[show abstract][hide abstract] ABSTRACT: Two new pentacyclic triterpenoids, xyloketal (1), a 3,25-epoxy-olean-12-ene, and 3b,21a-dihydrox-yglut-5-ene (2) along with seven known triterpene compounds (3–9) were isolated from the root barks of Cassine xylocarpa and Celastrus vulcanicola. Their structures were characterized by spectroscopic methods, mainly NMR (1H, 13C, HSQC, HMBC and ROESY) and EIMS, and comparison with data reported in the literature. Also molecular mechanic calculations were used to calculate the minimum energy conformer of compound 1 and its epimer.
[show abstract][hide abstract] ABSTRACT: Type 2 diabetes mellitus (T2DM) is a rapidly expanding public epidemic and frequently results in severe vascular complications. In an attempt to find anti-diabetic agents, we report herein on the isolation, structural elucidation and bioactivity of nine friedelane-type triterpenes (1-9) and twenty two known ones (10-31) from the root barks of Celastrus vulcanicola and Maytenus jelskii. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Two compounds from this series (1 and 3) exhibited increased insulin-mediated signalling, which suggests these friedelane triterpenes have potential therapeutic use in insulin resistant states.
[show abstract][hide abstract] ABSTRACT: Six new withanolides (1-6) along with eleven known ones (7-17) were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Semisynthesis of the minority metabolites 7 and 15 from compounds 6 and 9, respectively, as starting material, was performed. The isolated compounds as well as three derivatives (7a, 9a and 9b) of withaferin A were evaluated for cytotoxicity against HeLa (carcinoma of the cervix), A-549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines, and against normal Vero cells (African green monkey kidney). Five compounds from this series (8, 9a, 9b, 11 and 13) exhibited potent antiproliferative effects on the tumor cells, even higher than the well known anticancer agent, withaferin A (9). Phosphatidylserine externalization, chromatin condensation, and caspase-3 activation clearly indicated apoptosis as a mechanism of action. The structure-activity relationship revealed valuable information on the pharmacophore for withanolide-type compounds.
European journal of medicinal chemistry 06/2012; 54:499-511. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the present study we report the isolation of nine new olean-18-ene triterpenes (1-9), along with three known ones (10-12), from Cassine xylocarpa and Maytenus jelskii. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques (COSY, ROESY, HSQC and HMBC), and spectrometric methods. The natural compounds and derivatives 13-15 have been tested for their potential as inhibitors of human immunodeficiency virus type 1 replication. Five compounds from this series displayed potent antiviral activity with IC(50)s in the micromolar range (1, 3, 4, 7 and 8) being 1 and 8 the most active compounds. The target of these compounds was different from antiretroviral drugs currently licensed as they act as inhibitors of enhancer-dependent transcription. The structure-activity relationships were established based on the regiosubstitution and oxidation degree of the triterpene scaffold, revealing that these aspects were able to modulate the selectivity and intensity of HIV inhibition.
European journal of medicinal chemistry 03/2012; 52:295-303. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: The phytochemical analysis of the root bark extracts of the Chilean Maytenus, M. chubutensis, and M. magellanica (Celastraceae), led to the isolation of one phenolic nortriterpene, 1, and one diterpene with a nor-ent-kaurene skeleton, 2. In addition, four known compounds were isolated, among which compound 3 has been isolated for the first time from a natural source. Their structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR (COSY, ROESY, HSQC, and HMBC) experiments, comparison with data reported in the literature, and chemical correlations. The isolated compounds were assayed for their reversal activity against a multidrug-resistant Leishmania tropica line, overexpressing a P-glycoprotein related transporter. Compound 1 showed moderate multidrug-resistance reversal activity.
[show abstract][hide abstract] ABSTRACT: Sixteen (1-16) dihydro-β-agarofuran sesquiterpenes were isolated from the fruits of Maytenus jelskii and evaluated against mammalian cells with a multidrug resistance phenotype mediated by the overexpression of the human P-glycoprotein. Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, CD studies, chemical correlations and biogenetic means. Eight compounds from this series were discovered as potent chemosensitizers (1, 2, 4, 6, 8, 9, 11 and 14), showing similar effectiveness to or higher than the classical P-glycoprotein reversal agent verapamil, a first-generation chemosensitizer, when reversing resistance to daunomycin and vinblastine. Detailed structure-activity relationships revealed that aromatic substituents at the 6 and 9-position of the sesquiterpene scaffold were able to modulate the intensity of inhibition.
European journal of medicinal chemistry 08/2011; 46(10):4915-23. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Uragogin and blepharodin were isolated from Crossopetalum uragoga and Maytenus magellanica, respectively.
They represent the first examples of a triterpeneeneolignan ester and a heptacyclic arylpropanoid-nor-triterpenephenol, hetero-DielseAlder adducts built with dioxane bridges. Their proposed biosynthetic route is discussed.
[show abstract][hide abstract] ABSTRACT: In the present study, we report four new dihydro-β-agarofuran sesquiterpenes (1-4), which were isolated from the leaves of Celastrus vulcanicola, in addition to five derivatives (5-9). Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, X-ray studies, chemical correlations and biogenetic means. Compounds 1-9 and the previously reported sesquiterpenes 10-25 have been tested as potential antimycobacterial agents against sensitive and resistant Mycobacterium tuberculosis strains. 1α-Acetoxy-6β,9β-dibenzoyloxy-dihydro-β-agarofuran (20) exhibited antituberculosis activity against the MDR TB strain with a MIC value of 6.2 μg/mL, comparable to or better than isoniazid or rifampin, two of the best first-line drugs commonly used in the treatment of TB. The structure-activity relationship is discussed.
[show abstract][hide abstract] ABSTRACT: Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model.
[show abstract][hide abstract] ABSTRACT: A new bicyclic diterpene with a labdane skeleton, 7-oxo-labd-8-en-15-ol ( 1), along with two known diterpenes and ten flavonoids were isolated from the leaves of Aeonium lindleyi (Crassulaceae). Their structures were elucidated on the basis of spectroscopic data, including 1D and 2D NMR experiments, and comparison with spectroscopic data reported in the literature. Labdan-8 α,15-diol (2) and labd-8(17)-en-3 β,15-diol (3) showed leishmanicidal activity against Leishmania tropica (IC (50) = 77.0 µM) and Leishmania braziliensis (IC (50) = 68.0 µM) similar to ketoconazole used as positive control. 5,3'-Dihydroxy-3,7,4',5'-tetramethoxyflavone (8) and combretol (9) showed moderate activity (growth inhibition 87.3 and 73.0 %, respectively, at 50 µM) against a multidrug-resistant L. tropica line.
[show abstract][hide abstract] ABSTRACT: Seven new withanolides (1-7), along with three known ones (8-10), were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 2D NMR experiments and spectrometric techniques, and the absolute configuration of 1 and 2 was established by CD analysis. In the search for new cytotoxic compounds from Withania species, the isolated compounds 1-9, along with two derivatives, were assayed for their cytotoxicity against HeLa, MCF-7 and A-549 human tumor cell lines. Derivative (4S,20R,22R)-27-acetoxy-4-p-bromobenzoyloxy-1-oxo-witha-2,5,16,24-tetraenolide (13) showed cytotoxicity against all the cell lines assayed with IC(50) values ranging from 2.8 to 3.6microM, and (4S,20R,22R)-4,27-diacetoxy-4-hydroxy-1-oxo-witha-2,5,16,24-tetraenolide (12) exhibited an IC(50) value of 5.4microM on the MCF-7 cell line.
[show abstract][hide abstract] ABSTRACT: Five friedelane triterpenoids, epifriedelinol (1), friedelin (2), canophyllol (3), pulpononic acid (4) and 3-oxo-29-hydroxyfriedelane (5), were isolated from Celastrus vulcanicola (Celastraceae), and were identified by spectroscopic methods, comparison with authentic samples and reported data. In the search for potential herbicides, compounds 1-5 were evaluated for their photosynthetic inhibitory activity. Compound 1 acts as an energy transfer inhibitor, interacting and enhancing the light-activated Mg(2+)-ATPase, while 3 behaves as a Hill reaction inhibitor. The in vivo assays indicated that 1 and 3 act as selective postemergence herbicides at 100 μM by reducing biomass production in the weed Physalis ixocarpa. Moreover, results from Chl a fluorescence transients in leaves of Lolium perenne and P. ixocarpa suggest that both compounds affect photosynthesis efficiency of the chloroplasts as a response to a process of detoxification and repair. Thus, 1 and 3 reduce biomass by more complex mechanisms than only the damaging of the photosynthetic apparatus.
Journal of Agricultural and Food Chemistry 09/2010; · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: A series of apocarotenoids (1-8) and one carotenoid (9) were isolated from the leaves of Withania aristata. In addition, the tetraacetylated apocarotenoid glucosides 10-12 were obtained by acetylation, with derivative 9-hydroxymegastigma-4,6E-dien-3-one 9-O-beta-D-glucopyranoside tetraacetate (10) being described for the first time. The structures have been determined by spectroscopic and spectrometric means, mainly NMR and ESI-MS, and comparison with data reported in the literature. These metabolites were evaluated on a systematic phytotoxicity assay using the etiolated wheat coleoptile bioassay. Compounds 1-3, 9 and 12 were further assayed for their phytotoxicity on the target species Lepidium sativum, Lactuca sativa, Lycopersicum esculentum and Allium cepa. Among the assayed compounds, lutein (9) showed the most significant values for phytotoxicity, followed by the non-glycosylated apocarotenoids (6S, 9R)-vomifoliol (1) and 9-hydroxymegastigma-4,6E-dien-3-one (2).
[show abstract][hide abstract] ABSTRACT: Seven new (1-4 and 7-9) sesquiterpenes with a dihydro-beta-agarofuran skeleton, along with four known compounds (5, 6, 10, and 11), have been isolated from the leaves of Maytenus jelskii. The structures of the new compounds were elucidated by means of spectroscopic data analysis, including 1D and 2D NMR techniques, and their absolute configurations were determined by circular dichroism and chemical correlations. The compounds have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Compound 10 was found to be an effective antitumor-promoting agent and also showed a potent chemopreventive effect in an in vivo two-stage carcinogenesis model.
Journal of Natural Products 02/2010; 73(2):127-32. · 3.29 Impact Factor