RESUMO
Plasiatine (1), isolated from the seeds of Plantago asiatica, is an unprecedented indole analogue linked to a phenylpropanoid moiety via a carbon bond that builds up a novel heteromeric construction with a C19N2 scaffold. Its structure was determined by spectroscopic data and computational evidence. Notably, experimental assay demonstrated that 1 significantly enhanced the activity of the nonreceptor protein tyrosine phosphatase Shp2 in vitro in a concentration-dependent manner with an EC50 value of 0.97 µM, and activated phosphorylation of ERK, a known target of Shp2. Moreover, plasiatine (1) promoted hepatocellular HepG2 cells migration. Molecular docking suggested that plasiatine (1) binds to the catalytic cleft of Shp2. These results identified plasiatine (1) as the first small molecule Shp2 activator, and it warrants further investigation as a novel pharmaceutical tool to study the function of Shp2 in tumorigenesis.
Assuntos
Produtos Biológicos/farmacologia , Ativadores de Enzimas/farmacologia , Indóis/farmacologia , Extratos Vegetais/farmacologia , Plantago/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Produtos Biológicos/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Ativadores de Enzimas/isolamento & purificação , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Humanos , Indóis/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosforilação , Extratos Vegetais/isolamento & purificação , Ligação Proteica , Processamento de Proteína Pós-Traducional , Sementes/química , Análise EspectralRESUMO
Lancolide E (1) featuring a complex tetracyclo[5.4.0.0(2,4).0(3,7)]undecane-bridged system that is constructed by an eight-, a three-, and two five-membered carbon rings in a sterically congested region was obtained in trace amounts from a "talented" schinortriterpenoid producer Schisandra lancifolia. Its structure was fully characterized by combining 2D NMR spectroscopy, theoretical calculations, and X-ray diffraction analysis. The biogenetic pathway of 1 was proposed to involve a Prins cyclization.
Assuntos
Medicamentos de Ervas Chinesas/síntese química , Plantas Medicinais/química , Schisandra/química , Triterpenos/síntese química , Alcanos , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos/químicaRESUMO
Three unreported sesquiterpenes possessing two new skeletons, tabasesquiterpenes A-C (1-3), together with three known sesquiterpenes (3-6) were isolated from the leaves of Nicotiana tabacum. Their structures were determined mainly by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compounds 1-6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 2 exhibited high anti-TMV activity with inhibition rate of 35.2%, which were higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activity with inhibition rates in the range of 20.5-28.6%.
Assuntos
Antivirais/química , Nicotiana/química , Folhas de Planta/química , Sesquiterpenos/química , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Antivirais/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
Aspergillines A-E (1-5) are highly oxygenated cyclopiazonic acid (CPA)-derived alkaloids bearing a rigid and sterically congested hexacyclic indole-tetrahydrofuran-tetramate scaffold, isolated from the endophytic fungus Aspergillus vesicolor. Apergillines A-C represent a new subclass of CPA-derived alkaloids, and aspergillines B and E possess a butanoic acid methyl ester moiety. The structures, including absolute configuration, were elucidated by interpretation of the NMR, X-ray crystallographic, and circular dichroism data. All compounds displayed anti-TMV and cytotoxic activities.
Assuntos
Alcaloides/isolamento & purificação , Antineoplásicos/isolamento & purificação , Aspergillus/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Indóis/química , Pirrolidinonas/química , Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Dicroísmo Circular , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Five new biphenyls, tababiphenyls A-E (1-5), together with five known ones (5-10), were isolated from the leaves of Nicotiana tabacum, of which compound 1 possessed a seldom reported 6-carbons unit in biphenyls. Their structures were established on the basis of extensive spectroscopic analyses. All compounds were tested for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 3 and 5 exhibited high anti-TMV activities with inhibition rate of 48.4% and 32.1%, respectively, which were higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activities with inhibition rates in the range of 18.6-28.7%, respectively.
Assuntos
Antivirais/química , Compostos de Bifenilo/química , Nicotiana/química , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Antivirais/farmacologia , Compostos de Bifenilo/farmacologia , Estrutura Molecular , Doenças das Plantas/virologia , Folhas de Planta/químicaRESUMO
Six unique nortriterpenoids, lancifonins A-F (1-6), were isolated from Schisandra lancifolia. Their absolute configurations were determined by X-ray diffraction and ECD calculation. The conformational analysis of 1 was performed due to the unanticipated changes of Cotton effects in its ECD spectrum. Compounds 5 and 6 possess a unique 7/7 fused carbocyclic core with an internal ester bridge between C-9 and C-14, and 5 exhibited protective activity against H2O2-induced oxidative damage on Caco-2 cells.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Schisandra/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Fármacos Anti-HIV/química , Antioxidantes/química , Células CACO-2 , Cristalografia por Raios X , Humanos , Peróxido de Hidrogênio/farmacologia , Conformação Molecular , Estrutura Molecular , Folhas de Planta/química , Triterpenos/químicaRESUMO
Two new triterpenoids, schisphendilactone A and B (1 and 2), together with three known triterpenoids, were isolated from the stems of Schisandra sphenanthera. Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 2 showed moderate inhibitory activity against SW480 cancer cell line, and compound 5 exhibited promising anti-HIV-1 activity with EC50 value of 0.52 µg ml(-1) and therapeutic index value of 117.12.
Assuntos
Fármacos Anti-HIV , Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Schisandra/química , Triterpenos , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Efeito Citopatogênico Viral , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Caules de Planta/química , Estereoisomerismo , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Three new dibenzocyclooctadiene lignans, marlignans M-O (1-3), together two known ones, were isolated from the leaves and stems of Schisandra wilsoniana. The structures of 1-3 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 2 showed anti-HIV-1 activity with an EC50 value of 5.82 microg/mL and a therapeutic index (TI) of more than 12.8. Compound 3 showed obvious bioactivity in inhibiting Epstein-Barr virus early antigen (EBV-EA) activation.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , HIV-1/efeitos dos fármacos , Lignanas/isolamento & purificação , Schisandra/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antígenos Virais/metabolismo , Lignanas/química , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Folhas de Planta/química , Caules de Planta/químicaRESUMO
Six new lignans, schisphenlignans F-K (1-6), together with ten known ones, were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR, MS and CD spectra. In addition, some compounds were tested for their acute activity on insulin sensitivity in 3T3-L1 differentiated adipocytes and anti-HIV-1 activity.
Assuntos
Lignanas/isolamento & purificação , Extratos Vegetais/química , Schisandra/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , HIV-1/efeitos dos fármacos , Lignanas/farmacologia , Camundongos , Estrutura Molecular , Extratos Vegetais/farmacologia , Folhas de Planta/química , Caules de Planta/químicaRESUMO
Three new phenolic compounds, yunnanensins A-C (1-3), together with fourteen known ones (4-17), were isolated from the leaves and stems of Parakmeria yunnanensis. The structures of new compounds were established on the basis of extensive spectroscopic analyses. Several compounds showed weak anti-HIV-1 activity.
Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Magnoliaceae/química , Fenóis/farmacologia , Fármacos Anti-HIV/isolamento & purificação , Células Cultivadas , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Folhas de Planta/química , Caules de Planta/químicaRESUMO
Five new dibenzocyclooctadiene lignans, schisphenlignans A-E (1-5), together with eight known ones, were isolated from the stems of Schisandra sphenanthera. The structures of 1-5 were elucidated based on the analysis of their NMR, MS and circular dichroism (CD) spectra. Some isolates were tested for their acute activities on insulin sensitivity in 3T3-L1 differentiated adipocytes, but none of them showed significant bioactivity with 10 µM administration of the tested compounds.
Assuntos
Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Lignanas/química , Lignanas/farmacologia , Caules de Planta/química , Schisandra/química , Células 3T3-L1 , Animais , Ciclo-Octanos/isolamento & purificação , Insulina/metabolismo , Resistência à Insulina , Lignanas/isolamento & purificação , CamundongosRESUMO
Four new compounds, maninsigins A-D (1-4), including two new neolignans (1-2) and two new sesquiterpenes (3-4), as well as ten known compounds (5-14), were isolated from the leaves and stems of Manglietia insignis. Their structures were established on the basis of extensive spectroscopic analyses. In addition, some compounds were tested for their cytotoxic and neurite outgrowth-promoting activities, as well as their antagonistic activity toward FXR ligand.
Assuntos
Magnoliaceae/química , Fenóis/farmacologia , Terpenos/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Modelos Moleculares , Neurônios/efeitos dos fármacos , Fenóis/química , Folhas de Planta/química , Caules de Planta/química , Ratos , Terpenos/químicaRESUMO
A pair of new triterpenoid epimers, kadcoccitones A (1) and B (2), together with a new biogenetically related compound kadcoccitone C (3), were isolated from Kadsura coccinea. The epimers featured an unprecedented carbon skeleton with a 6/6/5/5-fused tetracyclic ring system unit and a C(9) side chain. Their structures were determined by spectroscopic data, ECD calculation, and single-crystal X-ray diffraction. Compounds 1 and 3 showed anti-HIV-1 activity with an EC(50) value of 47.91 and 32.66 µg/mL, respectively.
Assuntos
Fármacos Anti-HIV/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Kadsura/química , Triterpenos/isolamento & purificação , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , HIV-1/efeitos dos fármacos , Estrutura Molecular , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Ten new triterpenoids, schiglausins A-J (1-10), as well as four known compounds, were isolated from the stems of Schisandra glaucescens. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR spectra and CD experiment. Compound 8 was determined to be a norlanostane triterpenoid. The crystal structure of compound 1 has been determined using single-crystal X-ray analysis while its absolute configuration was assigned on the basis of the CD spectrum. All isolates were tested for their FXR agonistic and antagonistic effects.
Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Schisandra/química , Triterpenos/química , Triterpenos/isolamento & purificação , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Estrutura Molecular , Caules de Planta/química , Triterpenos/farmacologiaRESUMO
Neolaxiflorin A (1), an unprecedented ent-kaurane diterpenoid with a bicyclo[3.1.0]hexane unit, and its seco-derivative, neolaxiflorin B (2), along with two known compounds 3 and 4 were isolated from the leaves of Isodon eriocalyx var. laxiflora. The absolute configuration of 1 was determined by spectral methods and single crystal X-ray diffraction analysis. Compound 4 and the synthesized compound 5 exhibited significant cytotoxicity.
Assuntos
Compostos Bicíclicos com Pontes/química , Cicloexanos/química , Diterpenos do Tipo Caurano/química , Isodon/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos do Tipo Caurano/farmacologia , Humanos , Modelos Moleculares , Conformação MolecularRESUMO
This study investigated the 70% aqueous acetone extract of the fruits of Schisandra rubriflora which led to the isolation of eight lignans, including a new isolate, rubrisandrin C (1), and seven known lignans (2-8). The structure of 1 was established by extensive 1D and 2D NMR spectroscopy and its absolute stereochemistry was determined by CD spectrum. Compounds 1-5 and 7-8 were evaluated for their anti-HIV-1 activity that showed inhibitory activity on HIV-1(IIIB) induced syncytium formation with EC(50) values in the range of 2.26 approximately 20.4 microg/mL. Compounds 1 and 7 exerted their obvious protection of HIV-1(IIIB) inducted MT-4 host cells lytic effects with a selectivity index of 15.4 and 24.6, respectively.