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
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
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
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.