RESUMO
In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 µM against the drug sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines. It is interesting to note that 3 was more active than the standard drug, doxorubicin against CEM/ADR5000 leukemia cells. Compounds 3 and 6 showed good selectivity on leukemia cells than normal cells. In future studies 3 should be tested against a panel of drug resistant human cells.
Assuntos
Carbolinas/uso terapêutico , Cinamatos/uso terapêutico , Dioxóis/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Alcaloides Indólicos/uso terapêutico , Leucemia/tratamento farmacológico , Alcamidas Poli-Insaturadas/uso terapêutico , Zanthoxylum/química , Apoptose/efeitos dos fármacos , Carbolinas/química , Carbolinas/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cinamatos/química , Cinamatos/farmacologia , Dioxóis/química , Dioxóis/farmacologia , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/química , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologiaRESUMO
BACKGROUND: Cancer constitutes a major hurdle worldwide and its treatment mainly relies on chemotherapy. OBJECTIVES: The present study was designed to evaluate the cytotoxicity of eleven naturally occurring compounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. MATERIALS AND METHODS: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) was measured by spectrophotometry. RESULTS: Chalcones: 2',4'-dihydroxy-6'-methoxychalcone (1); 4',6'-dihydroxy-2',5'-dimethoxychalcone (2); 2',4',6'-trihydroxy-5'-methoxychalcone (3); 2',6'-diacetate-4'-methoxychalcone (4), trachylobane diterpenoids: 2,6,19-trachylobanetriol; (ent-2α,6α)-form (10) and 2,18,19-trachylobanetriol; (ent-2α)-form (11) as well as doxorubicin displayed IC50 values below 110 µM in the six tested cancer cell lines. The IC50 values of the most active compounds were between 6.30 µM and 46.23 µM for compound 1 respectively towards breast adenocarcinoma MCF-7 cells and small lung cancer A549 cells and between 0.07 µM and 1.01 µM for doxorubicin respectively against SPC212 cells and A549 cells. Compounds 1 induced apoptosis in MCF-7 cells mediated by increasing ROS production and MMP loss. CONCLUSION: Chalcones 1-3 are potential cytotoxic phytochemicals that deserve more investigations to develop novel anticancer drugs against human carcinoma.
RESUMO
Four previously undescribed diterpenoids including two crotofolanes, crotodichogamoin A and B, and two halimanes, crothalimene A and B, a new sesquiterpenoid, and fifteen previously reported compounds, including the crotofolane, crotohaumanoxide, the casbane, depressin, a further seven furanohalimane diterpenoids, three patchoulane and two further cadinane sesquiterpenoids and aleuritolic acid were isolated from the root of Croton dichogamus. Crotodichogamoin B is an important biosynthetic intermediate of the crotofolane class and this is the first report of patchoulene sesquiterpenoids from the genus. Compounds were tested at one concentration, 1 × 10-5 M, in the NCI59 cell one-dose screen but did not show significant activity snd were also evaluated for their cytotoxicity against Caco-2 cell lines using the neutral red assay. 10-epi-Maninsigin D reduced Caco-2 cell viability at 10, 30 and 100 µM, with values of decreased viability of 28%, 48% and 43% respectively. None of the other tested compounds showed significant activity.
Assuntos
Croton/química , Diterpenos/farmacologia , Raízes de Plantas/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
A new ß-carboline alkaloid named sacleuximine A (1) together with known compounds palmatine (2), isotetrandrine (3), trans-N-feruloyltyramine (4), trans-N-caffeoyltyramine (5), yangambin (6), syringaresinol (7), sesamin (8), (+) epi-quercitol (9), 4-hydroxybenzaldehyde (10), ß-sitosterol (11), quercetin 3-O-rutinoside (12) and myricetin 3-O-ß-glucose (1â6) α-rhamnoside (13) have been isolated from methanol extract of Triclisia sacleuxii aerial parts. Compounds 1-10 were evaluated for their cytotoxicity against human adenocarcinoma (HeLa), human hepatocarcinoma (Hep3B) and human breast carcinoma (MCF-7) cells lines and also for antibacterial activities against both Gram-positive and Gram-negative bacteria. The cytotoxicity (IC50) values ranged between 0.15 and 36.7 µM while the minimum inhibitory concentrations were found to be in the range of 3.9 and 125 µM, respectively. This is the first report of antibacterial compounds and the isolation of lignans together with a ß-carboline alkaloid from T. sacleuxii.
Assuntos
Alcaloides/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carbolinas/isolamento & purificação , Menispermaceae/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Carbolinas/química , Carbolinas/farmacologia , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Componentes Aéreos da Planta/químicaRESUMO
BACKGROUND: Cancer is a major public health concern globally and chemotherapy remains the principal mode of the treatment of various malignant diseases. METHODS: This study was designed to investigate the cytotoxicity of 14 naturally occurring quinones including; 3 anthraquinones, 1 naphthoquinone and 10 benzoquinones against 6 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of the compounds, whilst caspase-Glo assay was used to detect caspases activation. Cell cycle and mitochondrial membrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygen species (ROS) were measured by spectrophotometry. RESULTS: Anthraquinone: emodin (2), naphthoquinone: plumbagin (4), and benzoquinones: rapanone (9), 2,5-dihydroxy-3-pentadecyl-2,5-cyclohexadiene-1,4-dione (10), 5-O-methylembelin (11), 1,2,4,5-tetraacetate-3-methyl-6-(14-nonadecenyl)-cyclohexadi-2,5-diene (13), as well as doxorubicin displayed interesting activities with IC50 values below 100 µM in the six tested cancer cell lines. The IC50 values ranged from 37.57 µM (towards breast adenocarcinoma MCF-7 cells) to 99.31 µM (towards small cell lung cancer A549 cells) for 2, from 0.06 µM (MCF-7 cells) to 1.14 µM (A549 cells) for 4, from 2.27 µM (mesothelioma SPC212 cells) to 46.62 µM (colorectal adenocarcinoma DLD-1 cells) for 9, from 8.39 µM (SPC212 cells) to 48.35 µM (hepatocarinoma HepG2 cells) for 10, from 22.57 µM (MCF-7 cells) to 61.28 µM (HepG2 cells) for 11, from 9.25 µM (MCF-7 cells) to 47.53 µM (A549 cells) for 13, and from 0.07 µM (SPC212 cells) to 1.01 µM (A549 cells) for doxorubicin. Compounds 4 and 9 induced apoptosis in MCF-7 cells mediated by increased ROS production and MMP loss, respectively. CONCLUSION: The tested natural products and mostly 2, 4, 9, 10, 11 and 13 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.
Assuntos
Antineoplásicos Fitogênicos/toxicidade , Benzoquinonas/toxicidade , Naftoquinonas/toxicidade , Extratos Vegetais/toxicidade , Quinonas/toxicidade , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Benzoquinonas/química , Benzoquinonas/isolamento & purificação , Células CACO-2 , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Quênia/epidemiologia , Células MCF-7 , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Quinonas/química , Quinonas/isolamento & purificaçãoRESUMO
BACKGROUND: Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge. METHODS: Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed 'PhytCancer -Phytotherapy to Fight Cancer' (www.phyt-cancer.uni-mainz.de). As a starting point, we have chosen the topic "biopiracy", since we feel this is of pragmatic significance for scientists working with medicinal plants. RESULTS: It was argued that the patenting of herbs or natural products by pharmaceutical corporations disregarded the ownership of the knowledge possessed by the indigenous communities on how these substances worked. Despite numerous court decisions in U.S.A. and Europe, several international treaties, (e.g. from United Nations, World Health Organization, World Trade Organization, the African Unity and others), sharing of a rational set of benefits amongst producers (mainly pharmaceutical companies) and indigenous communities is yet a distant reality. In this paper, we present an overview of the legal frameworks, discuss some exemplary cases of biopiracy and bioprospecting as excellent forms of utilization of natural resources. CONCLUSIONS: We suggest certain perspectives, by which we as scientists, may contribute towards prevention of biopiracy and also to foster the fair utilization of natural resources. We discuss ways, in which the interests of indigenous people especially from developing countries can be secured.
Assuntos
Produtos Biológicos , Bioprospecção/ética , Indústria Farmacêutica/ética , Etnofarmacologia , Propriedade , Plantas Medicinais , Roubo , Países em Desenvolvimento , Cooperação Internacional , Patentes como AssuntoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Plants from Kenyan flora are traditionally used against many ailments, including cancer and related diseases. Cancer is characterized as a condition with complex signs and symptoms. Recently there are recommendations that ethnopharmacological usages such as immune and skin disorders, inflammatory, infectious, parasitic and viral diseases should be taken into account when selecting plants that treat cancer. AIM: The present study was aimed at investigating the cytotoxicity of a plethora of 145 plant parts from 91 medicinal plants, most of which are used in the management of cancer and related diseases by different communities in Kenya, against CCRF-CEM leukemia cell line. MATERIALS AND METHODS: Extracts from different plant parts (leaves, stems, stem bark, roots, root barks, aerial parts and whole herb) were obtained by cold percolation using different solvent systems, such as (1:1v/v) dichloromethane (CH2Cl2) and n-hexane (1), methanol (MeOH) and CH2Cl2 (2); neat MeOH (3), 5% H2O in MeOH (4) and with ethanol (EtOH, 5); their cytotoxicities were determined using the resazurin reduction assay against CCRF-CEM cells. RESULTS: At a single concentration of 10µg/mL, 12 out of 145 extracts exhibited more than 50% cell inhibition. These include samples from the root bark of Erythrina sacleuxii (extracted with 50% n-hexane-CH2Cl2), the leaves of Albizia gummifera, and Strychnos usambarensis, the stem bark of Zanthoxylum gilletii, Bridelia micrantha, Croton sylvaticus, and Albizia schimperiana; the root bark of Erythrina burttii and E. sacleuxii (extracted with 50% CH2Cl2-MeOH), the stem bark of B. micrantha and Z. gilletii (extracted using 5% MeOH-H2O) and from the berries of Solanum aculeastrum (extracted with neat EtOH). The EtOH extract of the berries of S. aculeastrum and A. schimperiana stem bark extract displayed the highest cytotoxicity towards leukemia CCRF-CEM cells, with IC50 values of 1.36 and 2.97µg/mL, respectively. Other extracts having good activities included the extracts of the stem barks of Z. gilletii and B. micrantha and leaves of S. usambarensis with IC50 values of 9.04, 9.43 and 11.09µg/mL, respectively. CONCLUSIONS: The results of this study provided information related to the possible use of some Kenyam medicinal plants, and mostly S. aculeastrum, A. schimperiana, C. sylvaticus, Z. gilletii, B. micrantha and S. usambarensis in the treatment of leukemia. The reported data helped to authenticate the claimed traditional use of these plants. However, most plants are used in combination as traditional herbal concoctions. Hence, the cytotoxicity of corresponding plant combinations should be tested in vitro to authenticate the traditional medical practitioners actual practices.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores do Crescimento/farmacologia , Leucemia/patologia , Extratos Vegetais/farmacologia , Plantas Medicinais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , QuêniaRESUMO
BACKGROUND: Combretum zeyheri, belongs to the family Combretaceae and is one of the most popular herbal plants in tropical and subtropical countries. The leaves of Combretum zeyheri have been used as herbal medicine and have been reported to have pharmacological activity which includes anti-bacterial, anti-fungal, anticancer and antioxidant properties. The goal of this study was to isolate, identify and characterize compounds from C. zeyheri leaves which are responsible for its antifungal activity. METHODS: The preliminary isolation of C. zeyheri active compounds was carried out using chromatographic techniques which include sephadex gel column chromatography, silica gel column chromatography and thin-layer chromatography (TLC). The isolated compounds were then investigated for their antifungal activity using broth dilution assay. The combined effect of the most potent compound and an antifungal drug miconazole was investigated using the checkerboard assay. Time-kill assays were conducted for the combinations using the colony counting method. The mechanism of action of 5-hydroxy-7,4'-dimethoxyflavone as a potent antifungal agent was investigated by determining its inhibitory activity on Candida albicans drug efflux pumps using the ciprofloxacin assay. The ability of 5-hydroxy-7,4'-dimethoxyflavone to inhibit antioxidant enzymes as well as the biosynthesis of ergosterol were also investigated. RESULTS: A total of four pure compounds (A-D) were isolated from C. zeyheri leaf extract. Compound B (5-hydroxy-7,4'-dimethoxyflavone) was found to be active against Candida albicans using broth dilution method. This compound was also found to have synergistic activity on growth of C. albicans when combined with miconazole, completely inhibiting growth after only 4 hrs of incubation. Analysis of ergosterol content from Candida albicans showed a time-dependent decrease to 91 % and 63 % at 16 and 24 hrs respectively, in cells treated with ½ MIC of 5-hydroxy-7,4'-dimethoxyflavone. The compound 5-hydroxy-7,4'-dimethoxyflavone also showed inhibition of both the drug efflux pumps (with IC50 = 51.64 µg/ml) and the antioxidant enzymes (at 5 µM). CONCLUSION: The compound 5-hydroxy-7,4'-dimethoxyflavone may be partly responsible for the reported antifungal activity of C. zeyheri, and may serve as a potential source of lead compounds that can be developed as antifungal phytomedicines.
Assuntos
Antifúngicos/farmacologia , Apigenina/farmacologia , Candida albicans/efeitos dos fármacos , Combretum/química , Antifúngicos/análise , Antifúngicos/isolamento & purificação , Antioxidantes/análise , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apigenina/análise , Apigenina/isolamento & purificação , Cromatografia em Camada Fina , Testes de Sensibilidade Microbiana , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Folhas de Planta/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Turraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities. MATERIALS AND METHODS: From the stem bark of T. robusta six compounds, and from various parts of T. nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-(3)H, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2). RESULTS: The extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50<10 µg/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4 ± 0.03 µM and 1.1 ± 0.01 µM against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4-40.5 µM. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0 ± 0.03 and 8.4 ± 0.01 µM against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity. CONCLUSION: From the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices.
Assuntos
Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Limoninas/farmacologia , Meliaceae/química , Animais , Linhagem Celular Tumoral , Chlorocebus aethiops , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Limoninas/química , Limoninas/isolamento & purificação , Camundongos , Modelos Moleculares , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Células VeroRESUMO
Few studies have been undertaken on the relationship of the structure of flavones and neuroprotection. Previously, we described the structural determinants of the neuroprotective activity of some natural flavones in cerebellar granule neurons in culture against an oxidative insult (H2O2). In the present work, we analyzed anti-oxidant activity, cellular iron, and Ca(2+) levels and cellular bioavailability of neuroprotective and nonneuroprotective flavones in the same experimental paradigm. Oxidative cellular damage produced by H2O2 was prevented by all of the studied flavones with rather similar potency for all of them. Labile Iron Pool was neither affected by protective nor nonprotective flavones. Intracellular Ca(2+) homeostasis was not affected by protective flavones either. Nonetheless, fisetin, the nonprotective flavone, decreased Ca(2+) levels modifying Ca(2+) homeostasis. Methylation of the catechol group, although weakens anti-oxidant capacity, keeps the neuroprotective capacity with less degradation and lower toxicity, constituting promising structural alternatives as leads for the design of neuroprotective molecules.
Assuntos
Antioxidantes/farmacologia , Cálcio/metabolismo , Flavonoides/farmacologia , Ferro/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Células Cultivadas , Cerebelo/citologia , Flavonoides/química , Flavonoides/farmacocinética , Peróxido de Hidrogênio/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais , Ratos Sprague-Dawley , Espécies Reativas de OxigênioRESUMO
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
The CH2Cl2-MeOH (1:1) extract of the aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, showed activity against chloroquine sensitive D6 (IC50 9.7 microg/mL) and chloroquine resistant W2 (IC50 15.0 microg/mL) strains of Plasmodium falciparum. Seventeen secondary metabolites were isolated from the extract through conventional chromatographic techniques and identified using various spectroscopic methods. The compounds were evaluated for their in vitro antiplasmodial, antileishmanial and anticancer activities revealing activity of four carvotacetone derivatives, namely 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1), 3,7-dihydroxy-5-tigloyloxycarvotacetone (2), 3-acetoxy-5,7-dihydroxycarvotacetone (3) and 3,5,7-trihydroxy-carvotacetone (4); with antiplasmodial IC50 values of 1.40, 0.79, 0.60 and 3.40 microg/mL, respectively, against chloroquine sensitive D6 strains of P. falciparum; antiplasmodial activity of IC50 2.00, 0.90, 0.68 and 2.80 microg/mL, respectively, against chloroquine resistant W2 strains of P. falciparum; antileishmanial IC50 values of 0.70, 3.00, 0.70 and 17.00 microg/mL, respectively, against the parasite L. donovanii promastigotes, and anticancer activity against human SK-MEL, KB, BT-549 and SK-OV-3 tumor cells, with IC50 values between <1.1 - 5.3 microg/mL for 1-3. In addition, cytotoxic effects of the active compounds were evaluated against monkey kidney fibroblasts (VERO) and pig kidney epithelial cells (LLC-PK11). The structures of carvotacetone derivatives were determined by 1D and 2D NMR spectroscopy; the absolute stereochemical configuration of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) was determined as 3R, 4R, 5S by circular dichroism, specific rotation, 1H NMR and 2D NMR ROESY and NOESY experiments.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antiparasitários/farmacologia , Asteraceae , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Animais , Asteraceae/química , Linhagem Celular Tumoral , HumanosRESUMO
The EtOH extract of Abrus schimperi (Fabaceae), collected in Kenya, demonstrated significant activity against Leishmania donovani promastigotes with IC50 value of 3.6 microg/mL. Bioassay-guided fractionation of CHCl3 fraction using Centrifugal Preparative TLC afforded two antiparasitic isoflavanquinones, namely amorphaquinone (1) and pendulone (2). They displayed IC50 values of 0.63 microg/mL and 0.43 microg/mL, respectively, against L. donovani promastigotes. Both the compounds were also evaluated against L. donovani axenic amastigotes and amastigotes in THPI macrophage cultures. In addition, compounds 1 and 2 showed antiplasmodial activity against Plasmodium falciparum D6 and W2 strains, while 2 displayed antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (each IC50 1.44 microg/mL). The 1H and 13C data of 1, not fully assigned previously, were unambiguously assigned using 1D and 2D NMR HMBC and HMQC experiments. In addition, the absolute stereochemistry of the isolated compounds 1 and 2 was revised as C-(3S) based on Circular Dichroism experiments. This appears to be the first report of amorphaquinone (1) and pendulone (2) from the genus Abrus.
Assuntos
Abrus/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Isoflavonas/isolamento & purificação , Quinonas/isolamento & purificação , Anti-Infecciosos/química , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Dicroísmo Circular , Humanos , Isoflavonas/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Quinonas/químicaRESUMO
Albizia schimperiana Oliv. (Leguminosae) is a tree distributed in the highland of Kenya, where it is used as a traditional medicine for the treatment of bacterial and parasitic infections, notably pneumonia and malaria, respectively. Bioassay guided isolation of the CH2Cl2-MeOH 1:1/ MeOH-H20 9:1 (mixed) extract of A. schimperiana afforded the new bioactive macrocyclic spermine alkaloid, namely 5,14-dimethylbudmunchiamine L1 (1) and three known budmunchiamine analogs 2-4. The structures of the compounds 1-4 were determined by 1D and 2D NMR data, including COSY, HMQC, and HMBC experiments, and ESI-HRMS. Compounds 1 and 3 exhibited significant in vitro antimicrobial activity against a panel of microorganisms, including C neoformans, methicillin-resistant S. aureus, E. coli, M. intracellulare, and A. fumigatus. In Saddition, they demonstrated strong in vitro antimalarial activities against chloroquine-susceptible (D6) and -resistant (W2) strains of Plasmodium falciparum with IC50s ranging from 120-270 ng/mL. Compounds 1-4 were also evaluated for cytotoxic activity against selected human cancer cell lines and mammalian kidney fibroblasts (VERO cells). It was observed that hydroxyl substitution of the side chain of the budmunchiamines dramatically reduced the cytotoxicity and antimicrobial activity of the alkaloids 2 and 4 without decreasing antimalarial activity.
Assuntos
Albizzia/química , Alcaloides/química , Alcaloides/farmacologia , Anti-Infecciosos/química , Antineoplásicos Fitogênicos/química , Antiparasitários/química , Animais , Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antiparasitários/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Fungos/efeitos dos fármacos , Humanos , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Espermina/química , Espermina/farmacologiaRESUMO
From the roots of the African plant Bulbine frutescens (Asphodelaceae), two unprecedented novel dimeric phenylanthraquinones, named joziknipholones A and B, possessing axial and centrochirality, were isolated, together with six known compounds. Structural elucidation of the new metabolites was achieved by spectroscopic and chiroptical methods, by reductive cleavage of the central bond between the monomeric phenylanthraquinone and -anthrone portions with sodium dithionite, and by quantum chemical CD calculations. Based on the recently revised absolute axial configuration of the parent phenylanthraquinones, knipholone and knipholone anthrone, the new dimers were attributed to possess the P-configuration (i.e., with the acetyl portions below the anthraquinone plane) at both axes in the case of joziknipholone A, whereas in joziknipholone B, the knipholone part was found to be M-configured. Joziknipholones A and B are active against the chloroquine resistant strain K1 of the malaria pathogen, Plasmodium falciparum, and show moderate activity against murine leukemic lymphoma L5178y cells.