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1.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361745

RESUMO

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Camellia sinensis/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vitis/química , Withania/química , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Flavonoides/química , Flavonoides/isolamento & purificação , Células Hep G2 , Humanos , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Folhas de Planta/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sementes/química , Transdução de Sinais , Taninos/química , Taninos/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação , alfa-Amilases/genética , alfa-Amilases/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
2.
Mar Drugs ; 18(6)2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32585891

RESUMO

The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus Agelas, display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge A. dilatata from the coastal area of the Yucatan Peninsula (Mexico). In this study, we isolated eight known alkaloids from an organic extract of the sponge. We used NMR and MS analysis and comparison with existing databases to characterize the alkaloids: ageliferin (1), bromoageliferin (2), dibromoageliferin (3), sceptrin (4), nakamuric acid (5), 4-bromo-1H-pyrrole-2-carboxylic acid (6), 4,5-dibromopyrrole-2-carboxylic acid (7) and 3,7-dimethylisoguanine (8). We also evaluated, for the first time, the activity of these alkaloids against the most problematic multidrug-resistant (MDR) pathogens, i.e., the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Bromoageliferin (2) displayed significant activity against P. aeruginosa. Comparison of the antibacterial activity of ageliferins 1-3 (of similar structure) against P. aeruginosa revealed some relationship between structure and activity. Furthermore, in in vitro assays, 2 inhibited growth and biofilm production in clinical strains of P. aeruginosa. Moreover, 2 increased the survival time in an in vivo Galleria mellonella model of infection. The findings confirm bromoageliferin (2) as a potential lead for designing new antibacterial drugs.


Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Poríferos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/crescimento & desenvolvimento , Agelas/química , Alcaloides/isolamento & purificação , Animais , Biofilmes , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento , México , Estrutura Molecular , Pseudomonas aeruginosa/crescimento & desenvolvimento
3.
Nutrients ; 12(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32369976

RESUMO

Coffee consumption has been related to a preventive effect against several non-transmissible pathologies. Due to the content of this beverage in phytochemicals and minerals, it has been proposed that its impact on health may partly depend on gut microbiota modulation. Our aim was to explore the interaction among gut microbiota, fecal short chain fatty acids, and health-related parameters in 147 healthy subjects classified according to coffee consumption, to deepen the association of the role of the (poly)phenol and alkaloid content of this beverage. Food daily intake was assessed by an annual food frequency questionnaire (FFQ). Coffee consumption was categorized into three groups: non-coffee-consumers (0-3 mL/day), moderate consumers (3-45 mL/day) and high-coffee consumers (45-500 mL/day). Some relevant groups of the gut microbiota were determined by qPCR, and concentration of fecal short chain fatty acids by gas chromatography. Serum health related biomarkers were determined by standardized methods. Interestingly, a higher level of Bacteroides-Prevotella-Porphyromonas was observed in the high consumers of coffee, who also had lower levels of lipoperoxidation. Two groups of coffee-derived (poly)phenol, methoxyphenols and alkylphenols, and caffeine, among alkaloids, were directly associated with Bacteroides group levels. Thus, regular consumption of coffee appears to be associated with changes in some intestinal microbiota groups in which dietary (poly)phenol and caffeine may play a role.


Assuntos
Alcaloides/farmacologia , Cafeína/farmacologia , Café/química , Café/fisiologia , Suplementos Nutricionais , Ingestão de Alimentos/fisiologia , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Voluntários Saudáveis , Benefícios do Seguro , Minerais/farmacologia , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcaloides/isolamento & purificação , Cafeína/isolamento & purificação , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Minerais/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Polifenóis/isolamento & purificação , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
4.
J Sep Sci ; 40(23): 4482-4494, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28960719

RESUMO

A novel, improved, and comprehensive method for quality evaluation and discrimination of Herba Leonuri has been developed and validated based on normal- and reversed-phase chromatographic methods. To identify Herba Leonuri, normal- and reversed-phase high-performance thin-layer chromatography fingerprints were obtained by comparing the colors and Rf values of the bands, and reversed-phase high-performance liquid chromatography fingerprints were obtained by using an Agilent Poroshell 120 SB-C18 within 28 min. By similarity analysis and hierarchical clustering analysis, we show that there are similar chromatographic patterns in Herba Leonuri samples, but significant differences in counterfeits and variants. To quantify the bio-active components of Herba Leonuri, reversed-phase high-performance liquid chromatography was performed to analyze syringate, leonurine, quercetin-3-O-robiniaglycoside, hyperoside, rutin, isoquercitrin, wogonin, and genkwanin simultaneously by single standard to determine multi-components method with rutin as internal standard. Meanwhile, normal-phase high-performance liquid chromatography was performed by using an Agilent ZORBAX HILIC Plus within 6 min to determine trigonelline and stachydrine using trigonelline as internal standard. Innovatively, among these compounds, bio-active components of quercetin-3-O-robiniaglycoside and trigonelline were first determined in Herba Leonuri. In general, the method integrating multi-chromatographic analyses offered an efficient way for the standardization and identification of Herba Leonuri.


Assuntos
Alcaloides/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Glucosídeos/isolamento & purificação , Leonurus/química , Quercetina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Medicamentos de Ervas Chinesas/normas , Controle de Qualidade , Quercetina/isolamento & purificação
5.
PLoS One ; 11(8): e0161146, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27529425

RESUMO

The present study demonstrated the use of the Linear Quantitative Profiling Method (LQPM) to evaluate the quality of Alkaloids of Sophora flavescens (ASF) based on chromatographic fingerprints in an accurate, economical and fast way. Both linear qualitative and quantitative similarities were calculated in order to monitor the consistency of the samples. The results indicate that the linear qualitative similarity (LQLS) is not sufficiently discriminating due to the predominant presence of three alkaloid compounds (matrine, sophoridine and oxymatrine) in the test samples; however, the linear quantitative similarity (LQTS) was shown to be able to obviously identify the samples based on the difference in the quantitative content of all the chemical components. In addition, the fingerprint analysis was also supported by the quantitative analysis of three marker compounds. The LQTS was found to be highly correlated to the contents of the marker compounds, indicating that quantitative analysis of the marker compounds may be substituted with the LQPM based on the chromatographic fingerprints for the purpose of quantifying all chemicals of a complex sample system. Furthermore, once reference fingerprint (RFP) developed from a standard preparation in an immediate detection way and the composition similarities calculated out, LQPM could employ the classical mathematical model to effectively quantify the multiple components of ASF samples without any chemical standard.


Assuntos
Alcaloides/análise , Cromatografia/métodos , Sophora/química , Alcaloides/química , Alcaloides/isolamento & purificação , Cromatografia/economia , Modelos Lineares , Reprodutibilidade dos Testes , Fatores de Tempo
6.
PLoS One ; 9(11): e111999, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25405606

RESUMO

The fruits of Solanum lycocarpum, known as wolf-fruit, are used in folk medicine, and because of that we have evaluated both the genotoxic potential of its glycoalkaloidic extract (SL) and its influence on the genotoxicity induced by methyl methanesulfonate. Furthermore, the potential blocking effect of SL intake in the initial stage of colon carcinogenesis in Wistar rats was investigated in a short-term (4-week) bioassay using aberrant crypt foci (ACF) as biomarker. The genotoxic potential was evaluated using the Swiss mice peripheral blood micronucleus test. The animals were treated with different doses of SL (15, 30 and 60 mg/kg b.w.) for 14 days, and the peripheral blood samples were collected at 48 h, 7 days and 14 days after starting the treatment. For antigenotoxicity assessment, MMS was administered on the 14th day, and after 24 h the harvesting of bone marrow and liver cells was performed, for the micronucleus and comet assays, respectively. In the ACF assay, male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg b.w.), twice a week, during two weeks to induce ACF. The treatment with SL (15, 30 and 60 mg/kg b.w.) was given for four weeks during and after carcinogen treatment to investigate the potential beneficial effects of SL on DMH-induced ACF. The results demonstrated that SL was not genotoxic in the mouse micronucleus test. In animals treated with SL and MMS, the frequencies of micronucleus and extensions of DNA damage were significantly reduced in comparison with the animals receiving only MMS. Regarding the ACF assay, SL significantly reduced the frequency of ACF induced by DMH.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Dano ao DNA , Frutas/química , Extratos Vegetais/farmacologia , Solanum/química , Focos de Criptas Aberrantes/tratamento farmacológico , Alcaloides/isolamento & purificação , Alcaloides/uso terapêutico , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/uso terapêutico , Células da Medula Óssea/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar
7.
Chirality ; 26(8): 411-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24909415

RESUMO

In the last years the identification of new legal and illegal highs has become a huge challenge for the police and prosecution authorities. In an analytical context, only a few analytical methods are available to identify these new substances. Moreover, many of these recreational drugs are chiral and it is supposed that the enantiomers differ in their pharmacological potency. Since nonenantioselective synthesis is easier and cheaper, they are mainly sold as racemic mixtures. The goal of this research work was to develop an inexpensive method for the chiral separation of cathinones and amphetamines. This should help to discover if the substances are sold as racemic mixtures and give further information about their quality as well as their origin. Chiral separation of a set of 6 amphetamine and 25 cathinone derivatives, mainly purchased from various Internet shops, is presented. A LiChrospher 100 RP-18e, 250 x 4 mm, 5 µm served as the stationary phase. The chiral mobile phase consisted of methanol, water, and sulfated ß-cyclodextrin. Measurements were performed under isocratic conditions in reversed phase mode using UV detection. Four model compounds of the two substance classes were used to optimize the mobile phase. Under final conditions (methanol:water 2.5:97.5 + 2% sulfated ß-cyclodextrin) enantiomers of amphetamine and five derivatives were baseline separated within 23 min. In all, 17 cathinones were completely or partially chirally separated. However, as only 3 of 25 cathinones were baseline resolved, the application of this method is limited for cathinone analogs. Additionally, the results were compared with an RP-8e column.


Assuntos
Alcaloides/química , Alcaloides/isolamento & purificação , Anfetamina/química , Anfetamina/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , beta-Ciclodextrinas/química , Cromatografia Líquida de Alta Pressão/economia , Cromatografia de Fase Reversa , Espectrofotometria Ultravioleta , Estereoisomerismo
8.
Planta Med ; 80(2-3): 231-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24452459

RESUMO

A new aconitane alkaloid, 1-O-demethylswatinine (1), was isolated from the root of Aconitum moldavicum together with the known compounds cammaconine (2), columbianine (3), swatinine (4), gigactonine (5), delcosine (6), lycoctonine (7), and ajacine (8). The structures were established by means of HRESIMS, 1D and 2D NMR spectroscopy, including 1H-1H COSY, NOESY, HSQC, and HMBC experiments, resulting in complete 1H-NMR chemical shift assignments for 1-4. The effects of the isolated compounds 4-8, together with eighteen other Aconitum diterpene and norditerpene alkaloids with different skeletal types and substitution patterns, were studied on Nav 1.2 channels by the whole-cell patch clamp technique, using the QPatch-16 automated patch clamp system. Pyroaconitine, ajacine, septentriodine, and delectinine demonstrated significant Nav 1.2 channel inhibition (57-42 %) at 10 µM concentration; several other compounds (acovulparine, acotoxicine, hetisinone, 14-benzoylaconine-8-O-palmitate, aconitine, and lycoctonine) exerted moderate inhibitory activity (30-22 %), while the rest of the tested alkaloids were considered to be inactive. On the basis of these results and by exhaustive comparison of data of previously published computerized QSAR studies on diterpene alkaloids, certain conclusions on the structure-activity relationships of Aconitum alkaloids concerning Nav 1.2 channel inhibitory activity are proposed.


Assuntos
Alcaloides/farmacologia , Diterpenos/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Células CHO , Cricetulus , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Técnicas de Patch-Clamp , Raízes de Plantas/química , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/isolamento & purificação , Relação Estrutura-Atividade
9.
Anal Chim Acta ; 797: 50-6, 2013 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-24050669

RESUMO

A glass liquid-liquid extraction (LLE) microchip with three parallel 3.5 cm long and 100 µm wide interconnecting channels was optimized in terms of more environmentally friendly (greener) solvents and extraction efficiency. In addition, the optimized chip was successfully hyphenated with nano-liquid chromatography with ultraviolet and mass spectrometric detection (nanoLC-UV-MS) for on-line analysis. In this system, sample pretreatment, separation and detection are integrated, which significantly shortens the analysis time, saves labor and drastically reduces solvent consumption. Strychnine was used as model analyte to determine the extraction efficiency of the optimized 3-phase chip. Influence of organic solvent, pH of feed phase, type of alkaloid, and flow rates were investigated. The results demonstrated that the 3-phase chip nanoLC-UV/MS hyphenation combines rapid (~25 s) and efficient (extraction efficiency >90%) sample prep, with automated alkaloid analyses. The method was applied to real samples including Strychnos nux-vomica seeds, Cephaelis ipecacuanha roots, Atropa belladonna leaves, and Vinca minor leaves.


Assuntos
Alcaloides/isolamento & purificação , Cromatografia Líquida de Alta Pressão/instrumentação , Extração Líquido-Líquido/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Plantas/química , Acetatos/química , Cromatografia Líquida de Alta Pressão/economia , Desenho de Equipamento , Química Verde/economia , Química Verde/instrumentação , Extração Líquido-Líquido/economia , Técnicas Analíticas Microfluídicas/economia , Solventes/química
10.
Artigo em Inglês | MEDLINE | ID: mdl-23603295

RESUMO

The alkaloids of Piper longum L. (PLA) improved motor dysfunction and dopamine depletion in a rat model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. A rapid, accurate, simple, and high-performance liquid chromatography-mass spectrometry method was developed and fully validated to simultaneously detect three P. longum L. antiparkinsonian alkaloids (piperine (PPR), piperlonguminine (PPL), and Δα,ß-dihydropiperlonguminine (DPPL)) in rat plasma, heart, liver, spleen, lung, kidney, and brain tissues. Rat plasma and tissue homogenates were pretreated with methanol/acetonitrile (1:1, v/v) using a simple protein precipitation method. Chromatographic separation was achieved on a Phenomenex Gemini C18 column (50mm×2.00mm, 5µm) with a gradient mobile phase containing 0.1% (v/v) formic acid in water or acetonitrile. The elution was pumped at a flow rate of 0.4ml/min, and the injection volume was 10µl with a total running time of 4min. The analysis was performed by selected reaction monitoring of the transitions m/z 285.9→201.1, m/z 274.3→209.9, and m/z 276.2→134.9 for PPR, PPL, and DPPL, respectively. All three analytes showed good linearity (R>0.995) in plasma and tissue homogenates, and the lower limit of quantification was 0.20ng/ml. The distribution of PPR, PPL and DPPL in all 7 tissues was examined. The highest concentrations for PPR and PPL were observed in the liver, while the highest DPPL concentration was observed in the kidney. Following oral administration, the highest levels of PPR, PPL and DPPL in different tissues were found at approximately 2h. PPR, PPL and DPPL could cross the blood-brain barrier. The present study provides evidences for that PPR, PPL and DPPL may play roles in improving motor dysfunction and dopamine depletion.


Assuntos
Alcaloides/farmacocinética , Antiparkinsonianos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Piper/química , Extratos Vegetais/farmacocinética , Espectrometria de Massas em Tandem/métodos , Alcaloides/sangue , Alcaloides/isolamento & purificação , Animais , Antiparkinsonianos/sangue , Antiparkinsonianos/isolamento & purificação , Cromatografia Líquida de Alta Pressão/economia , Masculino , Extratos Vegetais/sangue , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/economia , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/economia , Distribuição Tecidual
11.
Pharm Biol ; 51(5): 550-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23368940

RESUMO

CONTEXT: Neuroprotective therapy to rescue dopaminergic neurons is an important trait in the management of Parkinson's disease (PD). OBJECTIVE: The present study identified and evaluated SFSE-T, a standardized hydroalcoholic extract of Trigonella foenum-graecum L. seeds (Fabaceae), in animal models of PD. MATERIALS AND METHODS: The identification of SFSE-T was carried out by high-performance liquid chromatography for the marker compound trigonelline (TGN). The effects of single dose oral treatment of SFSE-T (10, 30 or 100 mg/kg) were studied using animal models of PD, namely, 6-hydroxydopamine (6-OHDA)-induced unilateral lesions in rats, and 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice. The effects of SFSE-T on monoamino oxidase (MAO) enzyme in vitro as well as possible side effects of SFSE-T in vivo were also evaluated. RESULTS: The concentration of TGN in a test sample of SFSE-T was found to be 82%. SFSE-T (30 mg/kg, oral) showed a significant increase in the number of ipsilateral rotations (45.67 rotations in 30-min period) as compared with vehicle control group (no rotations) when tested in 6-OHDA-induced unilateral lesioned rats. SFSE-T (30 mg/kg, oral) showed significant reversal of motor dysfunction (spontaneous motor activity scores, speed, distance traveled and number of square crossed) caused by MPTP induced lesions in C57BL/6 mice in pretreatment (1 h) schedule but not in post-treatment (1 h) schedule. SFSE-T neither showed anticholinergic effects nor showed selective MAO-B enzyme inhibition in vitro. DISCUSSION AND CONCLUSION: SFSE-T showed reversal of motor symptoms in an animal model of PD probably through neuroprotective properties.


Assuntos
Antiparkinsonianos/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Extratos Vegetais/farmacologia , Trigonella/química , Administração Oral , Alcaloides/análise , Alcaloides/isolamento & purificação , Animais , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/fisiopatologia , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Sementes
12.
J Nat Prod ; 74(9): 1931-8, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21902195

RESUMO

On the basis of a comparison of 42 Stemona samples, representing eight different species collected and cultivated in Thailand, species-specific accumulation trends of Stemona alkaloids were analyzed. An overview was achieved by comparative HPLC analyses of methanolic crude extracts of underground parts coupled with diode array or evaporative light scattering detectors. All major compounds were isolated and their structures elucidated by NMR and MS analyses. Protostemonine- and stichoneurine-type derivatives dominated, from which the latter characterize S. tuberosa and S. phyllantha accumulating species-specific isomers of tuberostemonine (3). The widespread S. curtisii and S. collinsiae clearly deviate by protostemonine-type derivatives dominated by stemofoline (10) and/or didehydrostemofoline (11). Further diversification within this structural type results from a mutual accumulation of derivatives with a pyrrolo- or pyridoazepine nucleus, leading to chemical variability in S. curtisii and S. aphylla.


Assuntos
Alcaloides/química , Alcaloides/isolamento & purificação , Stemonaceae/química , Stemonaceae/genética , Alcaloides/farmacologia , Estrutura Molecular , Especificidade da Espécie , Tailândia
13.
Drug Test Anal ; 3(6): 337-44, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21698778

RESUMO

Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history.


Assuntos
Química Farmacêutica/história , Descoberta de Drogas/história , Alcaloides/análise , Alcaloides/história , Alcaloides/isolamento & purificação , Analgésicos/síntese química , Analgésicos/história , Analgésicos/uso terapêutico , Antipiréticos/síntese química , Antipiréticos/história , Antipiréticos/uso terapêutico , Aspirina/síntese química , Aspirina/história , Aspirina/uso terapêutico , Barbitúricos/síntese química , Barbitúricos/história , Barbitúricos/uso terapêutico , Química Orgânica/história , Hidrato de Cloral/síntese química , Hidrato de Cloral/história , Hidrato de Cloral/uso terapêutico , Clorofórmio/síntese química , Clorofórmio/história , Clorofórmio/uso terapêutico , Indústria Farmacêutica/história , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , Humanos , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/história , Farmacologia/história , Preparações de Plantas/química , Preparações de Plantas/história , Preparações de Plantas/isolamento & purificação , Preparações de Plantas/uso terapêutico , Toxicologia/história
14.
Planta Med ; 77(4): 368-73, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20862641

RESUMO

A new norditerpene alkaloid, 10-hydroxy-8- O-methyltalatizamine (1), was isolated from the whole plant of ACONITUM ANTHORA L. besides the known isotalatizidine (2) and hetisinone (3). The structures were determined by means of HR-ESI-MS, 1D and 2D NMR spectroscopy, including ¹H-¹H COSY, NOESY, HSQC and HMBC experiments, resulting in complete ¹H and ¹³C chemical shift assignments for 1- 3, and revision of some earlier ¹³C-NMR data. The effects of the isolated compounds, together with twenty-one other ACONITUM alkaloids with different skeletal types and substitution patterns, on hERG channels were studied by the whole-cell patch clamp technique, using the QPatch-16 automated patch clamp system. At 10 µM, aconitine, 14-benzoylaconine 8- O-palmitate, songoramine, gigactonine and neolinine demonstrated significant hERG K+ channel inhibition; all other compounds exerted only low (6-21%) inhibitory activity.


Assuntos
Aconitum/química , Alcaloides/farmacologia , Diterpenos/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Extratos Vegetais/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Alcaloides/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas , Bloqueadores dos Canais de Potássio/isolamento & purificação
15.
Zhong Yao Cai ; 32(7): 1128-31, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19873742

RESUMO

OBJECTIVE: To compare the extraction yield and economic cost in the microwave-assisted extraction and conventional extraction of Corydalis yanhusuo. METHODS: Both of the extractions of Corydalis yanhusuo were optimized by orthogonal design. The contents of tetrahydropalmatine and total alkaloids were determined by HPLC and ultraviolet spectrophotometer, respectively. Meanwhile, the electricity consumption was determined in the extraction process. RESULTS: Comparing with conventional extraction, the microwave-assisted extraction saved time and money, and provided higher extraction yield of tetrahydropalmatine and total alkaloids. CONCLUSION: The microwave-assisted extraction has advantages in high efficiency and low cost.


Assuntos
Alcaloides de Berberina/isolamento & purificação , Corydalis/química , Micro-Ondas , Plantas Medicinais/química , Tecnologia Farmacêutica/métodos , Alcaloides/análise , Alcaloides/isolamento & purificação , Alcaloides de Berberina/análise , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Etanol/química , Extratos Vegetais/química , Reprodutibilidade dos Testes , Rizoma/química , Solventes/química , Tecnologia Farmacêutica/economia
16.
J Nat Prod ; 72(2): 243-7, 2009 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-19245264

RESUMO

In 2003, we reported the isolation, structure elucidation, and pharmacology of epiquinamide (1), a novel alkaloid isolated from an Ecuadoran poison frog, Epipedobates tricolor. Since then, several groups, including ours, have undertaken synthetic efforts to produce this compound, which appeared initially to be a novel, beta2-selective nicotinic acetylcholine receptor agonist. Based on prior chiral GC analysis of synthetic and natural samples, the absolute structure of this alkaloid was established as (1S,9aS)-1-acetamidoquinolizidine. We have synthesized the (1R*,9aS*)-isomer (epi-epiquinamide) using an iminium ion nitroaldol reaction as the key step. We have also synthesized ent-1 semisynthetically from (-)-lupinine. Synthetic epiquinamide is inactive at nicotinic receptors, in accord with recently published reports. We have determined that the activity initially reported is due to cross-contamination from co-occurring epibatidine in the isolated material.


Assuntos
Alcaloides , Quinolizinas , Ranidae/metabolismo , Receptores Nicotínicos/efeitos dos fármacos , Alcaloides/síntese química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Venenos de Anfíbios/síntese química , Venenos de Anfíbios/química , Venenos de Anfíbios/isolamento & purificação , Venenos de Anfíbios/toxicidade , Animais , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Quinolizinas/síntese química , Quinolizinas/química , Quinolizinas/isolamento & purificação , Quinolizinas/toxicidade , Esparteína/análogos & derivados , Esparteína/síntese química , Esparteína/química , Esparteína/economia , Estereoisomerismo
17.
Prog Mol Subcell Biol ; 42: 125-39, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16805441

RESUMO

The laboratory culture of the barnacle, Balanus amphitrite has made it possible to supply cypris larvae for antifouling assays all year round. The settlement of cyprids obtained from cultured B. amphitrite was indistinguishable from cyprids reared from field-collected barnacles. In laboratory cyprid settlement assays of extracts from marine sessile organisms, antifouling activity was expressed as the 99% inhibitory concentration (IC99), and toxicity as the 30% lethal concentration (LC30). The lipophilic extract of the marine bryozoan, Zoobotryon pellucidum, which showed promising antifouling activity, yielded 2,5,6-tribromo-1-methylgramine (TBG) by bioassay-guided isolation. The inhibitory activity of TBG was 6 times as strong as that of bis-(n-butyltin)oxide (TBTO), while its toxicity to cypris larvae was one-tenth that of TBTO. A structure-activity relationship study with 155 indole derivatives led to the discovery of the non-toxic antifoulant candidates 5,6-dichlorogramine, 5-chloro-2-methylgramine, and 5,6-dichrolo-1-methylgramine (DCMG), the latter being selected as the antifouling paint ingredient for performance evaluation tests (panel tests) following the results of a preliminary safety tests. A silicone-based antifouling paint containing 5-10% of DCMG was prepared and tested in the field; the painted surfaces remained almost barnacle-free for 1.5 years similar to silicone coatings such as Biox. Since the leaching rate of DCMG from the paint surface could be controlled by the addition of an acrylic acid-styrene copolymer (ASP), the life of the antifouling performance is expected to be improved. Thus, an extremely non-toxic silicone-based antifouling paint containing DCMG is under development.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Alcaloides/isolamento & purificação , Animais , Antiparasitários/isolamento & purificação , Briozoários/metabolismo , Avaliação Pré-Clínica de Medicamentos , Larva/efeitos dos fármacos , Biologia Marinha , Pintura , Gestão de Riscos , Relação Estrutura-Atividade , Thoracica/efeitos dos fármacos , Compostos de Trialquitina/farmacologia
18.
Planta Med ; 67(2): 150-2, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11301862

RESUMO

Callus cultures were initiated from stem parts of Nothapodytes foetida on Murashige and Skoog's medium supplemented with different growth regulators. Suspension cultures were established and the cell biomass was higher in the presence of NAA in comparison with 2,4-D. Culture medium supplemented with NAA (10.74 microM) and BA (2.22 microM) attained 31.3 g/l DW during 20 days of cultivation in shake flasks. In the presence of NAA, maximum concentrations of camptothecin (0.035 mg/ml) and 9-methoxycamptothecin (0.026 mg/ml) were found in the medium. Alkaloid production was reduced in presence of 2,4-D in the culture medium. Cells contained trace amount of alkaloids. Alkaloids were detected and identified by means of TLC and HPLC.


Assuntos
Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Camptotecina/análogos & derivados , Camptotecina/isolamento & purificação , Plantas Medicinais/química , Camptotecina/economia , Camptotecina/provisão & distribuição , Células Cultivadas , Estrutura Molecular , Caules de Planta/química
19.
Yan Ke Xue Bao ; 12(2): 83-7, 1996 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-9639853

RESUMO

PURPOSE: MTT assay was evaluated on cytoxicity for suspension growing cell lines of SO-Rb50 and SO-Rb70, and the toxicity of TAH (the total alkaloid of peqanum harmala L) on the above cell lines was assessed. METHODS: The relationships between cell number and optical density, between optical density and exposure time of MTT, and the stability of formazan crystal solution in MDSO were determined. And the toxicity of TAH on the cell lines of SO-Rb50 and SO-Rb70 in vitro with MTT assay was assessed. RESULTS: There was a direct proportional relationship between the amount of cell number and its optical density; The optical density increased gradully within 12 hours of the MTT incubation time; The stable time of the formazan crystal solved in DMSO was 11 hours. The IC50 values (micrograms/ml) of TAH on SO-Rb50 were 10.66, 4.82 respectively for 48 and 72 hours; and on SO-Rb70 were 6.38, 4.2 respectively for 48 and 72 hours. CONCLUSION: MTT assay can be used for suspension growing cell lines of SO-Rb50 and SO-Rb70: TAH has obvious toxicity to these two cell lines.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Plantas Medicinais/química , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Alcaloides/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Células Tumorais Cultivadas/efeitos dos fármacos
20.
Ann Pharm Fr ; 49(5): 244-8, 1991.
Artigo em Francês | MEDLINE | ID: mdl-1841524

RESUMO

The importance of alkaloids and heterosides extracted from plants is clearly established. A specialised industry makes them available to drug companies by means of technological processes which now make a wide range of extractions possible. Due to the large investments in equipment and raw materials, the procedures and processes must be optimised so that each extraction corresponds to a specific procedure dictated by a large number of parameters. Competitivity is only obtained at this cost. The raw material is the major limitation: because of the variability of drugs and because of economic factors which include the risk of falsifications. The large sums of money invested mean that a greater financial support, from outside of the company, will probably be necessary in the future, which is likely to fragilise the company.


Assuntos
Alcaloides/isolamento & purificação , Indústria Química/tendências , Indústria Farmacêutica , Indústria Química/economia , França
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