RESUMO
Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2-13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 µg/mL. The isolated metabolites dichamanetin, (E)-acetylmelodorinol, and cleistenolide showed IC50 = 9.3, 7.6 and 15.2 µM, respectively, against P. falciparum 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC50 = 42.0 µg/mL (crude extract) and 9.6-30.7 µM (isolated compounds). Our findings demonstrate the potential applicability of C. kirkii as a source of antimalarial and anticancer agents.
Assuntos
Annonaceae/química , Antimaláricos/química , Antimaláricos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/farmacologia , Annonaceae/metabolismo , Humanos , Malária/tratamento farmacológico , Conformação Molecular , Estrutura Molecular , Testes de Sensibilidade Parasitária , Análise EspectralRESUMO
A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A-D (2-5), along with nine known compounds (6-14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 µM, respectively.
Assuntos
Isoflavonas/isolamento & purificação , Millettia/química , Folhas de Planta/química , Rotenona/isolamento & purificação , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Isoflavonas/química , Isoflavonas/farmacologia , Quênia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Rotenona/química , Rotenona/farmacologiaRESUMO
Prenylated and O-methylflavonoids including one new pterocarpan (1), three new isoflavones (2-4), and nineteen known natural products (5-23) were isolated and identified from the root, stem bark, and leaf extracts of Erythrina schliebenii. The crude extracts and their constituents were evaluated for antitubercular activity against Mycobacterium tuberculosis (H37Rv strain), showing MICs of 32-64 µg mL-1 and 36.9-101.8 µM, respectively. Evaluation of their toxicity against the aggressive human breast cancer cell line MDA-MB-231 indicated EC50 values of 13.0-290.6 µM (pure compounds) and 38.3 to >100 µg mL-1 (crude extracts).
Assuntos
Antituberculosos/isolamento & purificação , Erythrina/classificação , Flavonoides/isolamento & purificação , Antituberculosos/química , Antituberculosos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Flavonoides/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Raízes de Plantas/química , TanzâniaRESUMO
Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A-F (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised based on comparison of its NMR spectroscopic features and optical rotation to those of 1, for which the configuration was determined by X-ray diffraction. Observation of the co-occurrence of cyclohexenoids and heptenolides in C. kirkii is of biogenetic and chemotaxonomic significance. Some of the isolated compounds showed activity against Plasmodium falciparum (3D7, Dd2), with IC50 values of 0.2-40 µM, and against HEK293 mammalian cells (IC50 2.7-3.6 µM). While the crude extract was inactive at 100 µg/mL against the MDA-MB-231 triple-negative breast cancer cell line, some of its isolated constituents demonstrated cytotoxic activity with IC50 values ranging from 0.03-8.2 µM. Compound 1 showed the most potent antiplasmodial (IC50 0.2 µM) and cytotoxic (IC50 0.03 µM, MDA-MB-231 cell line) activities. None of the compounds investigated exhibited translational inhibitory activity in vitro at 20 µM.
Assuntos
Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/química , Neoplasias da Mama/tratamento farmacológico , Cicloexenos/isolamento & purificação , Cicloexenos/farmacologia , Células HEK293/patologia , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antineoplásicos Fitogênicos/química , Cicloexenos/química , Células HEK293/química , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Difração de Raios XRESUMO
The phytochemical investigation of the CH2Cl2/MeOH (1:1) extract of the roots of Pentas parvifolia led to the isolation of three new naphthalenes, parvinaphthols A (1), B (2), and C (3), two known anthraquinones, and five known naphthalene derivatives. Similar investigation of the roots of Pentas bussei afforded a new polycyclic naphthalene, busseihydroquinone E (4), a new 2,2'-binaphthralenyl-1,1'-dione, busseihydroquinone F (5), and five known naphthalenes. All purified metabolites were characterized by NMR and MS data analyses, whereas the absolute configurations of 3 and 4 were determined by single-crystal X-ray diffraction studies. The E-geometry of compound 5 was supported by DFT-based chemical shift calculations. Compounds 2-4 showed marginal cytotoxicity against the MDA-MB-231 human triple-negative breast cancer cell line with IC50 values ranging from 62.3 to 129.6 µM.
Assuntos
Antraquinonas/isolamento & purificação , Naftalenos/isolamento & purificação , Rubiaceae/química , Antraquinonas/química , Antraquinonas/farmacologia , Antimaláricos/química , Cristalografia por Raios X , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Naftalenos/química , Naftalenos/farmacologia , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Plasmodium falciparum/efeitos dos fármacosRESUMO
Seven N-cinnamoyltetraketides (1-7), including the new Z-toussaintine E (2), toussaintine F (6), and toussaintine G (7), were isolated from the methanol extract of the leaves of Toussaintia orientalis using column chromatography and HPLC. The configurations of E-toussaintine E (1) and toussaintines A (3) and D (5) are revised based on single-crystal X-ray diffraction data from racemic crystals. Both the crude methanol extract and the isolated constituents exhibit antimycobacterial activities (MIC 83.3-107.7 µM) against the H37Rv strain of Mycobacterium tuberculosis. Compounds 1, 3, 4, and 5 are cytotoxic (ED50 15.3-105.7 µM) against the MDA-MB-231 triple negative aggressive breast cancer cell line.
Assuntos
Annonaceae/química , Antituberculosos/isolamento & purificação , Cinamatos/isolamento & purificação , Cicloexanonas/isolamento & purificação , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/química , Antituberculosos/farmacologia , Cinamatos/química , Cinamatos/farmacologia , Cicloexanonas/química , Cicloexanonas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , TanzâniaRESUMO
Five new compounds, 4-O-geranylisoliquiritigenin (1), 12-dihydrousararotenoid B (2), 12-dihydrousararotenoid C (3), 4'-O-geranyl-7-hydroxyflavanone (4), and 4'-O-geranyl-7-hydroxydihydroflavanol (5), along with 12 known natural products (6-17) were isolated from the CH2Cl2/MeOH (1:1) extract of the root bark of Millettia usaramensis ssp. usaramensis by chromatographic separation. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas their absolute configurations were established on the basis of chiroptical data and in some cases also by X-ray crystallography. The crude extract was moderately active (IC50 = 11.63 µg/mL) against the ER-negative MDB-MB-231 human breast cancer cell line, and accordingly compounds 6, 8, 9, 10, 12, and 16 also showed moderate to low cytotoxic activities (IC50 25.7-207.2 µM). The new natural product 1 exhibited antiplasmodial activity with IC50 values of 3.7 and 5.3 µM against the chloroquine-sensitive 3D7 and the chloroquine-resistant Dd2 Plasmodium falciparum strains, respectively, and was also cytotoxic to the HEK293 cell line.
Assuntos
Antimaláricos/isolamento & purificação , Chalconas/isolamento & purificação , Flavonoides/isolamento & purificação , Millettia/química , Antimaláricos/química , Antimaláricos/farmacologia , Chalconas/química , Chalconas/farmacologia , Cloroquina/farmacologia , Cristalografia por Raios X , Flavanonas , Flavonoides/química , Flavonoides/farmacologia , Células HEK293 , Humanos , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Extratos Vegetais/química , Plasmodium falciparum/efeitos dos fármacosRESUMO
A new triterpenoid, 3-oxo-12ß-hydroxy-oleanan-28,13ß-olide (1), and six known triterpenoids 2-7 were isolated from the root bark of Ekebergia capensis, an African medicinal plant. A limonoid 8 and two glycoflavonoids 9-10 were found in its leaves. The metabolites were identified by NMR and MS analyses, and their cytotoxicity was evaluated against the mammalian African monkey kidney (vero), mouse breast cancer (4T1), human larynx carcinoma (HEp2) and human breast cancer (MDA-MB-231) cell lines. Out of the isolates, oleanonic acid (2) showed the highest cytotoxicity, i.e., IC50's of 1.4 and 13.3 µM against the HEp2 and 4T1 cells, respectively. Motivated by the higher cytotoxicity of the crude bark extract as compared to the isolates, the interactions of oleanonic acid (2) with five triterpenoids 3-7 were evaluated on vero cells. In an antiplasmodial assay, seven of the metabolites were observed to possess moderate activity against the D6 and W2 strains of P. falciparum (IC50 27.1-97.1 µM), however with a low selectivity index (IC50(vero)/IC50(P. falciparum-D6)<10). The observed moderate antiplasmodial activity may be due to general cytotoxicity of the isolated triterpenoids.
Assuntos
Antimaláricos/farmacologia , Meliaceae/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Raízes de Plantas/química , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/isolamento & purificação , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Camundongos , Testes de Sensibilidade Parasitária , Extratos Vegetais/isolamento & purificação , Células VeroRESUMO
As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae), a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the new naphthoquinone 8,8'-oxo-biplumbagin (1) was isolated along with the known tetralones trans-isoshinanolone (2) and cis-isoshinanolone (3), and the naphthoquinones plumbagin (4) and 3,3'-biplumbagin (5). Compounds 2, 4, and 5 showed cytotoxicity (IC50 520-82.1 µM) against MDA-MB-231 breast cancer cells. Moderate to low cytotoxicity was observed for the hexane, dichloromethane, and methanol extracts of the root bark (IC50 16.1, 29.7 and > 100 µg/mL, respectively), and for the methanol extract of the stem bark (IC50 59.6 µg/mL). The radical scavenging activity of the isolated constituents (1-5) was evaluated on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The applicability of the crude extracts and of the isolated constituents for controlling degenerative diseases is discussed.
RESUMO
Selenium deficiency in humans has been associated with various diseases, the risks of which can be reduced through dietary supplementation. Selenium accumulating plants may provide a beneficial nutrient for avoiding such illnesses. Thus, leafy vegetables such as Amaranthus hybridus, Amaranthus sp., Cucurbita maxima, Ipomoea batatas, Solanum villosum, Solanum scabrum, and Vigna unguiculata were explored for their capabilities to accumulate selenium when grown on selenium enriched soil and for use as a potential source of selenium enriched functional foods. Their selenium contents were determined by spectrophotometry using the complex of 3,3'-diaminobenzidine hydrochloride (DABH) as a chromogen. The mean concentrations in the leaves were found to range from 7.90 ± 0.40 to 1.95 ± 0.12 µg/g dry weight (DW), with C. maxima accumulating the most selenium. In stems, the accumulated selenium content ranged from 1.12 ± 0.10 µg/g in Amaranthus sp. to 5.35 ± 0.78 µg/g DW in C. maxima and was hence significantly different (P < 0.01). The cancer cell line MDA-MB-231 was used in cytotoxicity assays to determine the anticancer potential of these extracts. With exception of S. scabrum and S. villosum, no cytotoxicity was detected for the selenium enriched vegetable extracts up to 100 µg/mL concentration. Hence, following careful evaluation the studied vegetables may be considered as selenium enriched functional foods.