RESUMEN
In an effort to find potent natural inhibitors of RhoA and p115 signaling G-proteins, a systematic in vitro evaluation using enzymatic and plasmonic resonance assays was undertaken on 11â¯317 plant extracts. The screening procedure led to the selection of the New Caledonian endemic species Meiogyne baillonii for a chemical investigation. Using a bioguided isolation procedure, three enediyne-γ-butyrolactones (1-3) and two enediyne-γ-butenolides (4 and 5), named sapranthins H-L, respectively, two enediyne carboxylic acid (6 and 7), two depsidones, stictic acid (8) and baillonic acid (9), aristolactams AIa and AIIa (10 and 11), and two aporphines, dehydroroemerine (12) and noraristolodione (13), were isolated from the ethyl acetate extract of the bark. The structures of the new compounds (1-6, 9, and 11) and their relative configurations were established by NMR spectroscopic analysis and by X-ray diffraction analysis for compound 9. Only stictic acid (8) exhibited a significant inhibiting activity of the RhoA-p115 complex, with an EC50 value of 0.19 ± 0.05 mM. This is the first time that a natural inhibitor of the complex RhoA-p115's activity was discovered from an HTS performed over a collection of higher plant extracts. Thus, stictic acid (8) could be used as the first reference compound inhibiting the interaction between RhoA and p115.
Asunto(s)
Annonaceae/química , Extractos Vegetales/farmacología , Factores de Intercambio de Guanina Nucleótido Rho/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Espectroscopía de Resonancia Magnética , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/químicaRESUMEN
In our continuing phytochemical screening program aimed at finding major constituents. of endemic Madagascar plants as potential templates for semisynthesis, we investigated the ethyl acetate extract of stem bark of Garcinia verrucosa. Fractionation of the extract led to the isolation of the major compound named garcicosin. -Its structure was elucidated by spectroscopic methods including ID and 2D homo- and heteronuclear NMR techniques (COSY, HSQC, HMBC and NOESY), and HR-mass spectromnetry.
Asunto(s)
Garcinia/química , Floroglucinol/análogos & derivados , Floroglucinol/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Modelos Moleculares , Estructura MolecularRESUMEN
Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11 Mediterranean Euphorbia and one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant and selective antiviral activity in a Chikungunya virus-cell-based assay. An LC-MS(2) dereplication method was then developed to investigate whether known diterpenoids with anti-CHIKV activity, such as the potent anti-CHIKV 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-didecanoate, and prostratin as well as 24 other commercially available diterpenoids of tigliane-, ingenane-, and daphnane-type for which the anti-CHIKV activity have been established in advance (Nothias-Scaglia et al. 2015), were present in the Euphorbia extracts. Only ingenol-3-mebutate, 13-O-isobutyryl-12-deoxyphorbol-20-acetate, and ingenol-3,20-dibenzoate, all exhibiting weak anti-CHIKV activities, were detected in the EtOAc extracts of Euphorbia peplus, Euphorbia segetalis ssp. pinea, and Euphorbia pithyusa ssp. pithyusa. Given the potent anti-CHIKV activities of these Euphorbia extracts, the present study suggested that their antiviral activities are probably due to untargeted diterpenoids.
Asunto(s)
Antivirales/química , Virus Chikungunya/efectos de los fármacos , Euphorbia/química , Extractos Vegetales/química , Replicación Viral/efectos de los fármacos , Animales , Antivirales/aislamiento & purificación , Virus Chikungunya/fisiología , Chlorocebus aethiops , Diterpenos/química , Diterpenos/aislamiento & purificación , Estructura Molecular , Células VeroRESUMEN
A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanosoma brucei gambiense, in addition to tubulin polymerization inhibition at low micromolar concentration. We also provide a full set of NMR data as some of the flavones were incompletely described.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antiparasitarios/farmacología , Flavonoides/farmacología , Gardenia/química , Extractos Vegetales/química , Inhibidores de la Angiogénesis/síntesis química , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Animales , Antiparasitarios/síntesis química , Antiparasitarios/química , Antiparasitarios/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Flavonoides/síntesis química , Flavonoides/química , Flavonoides/aislamiento & purificación , Flores/química , Humanos , Leishmania/efectos de los fármacos , Estructura Molecular , Nueva Caledonia , Plasmodium falciparum/efectos de los fármacos , Relación Estructura-Actividad , Trypanosoma brucei gambiense/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The plant Neoboutonia macrocalyx has been reported in traditional medicine to be used in the treatment of malaria. AIM OF THE STUDY: To study the in vitro antiplasmodial activity of compounds from the stem bark of Neoboutonia macrocalyx. MATERIALS AND METHODS: Compounds were extracted and purified from stem bark of Neoboutonia macrocalyx and their structure identified and confirmed by spectroscopic methods. The crude ethyl acetate extract, aqueous extract and the isolated compounds were evaluated for antiplasmodial activity against the chloroquine sensitive Sierra Leone I (D6) and chloroquine-resistant Indochina I (W2) strains of Plasmodium falciparum. RESULTS: Chemical investigation of the ethyl acetate extract of Neoboutonia macrocalyx bark resulted in the identification of one new diterpenoid; neoboutomacroin (1) in addition to the four known compounds which included, a phenanthrene; 3,6-dihyroxy-1,7-dimethyl-9-methoxyphenanthrene (2), a sterol; 3-O-Acetyloleuritolic acid (3) and two diterpenoids; simplexin (4) and montanin (5). Compounds 1 and 5 displayed good antiplasmodial activity of IC50 values less than 10 µg/mL against both strains. However, all the compounds tested displayed high cytotoxic activity against MRC5 cell line with IC50 less than 10 µM. CONCLUSIONS: Despite an indirect in vitro antiplasmodial activity of some compounds isolated from the stem bark of Neoboutonia macrocalyx, the identification of these bioactive compounds indicates that they may play a role in the pharmacological properties of this plant.
Asunto(s)
Antimaláricos/farmacología , Euphorbiaceae/química , Corteza de la Planta/química , Tallos de la Planta/química , Plasmodium falciparum/efectos de los fármacos , Antimaláricos/químicaRESUMEN
A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A-G (1-7), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15-17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1.
Asunto(s)
Ácidos Carboxílicos/química , Lauraceae/química , Estructura Molecular , Extractos Vegetales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Extractos Vegetales/farmacología , Difracción de Rayos XRESUMEN
Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine.
Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Gymnema sylvestre/química , Hifa/efectos de los fármacos , Saponinas/farmacología , Esporas Fúngicas/efectos de los fármacos , Triterpenos/farmacología , Animales , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/microbiología , Candida albicans/crecimiento & desarrollo , Candida albicans/patogenicidad , Humanos , Hifa/crecimiento & desarrollo , Hifa/patogenicidad , Extractos Vegetales/química , Saponinas/química , Saponinas/aislamiento & purificación , Esporas Fúngicas/crecimiento & desarrollo , Esporas Fúngicas/patogenicidad , Triterpenos/química , Triterpenos/aislamiento & purificación , Virulencia/efectos de los fármacosRESUMEN
In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S. decipiens, S. guianensis and S. poeppigii. Among these compounds, velutinam, aristolactam AIIIA and medioresinol showed submicromolar IC50 values on DYRK1A.
Asunto(s)
Aporfinas/farmacología , Proteína Quinasa CDC2/antagonistas & inhibidores , Ciclina B/antagonistas & inhibidores , Alcaloides Indólicos/farmacología , Lactamas/farmacología , Extractos Vegetales/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Aporfinas/química , Alcaloides Indólicos/química , Lactamas/química , Resonancia Magnética Nuclear Biomolecular , Extractos Vegetales/química , Quinasas DyrKRESUMEN
Leaf material from nine Ni hyperaccumulating species was collected in New Caledonia: Homalium kanaliense (Vieill.) Briq., Casearia silvana Schltr, Geissois hirsuta Brongn. & Gris, Hybanthus austrocaledonicus Seem, Psychotria douarrei (G. Beauvis.) Däniker, Pycnandra acuminata (Pierre ex Baill.) Swenson & Munzinger (syn Sebertia acuminata Pierre ex Baill.), Geissois pruinosa Brongn. & Gris, Homalium deplanchei (Viell) Warb. and Geissois bradfordii (H.C. Hopkins). The elemental concentration was determined by inductively-coupled plasma optical emission spectrometry (ICP-OES) and from these results it was found that the species contained Ni concentrations from to 250-28,000 mg/kg dry mass. Gas chromatography mass spectrometry (GC-MS)-based metabolite profiling was then used to analyse leaves of each species. The aim of this study was to target Ni-binding ligands through correlation analysis of the metabolite levels and leaf Ni concentration. Approximately 258 compounds were detected in each sample. As has been observed before, a correlation was found between the citric acid and Ni concentrations in the leaves for all species collected. However, the strongest Ni accumulator, P. douarrei, has been found to contain particularly high concentrations of malonic acid, suggesting an additional storage mechanism for Ni. A size exclusion chromatography separation protocol for the separation of Ni-complexes in P. acuminata sap was also applied to aqueous leaf extracts of each species. A number of metabolites were identified in complexes with Ni including Ni-malonate from P. douarrei. Furthermore, the levels for some metabolites were found to correlate with the leaf Ni concentration. These data show that Ni ions can be bound by a range of small molecules in Ni hyperaccumulation in plants.
Asunto(s)
Metaboloma , Níquel/metabolismo , Hojas de la Planta/metabolismo , Cromatografía en Gel , Ácido Cítrico/química , Análisis por Conglomerados , Cromatografía de Gases y Espectrometría de Masas , Ligandos , Magnoliopsida/metabolismo , Malonatos/química , Nueva Caledonia , Níquel/análisis , Extractos Vegetales/metabolismo , Suelo/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The study was done to establish medicinal plants used in the treatment of various diseases by the people in the Northern sector of Kibale National Park in western Uganda. It was also aimed at establishing the plant parts used and the mode of preparation of remedies. These plants create a basis for phytochemical evaluation which can lead to the discovery of biologically active compounds that can be used as starting materials in the development of new drugs targeting selected diseases such as malaria. MATERIALS AND METHODS: The required information was obtained using open interviews, semi-structured questionnaires, focus group discussions and transect walks. RESULTS: Different medicinal plants (131 species) distributed over 55 families were observed to be used by the local communities around the Northern sector of Kibale National Park. The plants as reported in this paper are used to treat 43 physical illnesses/diseases. The most used parts of the plants are the leaves. Water is the main medium used for the preparation of the remedies which are mostly administered orally. CONCLUSION: The people in the study area have a rich heritage of traditional plants that are used in the health care system to treat diseases. These medicinal plants have contributed significantly to several disease therapies. The most common diseases treated are malaria and cough, which are mostly treated by Vernonia amygdalina Del. and Albizia coriaria Welw. respectively. The main sources of medicinal plants include bush land, home gardens, grasslands, and the forest.
Asunto(s)
Medicinas Tradicionales Africanas , Fitoterapia , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Humanos , Entrevistas como Asunto , Hojas de la Planta , UgandaRESUMEN
AIM OF THE STUDY: In Uganda, malaria is the most common disease and Ugandan people largely rely on traditional medicine. In this context, we carried out an ethnobotanical study on the Kiohima village, located close to the Kibale National Park in South-Western Uganda and investigated in vitro the antiplasmodial and cytotoxic activities of selected medicinal plants. MATERIALS AND METHODS: Seventy-five plants-using adults (men and women) were interviewed to find out their plant use. From these information, 48 plants used in traditional medicine were identified and according to their reported uses and to bibliographic data, several parts of 28 plants (leaves, barks, roots), were selected and collected for biological evaluations. These samples were dried, extracted with ethyl acetate and the crude extracts were assayed for in vitro antiplasmodial and cytotoxic activities at 10 µg/mL. RESULTS: One third of the screened plants showed a significant antiplasmodial activity with inhibition greater than 50% at 10 µg/mL. CONCLUSION: These results may indicate a possible explanation of the use of some medicinal plant against malaria in the village of Kiohima and have also allowed to highlight a plant with potent antimalarial activity: Citropsis articulata root barks.
Asunto(s)
Antimaláricos/farmacología , Antineoplásicos Fitogénicos/farmacología , Plantas Medicinales , Adulto , Antimaláricos/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Etnofarmacología , Femenino , Humanos , Malaria Falciparum/tratamiento farmacológico , Masculino , Medicinas Tradicionales Africanas , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Plantas Medicinales/química , Plasmodium falciparum/efectos de los fármacos , UgandaRESUMEN
In the framework of the phytochemical investigation of plant species eaten by wild chimpanzees in their natural environment in Uganda, leaf samples of Markhamia lutea were selected and collected. The crude ethyl acetate extract of M. lutea leaves exhibited significant in vitro anti-parasitic activity and low cytotoxicity against MRC5 and KB cells. Fractionation of this extract led to six cycloartane triterpenoids, musambins A-C and their 3-O-xyloside derivatives musambiosides A-C. The structures were elucidated on the basis of spectral studies including mass spectroscopy and extensive 2D NMR. Most of the compounds exhibited mild anti-leishmanial and anti-trypanosomal activities.
Asunto(s)
Magnoliopsida/química , Pan troglodytes , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Triterpenos/farmacología , Animales , Antimaláricos/química , Antimaláricos/farmacología , Antiprotozoarios/química , Antiprotozoarios/farmacología , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Leishmania/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Plasmodium falciparum/efectos de los fármacos , Triterpenos/química , Tripanocidas/química , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Investigation of an EtOAc extract of the bark of Libocedrus chevalieri led to the isolation of a new cytotoxic lignan, 5-methoxy-4-epipodophyllotoxin (1), and three known podophyllotoxin analogues, 5-methoxypodophyllotoxin, 5-methoxypodophyllotoxin-4-O-beta-D-glucoside, and podophyllotoxin-4-O-beta-D-glucoside. Six sesquiterpenoids and a diterpenoid were also obtained. Of these, compounds 2-4 are new sesquiterpenoids, named libocedrines A-C, and 3beta-hydroxyilicic alcohol was isolated for the first time from a higher plant. Structures of the new compounds were determined on the basis of spectroscopic methods. Cytotoxicity of the isolated compounds against KB and L1210 cells and their effects on tubulin assembly were evaluated.
Asunto(s)
Antineoplásicos Fitogénicos , Cupressaceae/química , Lignanos , Plantas Medicinales/química , Podofilotoxina , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células KB , Lignanos/química , Lignanos/aislamiento & purificación , Lignanos/farmacología , Estructura Molecular , Nueva Caledonia , Corteza de la Planta/química , Podofilotoxina/análogos & derivados , Podofilotoxina/química , Podofilotoxina/aislamiento & purificación , Podofilotoxina/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacologíaRESUMEN
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.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Benzofenonas/aislamiento & purificación , Garcinia/química , Antineoplásicos Fitogénicos/química , Benzofenonas/química , Humanos , Células KB , Espectroscopía de Resonancia Magnética , Conformación Molecular , Nueva CaledoniaRESUMEN
One alpha-pyrone, obolactone (1), two chalcones, kurzichalcolactone B (2) and obochalcolactone (3), and two flavanones, oboflavanones A (4) and B (5), have been isolated from the fruits and the trunk bark of Cryptocarya obovata. The structures of the new compounds were elucidated by spectroscopic interpretations. The absolute configuration of obolactone (1) was established by circular dichroism. Obolactone (1) and obochalcolactone (3) display significant activity in in vitro cytotoxic assays against the KB cell line. Biosynthetic pathways for oboflavanones and obochalcolactone are suggested.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Flavonoides/aislamiento & purificación , Lauraceae/química , Plantas Medicinales/química , Pironas/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Dicroismo Circular , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Flavonoides/química , Flavonoides/farmacología , Humanos , Células KB , Conformación Molecular , Estructura Molecular , Corteza de la Planta/química , Pironas/química , Pironas/farmacologíaRESUMEN
Two new xanthones, 6-O-methyl-2-deprenylrheediaxanthone B (1) and vieillardixanthone (2), were isolated from the stem bark of Garcinia vieillardii, as were four known compounds (4-7). The structures of 1 and 2 were determined by means of spectroscopic analysis and chemical derivatization. Each isolate was tested for its antioxidant properties based on a scavenging activity study using the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical.
Asunto(s)
Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Garcinia/química , Plantas Medicinales/química , Xantonas/aislamiento & purificación , Antioxidantes/química , Compuestos de Bifenilo , Depuradores de Radicales Libres/química , Estructura Molecular , Nueva Caledonia , Resonancia Magnética Nuclear Biomolecular , Picratos/farmacología , Corteza de la Planta/química , Xantonas/química , Xantonas/farmacologíaRESUMEN
The alkaloids norchelerythrine, magnoflorine and (-)(S)-O-methylbalfourodinium cation were isolated from Zanthoxylum scandens bark collected in Vietnam, together with the flavanone glycoside hesperidin and the phenylpropanoids (E)-O-geranylconiferyl alcohol and (E)-O-geranylconiferyl alcohol (9Z, 12Z)-linoleate. This latter is a novel compound whose structure was elucidated on the basis of its spectral data and confirmed by chemical correlation.