RESUMO
Four previously unreported triterpenoid saponins named 3ß-hydroxy-23-oxours-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside G) (1), 23-O-acetyl-3ß-hydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside H) (2), ursolic acid 28-O-[α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranosyl] ester (mannioside I) (3), and 3ß-hydroxy-23-oxolup-20(29)-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside J) (4) were isolated as minor constituents from the EtOAc soluble fraction of the MeOH extract of the leaves of Schefflera mannii along with the known compounds 23-hydroxyursolic acid 28-O-ß-D-glucopyranosyl ester (5), ursolic acid 28-O-ß-D-glucopyranosyl ester (6), pulsatimmoside B (7) betulinic acid 28-O-[α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranosyl] ester (8), 23-hydroxy-3-oxo-urs-12-en-28-oic acid (9), hederagenin (10), ursolic acid (11), betulinic acid (12), and lupeol (13). Their structures were elucidated by a combination of 1D and 2D NMR analysis and mass spectrometry. The MeOH extract, the EtOAc and n-BuOH fractions, and some of the isolated compounds were evaluated for their antibacterial activity against four bacteria: Staphylococcus aureus ATCC1026, Staphylococcus epidermidis ATCC 35984, Escherichia coli ATCC10536, and Klepsiella pnemoniae ATCC13882. They were also screened for their antioxidant properties, but no significant results were obtained.
Assuntos
Antibacterianos , Saponinas , Triterpenos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Saponinas/química , Saponinas/farmacologia , Saponinas/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estrutura Molecular , Folhas de Planta/química , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Araliaceae/químicaRESUMO
Three new ursane-type triterpenes (1-3) and twenty-one known triterpenoids (4-24) were isolated from the methanolic extract of the whole plants of Potentilla chinensis. Their structures were elucidated by extensive spectroscopic analysis of 1D and 2D NMR (HSQC, HMBC, COSY and ROESY) and HRESIMS data. The bioassay screening revealed the inhibitory effects on nitric oxide production of compounds 2, 5, 7, 9, 10, and 13-24 in LPS-induced RAW264.7 macrophages.
Assuntos
Óxido Nítrico/antagonistas & inibidores , Triterpenos Pentacíclicos/farmacologia , Potentilla/química , Animais , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
Medicinal plants are valuable sources of different active constituents that are known to have important pharmacological activities including anticancer effects. Lupeol, a pentacyclic triterpenoid, present in many medicinal plants, has a wide range of biological activities. Although the anticancer activity of lupeol was reported, the published data are inconsistent and the clear mechanism of action has never been assigned. The current study aims at investigating the anticancer specificity and mechanism of lupeol isolated from Avicennia marina, which grows in the desert of the United Arab Emirates. The compound was purified by chromatography and identified by spectroscopy. Compared with a negative control, lupeol caused significant (p < .001) growth inhibitory activity on MCF-7 and Hep3B parental and resistant cells by 45%, 46%, 72%, and 35%, respectively. The mechanism of action of lupeol was further explored by measuring its effect on key players in cancer development and progression, BCL-2 anti-apoptotic and BAX pro-apoptotic proteins. Lupeol significantly (p < .01) downregulated BCL-2 gene expression in parental and resistant Hep3B cells by 33 and 3.5 times, respectively, contributing to the induction of apoptosis in Hep3B cells, whereas it caused no effect on BAX. Furthermore, the immunoblotting analysis revealed that lupeol cleaved the executioner caspase-3 into its active form. Interestingly, lupeol showed no significant effect on the proliferation of monocytes, whereas it caused an increase in the sub-G1 population and a reduction in the apoptosis rates of monocytes at 48 and 72 h, indicative of no immuno-inflammatory responses. Collectively, lupeol can be considered as promising effective and safe anticancer agent, particularly against Hep3B cancer cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Avicennia/química , Triterpenos Pentacíclicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Células MCF-7 , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Triterpenos Pentacíclicos/isolamento & purificação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Fatores de TempoRESUMO
Celastrus hindsii is a popular medicinal plant in Vietnam and Southeast Asian countries as well as in South America. In this study, an amount of 12.05 g of an α-amyrin and ß-amyrin mixture was isolated from C. hindsii (10.75 g/kg dry weight) by column chromatography applying different solvent systems to obtain maximum efficiency. α-Amyrin and ß-amyrin were then confirmed by gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR). The antioxidant activities of the α-amyrin and ß-amyrin mixture were determined via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays with IC50 of 125.55 and 155.28 µg/mL, respectively. The mixture exhibited a high potential for preventing gout by inhibiting a relevant key enzyme, xanthine oxidase (XO) (IC50 = 258.22 µg/mL). Additionally, an important enzyme in skin hyperpigmentation, tyrosinase, was suppressed by the α-amyrin and ß-amyrin mixture (IC50 = 178.85 µg/mL). This study showed that C. hindsii is an abundant source for the isolation of α-amyrin and ß-amyrin. Furthermore, this was the first study indicating that α-amyrin and ß-amyrin mixture are promising in future therapies for gout and skin hyperpigmentation.
Assuntos
Antioxidantes/farmacologia , Celastrus/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Ácido Oleanólico/análogos & derivados , Triterpenos Pentacíclicos/isolamento & purificação , Folhas de Planta/química , Xantina Oxidase/antagonistas & inibidores , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cromatografia Gasosa-Espectrometria de Massas , Monofenol Mono-Oxigenase/metabolismo , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Triterpenos Pentacíclicos/química , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Xantina Oxidase/metabolismoRESUMO
Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters' stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25-100 µg/mL) and plasma (LOQ: 5-125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relatively low hepatic microsomal metabolism (<23%) after 1 h, which was significantly higher in the lowest concentration of C-27 esters (15 µM) (>40% degradation). Metabolic HPLC-PDA-HRMS studies suggested hydrolysis, hydroxylation, dehydration, O-methylation, hydroxylation and/or the reduction of hydrolyzed derivatives, depending on the concentration and the position of the ester link. Further permeability and absorption studies are required to better define triterpenic esters pharmacokinetic and specific formulations designed to increase their oral bioavailability.
Assuntos
Antiparasitários/química , Triterpenos Pentacíclicos/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Antiparasitários/farmacologia , Cromatografia Líquida de Alta Pressão , Ésteres/química , Ésteres/farmacologia , Hidrólise/efeitos dos fármacos , Triterpenos Pentacíclicos/isolamento & purificação , Extratos Vegetais/química , Plantas Medicinais/parasitologiaRESUMO
The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.
Assuntos
Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Cissus/química , Proteínas de Neoplasias/genética , Transcriptoma , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apigenina/química , Apigenina/isolamento & purificação , Apigenina/farmacologia , Bioensaio , Sobrevivência Celular/efeitos dos fármacos , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonas/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Perfilação da Expressão Gênica , Humanos , Quempferóis/química , Quempferóis/isolamento & purificação , Quempferóis/farmacologia , Masculino , Análise em Microsséries , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Células PC-3 , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Resveratrol/química , Resveratrol/isolamento & purificação , Resveratrol/farmacologia , Ácido BetulínicoRESUMO
Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.
Assuntos
Antioxidantes/farmacologia , Betula/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Acetaldeído/antagonistas & inibidores , Acetaldeído/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Betula/classificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Malondialdeído/antagonistas & inibidores , Camundongos , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Casca de Planta/classificação , Extratos Vegetais/química , Polônia , Superóxidos/antagonistas & inibidores , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman's spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.
Assuntos
Centella/química , Inibidores da Colinesterase/farmacologia , Triterpenos Pentacíclicos/farmacologia , Triterpenos/isolamento & purificação , Inibidores da Colinesterase/química , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Concentração Inibidora 50 , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Triterpenos Pentacíclicos/isolamento & purificação , Fisostigmina/farmacologia , Extratos Vegetais/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
A series of two new and twenty earlier synthesized branched extra-amino-triterpenoids obtained by the direct coupling of betulinic/betulonic acids with polymethylenpolyamines, or by the cyanoethylation of lupane type alcohols, oximes, amines, and amides with the following reduction were evaluated for cytotoxicity toward the NCI-60 cancer cell line panel, α-glucosidase inhibitory, and antimicrobial activities. Lupane carboxamides, conjugates with diaminopropane, triethylenetetramine, and branched C3-cyanoethylated polyamine methyl betulonate showed high cytotoxic activity against most of the tested cancer cell lines with GI50 that ranged from 1.09 to 54.40 µM. Betulonic acid C28-conjugate with triethylenetetramine and C3,C28-bis-aminopropoxy-betulin were found to be potent micromolar inhibitors of yeast α-glucosidase and to simultaneously inhibit the endosomal reticulum α-glucosidase, rendering them as potentially capable to suppress tumor invasiveness and neovascularization, in addition to the direct cytotoxicity. Plausible mechanisms of cytotoxic action and underlying disrupted molecular pathways were elucidated with CellMinner pattern analysis and Gene Ontology enrichment analysis, according to which the lead compounds exert multi-target antiproliferative activity associated with oxidative stress induction and chromatin structure alteration. The betulonic acid diethylentriamine conjugate showed partial activity against methicillin-resistant S. aureus and the fungi C. neoformans. These results show that triterpenic polyamines, being analogs of steroidal squalamine and trodusquemine, are important substances for the search of new drugs with anticancer, antidiabetic, and antimicrobial activities.
Assuntos
Proliferação de Células/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Triterpenos/farmacologia , alfa-Glucosidases/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Linhagem Celular Tumoral , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Neoplasias/tratamento farmacológico , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Red dragon fruit (Hylocereus polyrhizus, (F.A.C. Weber) Britton and Rose) has been reported to have various biological activities such as antimicrobial, anti-hypercholesterolemia, anti-diabetes mellitus, cardiovascular risk reduction, health supplement, and melanoma cell inhibitory. The red thick peel of this fruit is just practically a waste that is possibly utilized to maintain health, therefore this research aimed to isolate and identify active compounds of H. Polyrhizus peels which can improve the immune system of body. In order to simplify methanol extract was partition and fractionation. The active compounds of petroleum ether fraction were separated and purified using preparative thin layer chromatography. The identification of the compounds structure was conducted through spectroscopic techniques, including UV, FT-IR, 13CNMR and 1HNMR spectroscopy. The data of spectra revealed that the isolate is lupeol. The statistical analysis of macrophage activity showed that the isolate with concentrations of 100, 50, 25, 12.5 and 6.25µg/mL could activate the macrophages higher than control negative. Terpenoid generated from the isolation of Hylocereus polyrhizus was identified as lupeol (1-isopropenyl-3a,5a,5b,8,8,11a-hexamethyl-eicosahydrocyclopenya [α] chrysen-9ol. In vitro test shows that the isolated compound had an immunomodulatory activity by increases macrophage phagocytosis of latex beads.
Assuntos
Cactaceae , Fatores Imunológicos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Células Cultivadas , Frutas , Fatores Imunológicos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Triterpenos Pentacíclicos/isolamento & purificação , Fagócitos/efeitos dos fármacos , Fagócitos/imunologia , Extratos Vegetais/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Terpenos/isolamento & purificaçãoRESUMO
Lantana camara is an important medicinal plant that contains many active compounds, including pentacyclic triterpenoids, with numerous biological activities. The present study was conducted to evaluate the anti-oxidant, anti-tumour, and cell cycle arrest properties of chemical compounds extracted from L. camara leaves. Four compounds were identified after subjecting the plant methanolic extract to LC-MS/MS analysis: lantadene A, lantadene B, icterogenin, and lantadene C. Potential antioxidant activity was examined using 2, 2-diphenyl-1-picrylhydrazyl and compared with vitamin C as a control. Lantadene A and B were confirmed to possess the highest scavenging activity, while icterogenin and lantadene C exhibited a lesser antioxidant effect. All extracted compounds exerted a dose-dependent reduction in MCF-7 cell viability; however, lantadene B showed the highest anti-cancer activity, with an IC50 of 112.2 µg mL-1, and was therefore used in subsequent experiments. The results also confirmed the significant release of caspase 9 in a dose-dependent pattern following treatment of MCF-7 cells with a range of lantadene B concentrations. Lantadene B was found to induce MCF-7 cell cycle arrest in G1, blocking the G1/S transition with a maximum significant (p ≤ 0.01) cell count of 80.35% at 25 µg mL-1. No significant changes were observed in S phase, but a decrease in the MCF-7 population was exhibited in G2/M phase.
Assuntos
Lantana/metabolismo , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Antioxidantes/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cromatografia Líquida , Humanos , Lantana/fisiologia , Células MCF-7/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/isolamento & purificação , Extratos Vegetais/química , Folhas de Planta/química , Espectrometria de Massas em Tandem , Triterpenos/farmacologiaRESUMO
Plant extracts from the genus Cecropia have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous results have shown that roots of Cecropia telenitida contain pentacyclic triterpenes and these molecules display a hypoglycemic effect in an insulin-resistant murine model. The pharmacological target of these molecules, however, remains unknown. Several lines of evidence indicate that pentacyclic triterpenes inhibit the 11ß-hydroxysteroid dehydrogenase type 1 enzyme, which highlights the potential use of this type of natural product as phytotherapeutic or botanical dietary supplements. The main goal of the study was the evaluation of the inhibitory effect of Cecropia telenitida molecules on 11ß-hydroxysteroid dehydrogenase type 1 enzyme activity. A pre-fractionated chemical library was obtained from the roots of Cecropia telenitida using several automated chromatography separation steps and a homogeneous time resolved fluorescence assay was used for the bio-guided isolation of inhibiting molecules. The screening of a chemical library consisting of 125 chemical purified fractions obtained from Cecropia telenitida roots identified one fraction displaying 82% inhibition of the formation of cortisol by the 11ß-hydroxysteroid dehydrogenase type 1 enzyme. Furthermore, a molecule displaying IC50 of 0.95 ± 0.09 µM was isolated from this purified fraction and structurally characterized, which confirms that a pentacyclic triterpene scaffold was responsible for the observed inhibition. Our results support the hypothesis that pentacyclic triterpene molecules from Cecropia telenitida can inhibit 11ß-hydroxysteroid dehydrogenase type 1 enzyme activity. These findings highlight the potential ethnopharmacological use of plants from the genus Cecropia for the treatment of metabolic disorders and diabetes.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Urticaceae/química , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Ensaios de Triagem em Larga Escala , Humanos , Medicina Tradicional , Estrutura Molecular , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Extratos Vegetais/química , Raízes de Plantas/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/isolamento & purificação , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D (1), 12-epi-crotocorylifuran (5), cluytyl-ferulate (6), hexacosanoyl- ferulate (7), vanillin (8), acetyl-aleuritolic acid (9) and lupeol (10), were also isolated. The structures of the isolated compounds (1-10) were elucidated by spectroscopic means. The cytotoxicity of compounds 1-10 was assessed against A549, MCF7, PC3 and PNT2 cell lines using the MTT assay. Compounds 1 and 2 showed moderate levels of activity against both A549 and MCF7 cells with 1 being the most active with IC50 values of 63.8 ± 13.8 and 136.2 ± 22.7 µM against A549 and MCF7 cells, respectively. The epimeric mixture of 3 and 4 was moderately active against A549 and PC3 cells (IC50 = 128.6 ± 31.0 and 111.2 ± 2.9 µM, respectively).
Assuntos
Antineoplásicos Fitogênicos/química , Croton/química , Citotoxinas/química , Diterpenos Clerodânicos/química , Furanos/química , Triterpenos Pentacíclicos/química , Casca de Planta/química , Células A549 , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Diterpenos Clerodânicos/isolamento & purificação , Diterpenos Clerodânicos/farmacologia , Furanos/isolamento & purificação , Furanos/farmacologia , Humanos , Concentração Inibidora 50 , Células MCF-7 , Estrutura Molecular , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/químicaRESUMO
A protocol was established to produce bioactive compounds in a callus culture of Ageratina pichinchensis by using 1 mg L-1 NAA with 0.1 mg L-1 KIN. The phytochemical study of the EtOAc extract obtained from the callus biomass, allowed the isolation and characterization of eleven secondary metabolites, of which dihydrobenzofuran (5) and 3-epilupeol (7), showed important anti-inflammatory activity. Compound 5 inhibits in vitro the secretion of NO (IC50 = 36.96 ± 1.06 µM), IL-6 (IC50 = 73.71 ± 3.21 µM), and TNF-α (IC50 = 73.20 ± 5.99 µM) in RAW (Murine macrophage cells) 264.7 macrophages, as well as the activation of NF-κB (40% at 150 µM) in RAW-blue macrophages, while compound 7 has been described that inhibit the in vivo TPA-induced ear edema, and the in vitro production of NO, and the PLA2 enzyme activity. In addition, quantitative GC-MS analysis showed that the anti-inflammatory metabolites 5 and 7 were not detected in the wild plant. Overall, our results indicated that A. pichinchensis can be used as an alternative biotechnological resource for obtaining anti-inflammatory compounds. This is the first report of the anti-inflammatory activity of compound 5 and its production in a callus culture of A. pichinchensis.
Assuntos
Ageratina/química , Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Edema/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Benzofuranos/isolamento & purificação , Técnicas de Cultura , Orelha , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Etanol/química , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Cinetina/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Ácidos Naftalenoacéticos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Triterpenos Pentacíclicos/isolamento & purificação , Fosfolipases A2/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Células RAW 264.7 , Metabolismo Secundário/efeitos dos fármacos , Solventes/química , Acetato de Tetradecanoilforbol/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Seven derivatives of pentacyclic triterpene acids (1-7) were isolated from the bark of Alnus viridis ssp. viridis using a combination of column chromatography and semipreparative HPLC. Compounds 1-3, 6, and 7 were determined to be new after spectroscopic data interpretation and were assigned as 27-hydroxyalphitolic acid derivatives (1-3), a 27-hydroxybetulinic acid derivative (6), and a 3-epi-maslinic acid derivative (7), respectively. Pentacyclic triterpenoids with a C-27 hydroxymethyl group have been found in species of the genus Alnus for the first time. These compounds were subjected to cytotoxicity testing against a number of cancer cell lines. Also, selected pentacyclic triterpenoids were selected as potential inhibitors of topoisomerases I and IIα for an in silico investigation.
Assuntos
Linhagem Celular/efeitos dos fármacos , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Casca de Planta/química , Inibidores da Topoisomerase/isolamento & purificação , Inibidores da Topoisomerase/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Alnus/química , Linhagem Celular/química , Humanos , Estrutura Molecular , Triterpenos Pentacíclicos/química , Inibidores da Topoisomerase/química , Triterpenos/químicaRESUMO
Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with ß-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with ß-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.
Assuntos
Antibacterianos/farmacologia , Antidiarreicos/farmacologia , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Maytenus/química , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/farmacologia , Antibacterianos/isolamento & purificação , Antidiarreicos/isolamento & purificação , Antivirais/isolamento & purificação , Linhagem Celular , Maytenus/classificação , Triterpenos Pentacíclicos/isolamento & purificaçãoRESUMO
Natural steroids and triterpenes such as b-sitosterol, stigmasterol, lupeol, ursolic and betulinic acids were transformed into its hexanoic and oleic esters, to evaluate the influence of chemical modification towards the cytotoxic activities against tumor cells. The derivatives were evaluated against five tumor cell lines [OVCAR-8 (ovarian carcinoma); SF-295 (glioblastoma); HCT-116 (colon adenocarcinoma); HL-60 (leukemia); and PC-3 (prostate carcinoma)] and the results showed only betulinic acid hexyl ester exhibits cytotoxic potential activity.
Assuntos
Antineoplásicos/farmacologia , Fabaceae/química , Lamiaceae/química , Triterpenos Pentacíclicos/farmacologia , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres , Fabaceae/classificação , Humanos , Concentração Inibidora 50 , Lamiaceae/classificação , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação , Ácido Betulínico , Ácido UrsólicoRESUMO
Six new pentacyclic triterpenoids were isolated from the fruit of Camptotheca acuminata. The chemical structures of the new compounds were elucidated by extensive spectroscopic analysis including HR-ESI-MS, IR, UV, 1D- and 2D-NMR. Moreover, the antibacterial activities of compounds 1, 2, 4, 5, and 6 were evaluated against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Dickeya zeae. All these tested compounds showed moderate antibacterial activity against Bacillus subtilis and Dickeya zeae.
Assuntos
Antibacterianos/isolamento & purificação , Camptotheca/química , Triterpenos Pentacíclicos/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Frutas/química , Estrutura Molecular , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologiaRESUMO
Ten novel oleanolic acid (OA) derivatives were synthesized through modifications at positions of A ring and C-28. Inhibitory activities of the oleanolic acid derivatives against SGC7901 and A549 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The lab results revealed that all these compounds displayed some antitumor activity against SGC-7901 and A-549 cell lines. Among them, II4 and II5 exhibited excellent antitumor activities against SGC7901 cells and A549 cells, compared with gefitinib. Molecular docking studies have shown that compounds II4 and II5 produce potent antitumor activities by interacting with C-kit receptor through hydrogen bonds and hydrophobic bonds.
Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Ácido Oleanólico , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Células A549 , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Gefitinibe , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Triterpenos Pentacíclicos/química , Proteínas Proto-Oncogênicas c-kit/metabolismo , Quinazolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
CONTEXT: Traditionally, Rhododendron arboreum Sm. (Ericaceae) is a very important medicinal plant having oxytocic, estrogenic, anti-inflammatory, analgesic and hepatoprotective activities; it also inhibits the prostaglandin synthetase. OBJECTIVES: This study determines the cytotoxic potential of 15-oxoursolic acid isolated from R. arboreum against selected human cancer cell lines. MATERIALS AND METHODS: Extraction from stem bark (5 kg) of R. arboreum was performed with methanol, which was successively partitioned into hexane, dichloromethane and ethyl acetate fractions, respectively. The new antitumor agent [15-oxoursolic acid (1)] was isolated from ethyl acetate fraction through column chromatography. Structure elucidation of new compound was performed through extensive spectroscopy i.e., IR, MS and 1D and 2D NMR. Cytotoxicity of isolated compound was determined at doses 5-100 µM for a period of 72 h on specified human cancer cell lines [renal cell carcinoma (A498), non-small cell lung (NCI-H226), squamous cell carcinoma (H157) and human ovarian carcinoma (MDR-2780AD)]. RESULTS: Structure of isolated compound was characterized as 15-oxoursolic acid on the basis of various extensive spectroscopic techniques. 15-Oxoursolic acid revealed considerable anticancer activity with IC50 values of 2.3 ± 0.1 µM, 4.9 ± 0.2 µM, 9.2 ± 0.2 µM and 10.3 ± 0.1 µM against MDR 2780AD, Hep G2, H157 and NCI-H226, respectively, while in the case of A498, the activity was good (IC50 32.8 ± 1.2 µM). CONCLUSIONS: This study highlighted the potential of 15-oxoursolic acid to be further explored as a new lead compound for cancer chemotherapy.