RESUMO
Forty-three quinolizidine alkaloids (1-43), including twelve new matrine-type ones, sophalodes A-L (1-7, 17, 19 and 28-30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1-4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction analysis, and quantum chemical calculation. In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30⯵M, respectively. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, additional research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27⯵M.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Simulação de Acoplamento Molecular , Quinolizidinas/farmacologia , Sophora/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Quinolizidinas/química , Quinolizidinas/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
Five new quinolizidine alkaloids were isolated from the leaves of Cylicomorpha solmstii (Urb.) Urb. (Caricaceae) and named cylicomorphins A-E (1-5). They all are ester derivatives of the same basic quinolizidine skeleton bearing hydroxy, methyl, and ethanoic acid substituents. Their structures were mainly established by NMR spectroscopy, and the absolute configuration is proposed on the basis of VCD data and Mosher ester derivatization. Compound 5 displayed cytotoxicity in the 10 µM range against an HCT-116 cell line.
Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Caricaceae/química , Quinolizidinas/farmacologia , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Camarões , Células HCT116 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Quinolizidinas/isolamento & purificaçãoRESUMO
The objective of this work is to elucidate the fate of quinolizidine alkaloids (QA) during the lupin protein extraction process assisted with ultrasound and the evaluation of the nutritional and functional properties of the protein fraction. Proximal characterization, concentration of anti-nutritional compounds, amino acid profile and protein solubility profile of flours from three lupin species were (L. albus, L. angustifolius and L. mutabilis) assessed. The result showed a significant difference (p < 0.05) in protein concentration, fat, total alkaloids and particle size between the three species flours. Based on these parameters, the most different Lupinus species (L. mutabilis and L. angustifolius) were chosen to study the behavior of the protein fraction in terms of functionality, composition and resistance to thermal treatments. The results obtained for L. mutabilis described the ultrasound effect as beneficial for protein yield (14% more than control), QA reduction from bagasse (81% less than control) and protein isolate production (50% less than control). On the other hand, L. angustifolius was more resistant to the ultrasound effect with no significant difference between treatments (10 and 15 min) and control but with the lower toxicity and better amino acid score. These results will be useful to design processes to assist in the objective of meeting the future protein demand of the population.
Assuntos
Lupinus/química , Lupinus/metabolismo , Quinolizidinas/isolamento & purificação , Alcaloides/química , Alcaloides/isolamento & purificação , Aminoácidos/análise , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteínas/isolamento & purificação , Proteínas/metabolismo , Quinolizidinas/química , Sementes/metabolismo , Ondas UltrassônicasRESUMO
Two new quinolizidine-based alkaloids (2 and 12), along with ten known ones (1, 3-11) were isolated from the roots of S. tonkinensis. Their structures were determined by spectroscopic data (including NMR, MS, IR, and UV), X-ray single crystal diffraction, electronic circular dichroism analyses (ECD), and comparing with related literatures. Compounds 1, 3-12 at non-toxic concentrations exhibited potent anti-inflammatory activities according to in vitro and in vivo anti-inflammatory tests. Among them, (-)-anagyrine (4), sophocarpine (8), 14ß-hydroxymatrine (10), and 7ß-sophoramine (12) showed more potent in vitro anti-inflammatory activities, and 5α,14ß-dihydroxymatrine (2), (-)-anagyrine (4), sophocarpine (8), and 5α-hydroxymatrine (9) exhibited better in vivo anti-inflammatory effects.
Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Quinolizidinas/farmacologia , Sophora/química , Alcaloides/isolamento & purificação , Animais , Animais Geneticamente Modificados , Anti-Inflamatórios/isolamento & purificação , Azocinas , China , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Quinolizidinas/isolamento & purificação , Quinolizinas , Células RAW 264.7 , Peixe-ZebraRESUMO
Quinolizidine alkaloids, a main form of alkaloids found in the genus Sophora, have been shown to have many pharmacological effects. This review aims to summarize the photochemical reports and biological activities of quinolizidine alkaloids in Sophora. The collected information suggested that a total of 99 quinolizidine alkaloids were isolated and detected from different parts of Sophora plants, represented by lupinine-type, cytisine-type, sparteine-type, and matrine-type. However, quality control needs to be monitored because it could provide basic information for the reasonable and efficient use of quinolizidine alkaloids as medicines and raw materials. The nonmedicinal parts may be promising to be used as a source of quinolizidine alkaloid raw materials and to reduce the waste of resources and environmental pollution. In addition, the diversity of chemical compounds based on the alkaloid scaffold to make a biological compound library needs to be extended, which may reduce toxicity and find new bioactivities of quinolizidine alkaloids. The bioactivities most reported are in the fields of antitumor activity along with the effects on the cardiovascular system. However, those studies rely on theoretical research, and novel drugs based on quinolizidine alkaloids are expected.
Assuntos
Alcaloides/farmacologia , Extratos Vegetais/farmacologia , Quinolizidinas/farmacologia , Sophora/química , Alcaloides/isolamento & purificação , Alcaloides/normas , Alcaloides/uso terapêutico , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antimetabólitos/isolamento & purificação , Antimetabólitos/farmacologia , Antimetabólitos/uso terapêutico , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/normas , Antineoplásicos/uso terapêutico , Fármacos Cardiovasculares/isolamento & purificação , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Desenvolvimento de Medicamentos , Descoberta de Drogas , Humanos , Inseticidas , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/normas , Extratos Vegetais/uso terapêutico , Controle de Qualidade , Quinolizidinas/isolamento & purificação , Quinolizidinas/normas , Quinolizidinas/uso terapêuticoRESUMO
A new stereoisomer Meso-araguspongine C together with nine reported macrocyclic bis-quinolizidine alkaloids araguspongines A, C, E, L, N-P, petrosin, and petrosin A were isolated from marine sponge Xestospongia muta. Stereochemistry of meso-araguspongine C (2) and araguspongines N-P (3-5) were established by their NMR data and conformational analyses. Both araguspongine C (1) and meso-araguspongine C (2) exhibited great cytotoxic activity towards HepG-2, HL-60, LU-1, MCF-7, and SK-Mel-2 human cancer cells (IC50 in the range of 0.43-1.02 µM). At a concentration of 20 µM, isolated compounds (1-10) also showed modest inhibitory effects (from 7.6 to 40.8%) on the NO production in LPS activated RAW264.7 macrophages.
Assuntos
Alcaloides/isolamento & purificação , Quinolizidinas/isolamento & purificação , Quinolizinas/isolamento & purificação , Xestospongia/química , Alcaloides/química , Animais , Linhagem Celular Tumoral , Humanos , Lipopolissacarídeos , Compostos Macrocíclicos/isolamento & purificação , Camundongos , Conformação Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7RESUMO
Twelve quinolizidine alkaloids were isolated from Sophora tonkinensis by means of silica gel, preparative MPLC, and preparative HPLC. On analysis of NMR spectroscopic data, their structures were established as 3-(4-hydroxyphenyl)-4-(3-methoxy-4-hydroxyphenyl)-3,4-dehydroquinolizidine(1), lanatine A(2), cermizines C(3), senepodines G(4), senepodines H(5), jussiaeiines A(6), jussiaeiines B(7),(+)-5α-hydroxyoxysophocarpine(8),(-)-12ß-hydroxyoxysophocarpine(9),(-)-clathrotropine(10),(-)-cytisine(11), and (-)-N-methylcytisine(12), respectively. Compounds 1-7 were first isolated from Sophora L. plant. In the in vitro assays,the isolated compounds 1, 3, 6-10 exhibited potent activity against CVB3 with IC50 of 6.40, 3.25, 4.66, 3.21, 0.12, 0.23 and 1.60, and with selective index values(SI=TC50/IC50)of 12.0, 5.6, 13.0, 15.1, 50.1, 26.2, and 23.6, respectively. Compounds 1, 3, and 7 exhibited activity against staphylococcus aureus(ATCC 29213)with MICvalues of 8.0, 3.5, 6.0 gâ¢L⻹, respectively. Compounds 1, 3, 7, and 12 exhibited activity against staphylococcus aureus(ATCC 33591)with MIC values of 18.0, 7.5, 8.0, 12.0 gâ¢L⻹, respectively. Compounds 2, 6, 7 exhibited activity against Escherichia coli(ATCC 25922) with MIC values of 1.0, 3.2, 0.8 gâ¢L⻹.
Assuntos
Alcaloides/isolamento & purificação , Quinolizidinas/isolamento & purificação , Sophora/química , Antibacterianos/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Quinolizinas , Staphylococcus aureus/efeitos dos fármacosRESUMO
Rhizopus oligosporus has proven beneficial in the detoxification of lupin seeds. The fermentation process is mainly affected by the initial pH in the medium. In the range of growth of mold, there are maximum enzymatic activities in pH of 3.5 and 5.5. Metabolism change occurs at these pH levels; therefore, we studied the growth, pH changes, dry matter intake, and alkaloid degradation within 48 h of fermentation. Cultures of lupin agar (LA) with pH of 3.5 and 5.5 were made in Petri dishes with lupin flour. Results showed pH directly affects the degradation of alkaloids and fungal growth. Detoxification levels achieved were 16.58 and 63.23 % in treatments LA 3.5 and LA 5.5, respectively. Fungal growth was 0.919 mg/cm(2) in LA 3.5 and 1.081 mg/cm(2) in LA 5.5. Maximum degradation rate in LA 5.5 was given between 16 and 20 h, which coincided with maximum fungal growth. Despite having similar dry matter intake in both treatments, a pH of 3.5 did not show the same degree of detoxification. The analysis with exponential, yield of growth, yield of dry matter intake and luedeking and piret equations, confirm the relation between intake and growth with detoxification. Dry matter intake equation predicts with R (2) of 0.94 the detoxification in LA 5.5. A pH of 5.5 is directly related with detoxification and fungal development.
Assuntos
Alcaloides/metabolismo , Lupinus/química , Quinolizidinas/metabolismo , Rhizopus/metabolismo , Alcaloides/isolamento & purificação , Biotransformação , Meios de Cultura/química , Concentração de Íons de Hidrogênio , Quinolizidinas/isolamento & purificação , Rhizopus/crescimento & desenvolvimento , Sementes/química , Fatores de TempoRESUMO
INTRODUCTION: Many species in the Lupinus genus are poorly defined morphologically, potentially resulting in improper taxonomic identification. Lupine species may contain quinolizidine and/or piperidine alkaloids that can be acutely toxic and/or teratogenic, the latter resulting in crooked calf disease. OBJECTIVE: To identify characteristic alkaloid profiles of Lupinus sabinianus, L. garfieldensis and L. sericeus which would aid in discriminating these species from each other and from L. sulphureus. METHODS AND MATERIALS: Quinolizidine and piperidine alkaloids were extracted from herbarium specimens and recent field collections of L. sabinianus, L. garfieldensis and L. sericeus. The alkaloid composition of each species was defined using GC-FID and GC-MS and compared using multivariate statistics. RESULTS: Each of the three species investigated contained a diagnostic chemical fingerprint composed of quinolizidine and/or piperidine alkaloids. CONCLUSION: The alkaloid profiles of Lupinus sabinianus, L. garfieldensis and L. sericeus can be used as a tool to discriminate these species from each other and L. sulphureus as long as one considers locality of the collection in the case of L. sabinianus.
Assuntos
Alcaloides/análise , Cromatografia Gasosa/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lupinus/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Bovinos , Lupinus/classificação , Estrutura Molecular , Piperidinas/análise , Piperidinas/química , Piperidinas/isolamento & purificação , Quinolizidinas/análise , Quinolizidinas/química , Quinolizidinas/isolamento & purificação , Reprodutibilidade dos Testes , Especificidade da EspécieRESUMO
Lycopodium alkaloids have attracted the attention of many natural product chemists and synthetic organic chemists due to their important biological activities and unique skeletal characteristics. In this review we describe isolation and asymmetric syntheses of several new alkaloids such as lycoposerramines-C, -V, -W, and cernuine, and show that asymmetric total synthesis played a key role in elucidating the structures of these complex natural products.
Assuntos
Alcaloides/síntese química , Produtos Biológicos/síntese química , Produtos Biológicos/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Lycopodium/química , Modelos Químicos , Alcaloides/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Estrutura Molecular , Piperidinas/síntese química , Piperidinas/isolamento & purificação , Quinolinas/síntese química , Quinolinas/isolamento & purificação , Quinolizidinas/síntese química , Quinolizidinas/isolamento & purificação , EstereoisomerismoRESUMO
Four new biphenyl and biphenyl ether quinolizidine N-oxide alkaloids, 5- EPI-dihydrolyfoline N-oxide (1), decamine N-oxide (2), lagerstroemine N-oxide (3), and lagerine N-oxide (4), were isolated from the aerial parts of Lagerstroemia indica, and their structures were established by extensive spectroscopic studies. In addition, the inhibitory effects of isolated compounds on rat lens aldose reductase (RLAR) were examined.
Assuntos
Alcaloides/química , Compostos de Bifenilo/química , Óxidos N-Cíclicos/química , Lagerstroemia/química , Quinolizidinas/química , Aldeído Redutase/efeitos dos fármacos , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Compostos de Bifenilo/isolamento & purificação , Compostos de Bifenilo/farmacologia , Fracionamento Químico , Óxidos N-Cíclicos/isolamento & purificação , Óxidos N-Cíclicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Éteres/química , Espectroscopia de Ressonância Magnética , Componentes Aéreos da Planta/química , Quinolizidinas/isolamento & purificação , Quinolizidinas/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Although the quinolizidine alkaloids and flavonoids, the main active components of the traditional Chinese medicine Sophora flavescens, have been largely investigated, a new matrine alkaloid derivative 9alpha-hydroxy-7,11-dehydromatrine (1) and a rare 1,4-diazaindan-type alkaloid flavascensine (17), together with 15 known alkaloids, were isolated from S. flavescens. The structures were established on the basis of spectroscopic techniques.
Assuntos
Alcaloides/isolamento & purificação , Quinolizidinas/isolamento & purificação , Sophora/química , Alcaloides/química , Medicamentos de Ervas Chinesas/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Estrutura Molecular , Plantas Medicinais/química , Quinolizidinas/químicaRESUMO
Two new biphenylquinolizidine alkaloids, 5-epi-dihydrolyfoline (1) and its stereoisomer, dihydrolyfoline (2), along with lagerine (3) were isolated from the aerial parts of Lagerstroemia indica. The structures of compounds 1-3 were elucidated by extensive spectroscopic techniques.
Assuntos
Alcaloides/isolamento & purificação , Lagerstroemia/química , Quinolizidinas/isolamento & purificação , Alcaloides/química , Coreia (Geográfico) , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Quinolizidinas/química , EstereoisomerismoRESUMO
Calia secundiflora (Ortega) Yakovlev (Fabaceae) is considered a medicinal plant in Mexico but has scarcely been used because of the toxicity of its quinolizidine alkaloids. Several quinolizidine alkaloids have shown bactericidal, nematicidal, and fungicidal activities. The purpose of this study was to identify the alkaloids in the seeds and evaluate the activity of the organic extract on several phytopathogenic fungi and bacteria. An in vitro bioassay was conducted with species of the following phytopathogenic fungi: Alternaria solani, Fusarium oxysporum and Monilia fructicola; and of the following bacteria Pseudomonas sp., Xanthomonas campestris and Erwinia carotovora. Cytisine, lupinine, anagyrine, sparteine, N-methylcytisine, 5,6-dehydrolupanine, and lupanine were identified by liquid chromatography-mass spectrometry in the extract of seeds; the most abundant compound of the extract was cytisine. It was observed that the crude extract of Calia secundiflora was moderately active on bacteria and more potent on phytopathogenic fungi. In contrast cytisine showed the opposite effects.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Fabaceae/química , Extratos Vegetais/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alternaria/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Azocinas/farmacologia , Candida/efeitos dos fármacos , Cromatografia Líquida , Fusarium/efeitos dos fármacos , Espectrometria de Massas , Pectobacterium carotovorum/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Pseudomonas/efeitos dos fármacos , Quinolizidinas/isolamento & purificação , Quinolizidinas/farmacologia , Quinolizinas/farmacologia , Sementes/química , Esparteína/farmacologia , Xanthomonas campestris/efeitos dos fármacosRESUMO
Alkaloid profiles in skin of poison frogs/toads (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae) are highly dependent on diet and hence on the nature of habitat. Extracts of the two species of toads (Melanophryniscus klappenbachi and Melanophryniscus cupreuscapularis) from similar habitats in the Corrientes/Chaco Provinces of Argentina have similar profiles of alkaloids, which differ considerably in profiles from other Melanophryniscus species from Brazil, Uruguay and Argentina. Structures of two major alkaloids 239Q (1) and 275I (2) were determined by mass, FTIR, and NMR spectral analysis as 5Z,9Z-3-(1-hydroxybutyl)-5-propylindolizidine and 6Z,10E-4,6-di(pent-4-enyl) quinolizidine, respectively. A third alkaloid, 249F (3), is postulated to be a homopumiliotoxin with an unprecedented conjugated exocyclic diene moiety.
Assuntos
Bufonidae/metabolismo , Indolizidinas/química , Quinolizidinas/química , Pele/química , Alcaloides/análise , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Argentina , Cromatografia Gasosa-Espectrometria de Massas , Conteúdo Gastrointestinal/química , Indolizidinas/análise , Indolizidinas/isolamento & purificação , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Quinolizidinas/análise , Quinolizidinas/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Four new Daphniphyllum alkaloids, daphnioldhanines H-K ( 1- 4), along with 34 known alkaloids, were isolated from Daphniphyllum oldhami. The known alkaloid dehydrodaphnigraciline ( 5) is now reported as a natural product. Their structures were elucidated by spectroscopic methods, especially 2D NMR techniques. The effects against platelet aggregation of compounds 1, 3, and 5 were evaluated, and 3 showed stronger activity against platelet aggregation induced by PAF. This is the first report of quinolizidine alkaloids from the genus Daphniphyllum.
Assuntos
Alcaloides/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Plantas Medicinais/química , Inibidores da Agregação Plaquetária/isolamento & purificação , Quinolizidinas/isolamento & purificação , Saxifragaceae/química , Alcaloides/química , Alcaloides/farmacologia , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Quinolizidinas/química , Quinolizidinas/farmacologiaRESUMO
A new matrine-type alkaloid, 7α-hydroxysophoramine (1), was isolated from the aerial parts of Sophora alopecuroides together with eight known alkaloids, 12ß-hydroxysophocarpine (2), sophoramine (3), 14ß-hydroxymatrine, matrine, sophoridine, sophocarpine, adenocarpine, and baptifoline. The structures of compounds 1-3 were confirmed through single-crystal X-ray diffraction analysis.