermis (Willd.) Kuntze, Pterocarpus erinaceus Poir., and Spermacoce verticillata L. One of these plants, Mitragyna inermis, was also active against SARS-CoV-2. CONCLUSION: This work confirmed the anti-infective properties of plant species traditionally used in Senegal. Overall, the most frequently cited plant species showed the best antibacterial activities. Moreover, some of the selected plant species could be considered as a potential source for the management of coronavirus infections. This new scientific data justified the use of these plants in the management of some infectious pathologies, especially those of the respiratory tract.

Deciphering anti-infectious compounds from Peruvian medicinal Cordoncillos extract library through multiplexed assays and chemical profiling.

High prevalence of parasitic or bacterial infectious diseases in some world areas is due to multiple reasons, including a lack of an appropriate health policy, challenging logistics and poverty. The support to research and development of new medicines to fight infectious diseases is one of the sustainable development goals promoted by World Health Organization (WHO). In this sense, the traditional medicinal knowledge substantiated by ethnopharmacology is a valuable starting point for drug discovery. This work aims at the scientific validation of the traditional use of Piper species ("Cordoncillos") as firsthand anti-infectious medicines. For this purpose, we adapted a computational statistical model to correlate the LCMS chemical profiles of 54 extracts from 19 Piper species to their corresponding anti-infectious assay results based on 37 microbial or parasites strains. We mainly identified two groups of bioactive compounds (called features as they are considered at the analytical level and are not formally isolated). Group 1 is composed of 11 features being highly correlated to an inhibiting activity on 21 bacteria (principally Gram-positive strains), one fungus (C. albicans), and one parasite (Trypanosoma brucei gambiense). The group 2 is composed of 9 features having a clear selectivity on Leishmania (all strains, both axenic and intramacrophagic). Bioactive features in group 1 were identified principally in the extracts of Piper strigosum and P. xanthostachyum. In group 2, bioactive features were distributed in the extracts of 14 Piper species. This multiplexed approach provided a broad picture of the metabolome as well as a map of compounds putatively associated to bioactivity. To our knowledge, the implementation of this type of metabolomics tools aimed at identifying bioactive compounds has not been used so far.

Antimicrobial Properties of Compounds Isolated from Syzygium malaccense (L.) Merr. and L.M. Perry and Medicinal Plants Used in French Polynesia.

A preliminary ethnopharmacological survey, achieved in French Polynesia, led to the collection of the most cited plants among 63 species used to treat "infectious" diseases, with a description of their medicinal uses. Bibliographical investigations and antimicrobial screening permitted the selection of the botanical species Syzygium malaccense (Myrtaceae) for phytochemical analysis. Leaves of Syzygium malaccense were usually used in mixture with rhizomes of Curcuma longa to treat infectious diseases such as cystitis. The methanolic plant extracts were tested in vitro with an agar microdilution method on 33 bacteria strains and 1 yeast to obtain their Minimal Inhibitory Concentration (MIC), and cytotoxicity against HepG2 cells were evaluated. Antimicrobial synergistic effects of methanolic plant extracts from leaves of Syzygium malaccense and rhizomes from Curcuma longa were also evaluated. The bio-guided isolation of leaf extract from Syzygium malaccense led to the identification of seven alkyl-salicylic acids (anacardic acids or ginkgolic acids C15:0, C15:1, C17:0, C17:1, C17:2, C17:3 and C19:1) described for the first time in this species. All compounds were tested against Staphylococcus aureus (18.75 < MIC < 75.0 µg/mL), Streptococcus pyogenes (2.34 < MIC < 18.75 µg/mL) and Pseudomonas aeruginosa (MIC = 150 µg/mL), and their structure−activity relationships were discussed. The methanolic extract and salicylic derivatives from S. malaccense showed an interesting antimicrobial activity against Gram+ bacteria, without toxicity on hepG2 cells at 400 µg/mL. Moreover, these antibacterial compounds have already been studied for their anti-inflammatory activity, which supports the therapeutic interest of S. malaccense against infectious diseases.

Anti-HCV Tannins From Plants Traditionally Used in West Africa and Extracted With Green Solvents.

Millions of people are still infected with hepatitis C virus (HCV) nowadays. Although recent antivirals targeting HCV proteins are very efficient, they are not affordable for many people infected with this virus. Therefore, new and more accessible treatments are needed. Several Ivorian medicinal plants are traditionally used to treat "yellow malaria", a nosological category including illness characterized by symptomatic jaundice such as hepatitis. Therefore, some of these plants might be active against HCV. An ethnobotanical survey in Côte d'Ivoire allowed us to select such medicinal plants. Those were first extracted with methanol and tested for their anti-HCV activity. The most active ones were further studied to specify their IC50 and to evaluate their toxicity in vitro. Greener solvents were tested to obtain extracts with similar activities. Following a phytochemical screening, tannins of the most active plants were removed before re-testing on HCV. Some of these tannins were identified by UPLC-MS and pure molecules were tested against HCV. Out of the fifteen Ivorian medicinal plants selected for their putative antiviral activities, Carapa procera DC. and Pericopsis laxiflora (Benth. ex Baker) Meeuwen were the most active against HCV (IC50: 0.71 and 0.23 µg/ml respectively) and not toxic for hepatic cells. Their crude extracts were rich in polyphenols, including tannins such as procyanidins A2 which is active against HCV. The same extracts without tannin lost their anti-HCV activity. Replacing methanol by hydro-ethanolic solvent led to tannins-rich extracts with similar antiviral activities, and higher than that of aqueous extracts.

Viral hepatitis in the Peruvian Amazon: Ethnomedical context and phytomedical resource.

ETHNOPHARMACOLOGICAL RELEVANCE: An extensive ethnopharmacological survey was carried out in the Peruvian Amazonian district of Loreto with informants of various cultural origins from the surroundings of Iquitos (capital city of Loreto) and from 15 isolated riverine Quechua communities of the Pastaza River. A close attention was paid to the medical context and plant therapy, leading to the selection of 35 plant species (45 extracts). The extracts were tested for antiviral activity against HCV with counting of Huh-7 cellular death in case of toxicity, and cytotoxicity was evaluated in HepG2 cells. AIM OF THE STUDY: The aim of the study was to inventory the plants used against hepatitis in Loreto, then to evaluate their antiviral activity and to suggest a way to improve local therapeutic strategy against viral hepatitis, which is a fatal disease that is still increasing in this area. MATERIALS AND METHODS: An ethnographic survey was carried out using "participant-observation" methodology and focusing on plant therapy against hepatitis including associated remedies. 45 parts of plant were extracted with methanol and tested in vitro for anti-HCV activity in 96-well plate, using HCV cell culture system with immunofluorescent detection assisted by automated confocal microscopy. Toxicity of plant extracts was also evaluated in microplates on hepatic cells by immunofluorescent detection, for the Huh-7 nuclei viability, and by UV-absorbance measurement of MTT formazan for cytotoxicity in HepG2 cells. RESULTS: In vitro assay revealed interesting activity of 18 extracts (50% infection inhibition at 25 µg/mL) with low cytotoxicity for 15 of them. Result analysis showed that at least 30% of HCV virus were inhibited at 25 µg/mL for 60% of the plant extracts. Moreover, the ethnomedical survey showed that remedies used with low and accurate dosing as targeted therapy against hepatitis are usually more active than species indicated with more flexible dosing to alleviate symptoms of hepatic diseases. CONCLUSION: Together with bibliographic data analysis, this study supported the traditional medicinal uses of many plants and contributed to a better understanding of the local medical system. It also permitted to refine the therapeutic plant indications regarding patients' liver injuries and vulnerability. Only 2 of the 15 most active plant species have already been studied for antiviral activity against hepatitis suggesting new avenues to be followed for the 13 other species.

Antimicrobial and Light-Enhanced Antimicrobial Activities, Cytotoxicity and Chemical Variability of All Tunisian Eryngium Species.

This study was performed on all Eryngium species growing in Tunisia in order to evaluate their intra and interspecies variabilities and to investigate their biological activities. These species are used in traditional medicine, and literature about the phytochemical investigations of most of them is scarce. Antimicrobial and light-enhanced activities were tested against multiresistant microorganisms and extended spectrum beta-lactamase producing bacteria (ESBL). All studied species showed antimicrobial effect with several MIC values lower than 70 µg/ml. Tested Eryngium species have proven to be a promising source of photoactive compounds, while light-enhanced activity offers an alternative for the inactivation of pathogenic microorganisms which is currently subjected to a great interest. This is the first report of this activity in genus Eryngium. A significant improvement of antimicrobial activity with UV irradiation was observed, mainly for E. dichotomum, E. ilicifolium and E. triquetrum. Cytotoxicity, studied for the first time for the most species, was evaluated against cancer (J774) and non-cancer (WI38) human cell lines. Chemical composition of volatile compounds presented in the most active crude extracts (petroleum ether extracts) of the aerial parts was investigated using GC/MS analysis and was submitted to statistical analyses. It revealed their high content of bioactive phytochemicals, particularly oxygenated sesquiterpenes like spathulenol, ledol and α-bisabolol but also hydrocarbon sesquiterpenes such as ß-bisabolene and copaene, as well as polyacetylene derivatives such as falcarinol. Statistical analyses permitted to evaluate the interrelations between all Tunisian Eryngium species.

Plant therapy in the Peruvian Amazon (Loreto) in case of infectious diseases and its antimicrobial evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant species reported here are used in contemporary phytotherapies by native and neo-urban societies from the Iquitenian surroundings (district of Loreto, Peruvian Amazon) for ailments related to microbial infections. Inhabitants of various ethnic origins were interviewed and 81 selected extracts were evaluated for their antimicrobial properties against a panel of 36 sensitive and multi-resistant bacteria or yeast. Medicinal plant researches in the Peruvian Amazon are now significant, but none of them has focused on an exhaustive listing of identified species tested on so many microbes with standardized experiments (to obtain MIC value). AIM OF THE STUDY: The aim of the study was to inventory the plants used against infections in the Loreto, an Amazonian region of Peru. It led to the new identification of secondary metabolites in two plant species. MATERIALS AND METHODS: Ethnographic survey was carried out using "participant-observation" methodology and focus on bioprospecting of antimicrobial remedies. Selected plant extracts and antimicrobial drugs were tested in vitro with agar dilution method on 35 bacteria strains and 1 yeast to evaluate their Minimal Inhibitory Concentration (MIC). Microdilution methods using 96-well microtiter plates were used for the determination of MIC from isolated compounds, and cytotoxicity in HepG2 cells from some selected extracts were also evaluated. Activity-guided isolation and identification of compounds were performed by various chromatographic methods and structural elucidations were established using HRMS and NMR spectroscopy. RESULTS: This study outlined antimicrobial activities of 59 plant species from 33 families (72 single plant extracts and 2 fermented preparations), 7 mixtures, and one insect nest extract against 36 microorganisms. Of the 59 species analysed, 12 plants showed relevant antibacterial activity with MIC ≤0.15 mg/mL for one or several of the 36 micro-organisms (Aspidosperma excelsum, Brosimum acutifolium, Copaifera paupera, Erythrina amazonica, Hura crepitans, Myrciaria dubia, Ocotea aciphylla, Persea americana, Spondias mombin, Swartzia polyphylla, Virola pavonis, Vismia macrophylla). Examination by bioautography of E. amazonica, M. dubia and O. aciphylla extracts allowed the phytochemical characterization of antimicrobial fractions and compounds. CONCLUSION: This study suggested an a posteriori correlation of the plant extract antimicrobial activity with the chemosensory cues of the drugs and attested that those chemosensory cues may be correlated with the presence of antimicrobial compounds (alkaloids, tannins, saponosids, essential oil, oleoresin …). It also led to the first isolation and identification of three secondary metabolites from E. amazonica and M. dubia.

Aqueous extracts of Syzygium brazzavillense can inhibit the infection with coxsackievirus B4 in vitro.

Traditional practitioners commonly use plant crude extracts to treat various diseases in patients with symptoms that can be seen during enterovirus infections. In this study, the antienteroviral activity of medicinal plants from the Republic of Congo has been evaluated in vitro. Through an ethnopharmacological approach, seven plants grouped into six families were identified. Aqueous and organic extracts of various organs from these plants were prepared. The organic extracts at subcytotoxic concentrations did not inhibit the cytopathic effect (CPE) induced by coxsackievirus (CV)B1-5, CVA6, poliovirus type 1, and enterovirus 71. The aqueous extract of Syzygium brazzavillense, but not those of other plants, inhibited the CPE induced by CVB3 and CVB4 at 30 µg/mL (CC50 ; 2800 µg/mL, IC50 ; 0.8 µg/mL) and by CVB2 and poliovirus type 1 at higher concentrations. When aqueous extract of this plant was mixed with CVB4, the replication of the virus was inhibited. In conclusion, aqueous extracts of Syzygium brazzavillense can inhibit the infection with CVB4 and other enteroviruses in vitro. The present ethnopharmacological investigation helped to identify a plant with potential properties useful to combat enterovirus infections.

Neoboutonia melleri var velutina Prain: in vitro and in vivo hepatoprotective effects of the aqueous stem bark extract on acute hepatitis models.

BACKGROUND: Hepatitis is a liver inflammation caused by different agents and remains a public health problem worldwide. Medicinal plants are an important source of new molecules being considered for treatment of this disease. Our work aims at evaluating the hepatoprotective properties of Neoboutonia velutina, a Cameroonian medicinal plant. METHODS: The aqueous extract has been prepared using phytochemical methods. HepG2 cells were used to assess anti-inflammatory properties of the extract at different concentrations. Acute hepatitis models (Carbon tetrachloride and Concanavalin A) were performed in mice receiving or not receiving, different extract doses by gavage. Liver injury was assessed using histology, transaminases and pro-inflammatory markers. Extract antioxidant and radical scavenging capacities were evaluated. RESULTS: The extract led to a significant decrease in pro-inflammatory cytokine expression in vitro and to a remarkable protection of mice from carbon tetrachloride-induced liver injury, as shown by a significant decrease in dose-dependent transaminases level. Upon extract treatment, inflammatory markers were significantly decreased and liver injuries were limited as well. In the Concanavalin A model, the extract displayed weak effects. CONCLUSIONS: Taking into account underlying mechanisms in both hepatitis models, we demonstrate the extract's radical scavenging capacity. Neoboutonia velutina displays a potent hepatoprotective effect mediated through radical scavenging properties.

Antiproliferative and Antibacterial Activities of Cirsium scabrum from Tunisia.

Several Cirsium species are known for their uses in traditional medicine and consequently are studied for their phytochemical content and their biological activities. In the framework of a previous study conducted on eight extremophile plants from Tunisia, we highlighted that the crude methanolic extract of C. scabrum, a not investigated thistle, showed moderate but quite selective cytotoxic activity against the cancerous cell line J774 compared to the noncancerous cell line WI38 (IC50 = 11.53 µg/ml on J774, IC50 = 29.89 µg/ml on WI38, and selectivity index = 2.6). In the current study, the partitions of the leaves of C. scabrum were analyzed for their antiproliferative activity on the same cell lines. From the most active petroleum ether partition, we isolated four triterpenoids including lupeol, taraxasterol acetate, and a (1 : 1) mixture of 25-hydroperoxycycloart-23-en-3ß-ol and 24-hydroperoxycycloart-25-en-3ß-ol. These two cycloartane-type triterpenoids are mostly responsible for this cytotoxic activity. On the other hand, the antimicrobial potential of this plant was also evaluated against 36 microorganisms. The moderate antibacterial activity against 6 Staphylococcus aureus and 2 Dermabacter hominis strains is mainly attributed to the butanol partition whose major compounds are glycosides of flavones.

An ecological approach to discover new bioactive extracts and products: the case of extremophile plants.

OBJECTIVES: Eight extremophile plants from Tunisia were screened to find natural products with benefits in human health. METHODS: These plants were collected in different areas in Tunisia. Their methanolic extracts were evaluated for their total phenolic content and for their antiradical (DPPH), antimicrobial (on 35 bacteria and one yeast), antiviral (hepatitis C virus, HCV) and cytotoxic activity (against WI38 and J774 cell lines). The most active species were subjected to a bioguided fractionation. KEY FINDINGS: The screening revealed promising activity for four plants, but two species have both antiradical and antimicrobial activity: Juncus maritimus and Limonium virgatum. The rhizomes extract of J. maritimus showed the highest activity against HCV, a selective antibacterial activity against Streptococcus dysgalactiae, and a moderate antiradical activity which is due to luteolin isolated in one step by centrifugal partition chromatography. The stems' and leaves' extracts of L. virgatum were rich in polyphenols responsible for the antiradical activity. Also, Limonium extracts showed an antibacterial activity with a broad spectrum. CONCLUSIONS: Extremophile plants have proven to be a promising source for bioactive metabolites. They have a powerful antioxidant system highly influenced by biotic and abiotic factors and the ability to produce secondary metabolites with antimicrobial activity.

In vitro Antimicrobial Activity of Traditional Plant Used in Mestizo Shamanism from the Peruvian Amazon in Case of Infectious Diseases.

CONTEXT: Our survey was performed near Iquitos (Peruvian Amazon) and its surroundings and leads us to consider Mestizo ethnomedical practices. The plant species reported here are traditionally used for ailments related to microbial infections. Inhabitants of various ethnic origins were interviewed, and 52 selected plants extracts were evaluated for their antimicrobial properties against a panel of 36 sensitive and multi-resistant bacteria or yeast. The study aimed at providing information on antimicrobial plant extract activities and the ethnomedical context of Mestizo riverine populations from Loreto (Peru). MATERIAL AND METHOD: The minimum inhibitory concentrations (MICs) of the plant crude extracts were carried out using the agar dilution method and ranged between 0.075 and 5.0 mg/ml. RESULTS: Of the 40 plants analyzed, 9 species showed MIC ≤0.3 mg/ml (Anacardium occidentale, Couroupita guianensis, Croton lechleri, Davilla rugosa, Erythrina amazonica, Jacaranda copaia subsp. Spectabilis, Oenocarpus bataua, Peperomia macrostachya, and Phyllanthus urinaria) for one or several of the 36 microorganisms and only 6 drug extracts were inactive. Among the 40 plants, 13 were evaluated for the first time for an antibacterial activity. CONCLUSION: This evaluation of the antimicrobial activity of 40 plants using an approved standard methodology allowed comparing those activities against various microbes to establish antimicrobial spectra of standardized plant extracts, and give support to the traditional use of these plants. It may also help discovering new chemical classes of antimicrobial agents that could serve against multi-resistant bacteria. SUMMARY: This study leads us to consider Mestizo ethnomedical practices near Iquitos (Peruvian Amazon) and its surroundings. The plant species reported here are traditionally used for ailments related to microbial infections. 52 selected plants extracts were evaluated for their antimicrobial properties against a panel of 36 sensitive and multi resistant bacteria or yeast. The study aimed at providing information on antimicrobial plant extract activities and the ethnomedical context of Mestizo riverine populations from Loreto.

Rosmarinic Acid and Its Methyl Ester as Antimicrobial Components of the Hydromethanolic Extract of Hyptis atrorubens Poit. (Lamiaceae).

Primary biological examination of four extracts of the leaves and stems of Hyptis atrorubens Poit. (Lamiaceae), a plant species used as an antimicrobial agent in Guadeloupe, allowed us to select the hydromethanolic extract of the stems for further studies. It was tested against 46 microorganisms in vitro. It was active against 29 microorganisms. The best antibacterial activity was found against bacteria, mostly Gram-positive ones. Bioautography enabled the isolation and identification of four antibacterial compounds from this plant: rosmarinic acid, methyl rosmarinate, isoquercetin, and hyperoside. The MIC and MBC values of these compounds and their combinations were determined against eight pathogenic bacteria. The best inhibitory and bactericidal activity was found for methyl rosmarinate (0.3 mg/mL). Nevertheless, the bactericidal power of rosmarinic acid was much faster in the time kill study. Synergistic effects were found when combining the active compounds. Finally, the inhibitory effects of the compounds were evaluated on the bacterial growth phases at two different temperatures. Our study demonstrated for the first time antimicrobial activity of Hyptis atrorubens with identification of the active compounds. It supports its traditional use in French West Indies. Although its active compounds need to be further evaluated in vivo, this work emphasizes plants as potent sources of new antimicrobial agents when resistance to antibiotics increases dramatically.

Antifungal activity of 10 Guadeloupean plants.

Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations.

Plants used by native Amazonian groups from the Nanay River (Peru) for the treatment of malaria.

AIM OF THE STUDY: In order to evaluate the antimalarial potential of traditional remedies used in Peru, Indigenous and Mestizo populations from the river Nanay in Loreto were interviewed about traditional medication for the treatment of malaria. MATERIALS AND METHODS: The survey took place on six villages and led to the collection of 59 plants. 35 hydro-alcoholic extractions were performed on the 21 most cited plants. The extracts were then tested for antiplasmodial activity in vitro on Plasmodium falciparum chloroquine resistant strain (FCR-3), and ferriprotoporphyrin inhibition test was also performed in order to assume pharmacological properties. RESULTS: Extracts from 9 plants on twenty-one tested (Abuta rufescens, Ayapana lanceolata, Capsiandra angustifolia, Citrus limon, Citrus paradise, Minquartia guianensis, Potalia resinífera, Scoparia dulcis, and Physalis angulata) displayed an interesting antiplasmodial activity (IC(50)<10 µg/ml) and 16 remedies were active on the ferriprotoporphyrin inhibition test. CONCLUSIONS: The results give scientific validation to the traditional medical knowledge of the Amerindian and Mestizo populations from Loreto and exhibit a source of potentially active plants.

Antifungal and cytotoxic activity of withanolides from Acnistus arborescens.

Three compounds were isolated from Acnistus arborescens, a tree commonly used in South and Central America in traditional medicine against several infectious diseases, some of which are caused by fungi. Bioassay-guided fractionation of a MeOH extract of leaves, based on its anti-Pneumocystis carinii activity, led to the isolation of compounds 1-3. Mono- and bidimensional NMR analyses enabled identification of two new withanolides, (20R,22R)-5beta,6beta-epoxy-4beta,12beta,20-trihydroxy-1-oxowith-2-en-24-enolide (1) and (20R,22R)-16beta-acetoxy-3beta,4beta;5beta,6beta-diepoxy-12beta,20-dihydroxy-1-oxowith-24-enolide (2), and withanolide D (3). Antifungal activity on 13 fungi responsible for human infections (five dermatophytes, one nondermatophyte mold, six yeasts, and Pneumocystis carinii) was examined. Cytotoxicity of these compounds was also evaluated in vitro.

Humulane and germacrane sesquiterpenes from Ferula lycia.

Five new juniferol esters (1-5), along with six known humulane derivatives (6-11), were isolated from the roots of Ferula lycia, an endemic Turkish species. The fruits of the same species were also investigated and led to the isolation of these same compounds, as well as two known germacrane esters (12 and 13). All isolated sesquiterpenes were assayed for cytotoxicity against two tyrosine kinase inhibitor-resistant cell lines, K562R and DA1-3b/M2(BCR-ABL). The two most active compounds, juniferinin (7) and 6-beta-p-hydroxybenzoyloxygermacra-1(10),4-diene (12), were moderately active against Raji lymphoma cells but also displayed some toxicity against healthy bone marrow cells.

Activity of ladanein on leukemia cell lines and its occurrence in Marrubium vulgare.

Three methoxylated flavones isolated from Marrubium peregrinum - ladanein, scutellarein-5,7,4'-trimethyl ether, and scutellarein-5,6,7,4'-tetramethyl ether - were assayed for their cytotoxicity towards a recently developed dasatinib-resistant murine leukemia cell line (DA1-3b/M2 (BCR-ABL)), together with the structurally related non-methylated flavone scutellarein. The most active compound, ladanein, was looked for in 20 common Lamiaceae species by a quick HPLC screening. Among the possible positive results, the most interesting source was found to be Marrubium vulgare, which led to the isolation and identification of ladanein for the first time in this species. Ladanein also displayed moderate (20-40 microM) activities against K562, K562R (imatinib-resistant), and 697 human leukemia cell lines but was toxic neither to MOLM13 nor to human peripheral blood mononuclear cells. This work provides a common natural source for the hemi-synthesis of future ladanein-derived flavones and the study of their antileukemic activity.

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.

Letter: characterisation and identification of spermine and spermidine derivatives in Microdesmis keayana and Microdesmis puberula roots by electrospray ionisation tandem mass spectrometry and high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry.

Three new N(1),N(5),N(14)-tris(4- hydroxycinnamoyl)spermines were identified in hydromethanolic root extracts of Microdesmis keayana J. Léonard and Microdesmis puberula Hook f. The electrospray ionisation tandem mass spectrometry (ESI-MS/MS) technique with specific nuclear magnetic resonance analysis of hydrolysed products made it possible to identify N(1),N(5),N(14)-tris(p-coumaroyl)spermine, N(1)-feruloyl,N(5),N(14)-di(p-coumaroyl)spermine and N(1),N(5),N(14)-tris(feruloyl)spermine, named keayanines B, C and D, respectively. ESI-MS/MS analysis most effectively provided structural data although high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry was also used to characterise four other compounds from Microdesmis puberula-keayanidines A, B, C and keayanine A-which had already been identified in M. keayana. This chemical data is the first to be published for M. puberula which is a commonly used plant in Central African traditional medicine.