RESUMO
Two new quinone derivatives, epoxyquinophomopsins A (1) and B (2), were purified from the EtOAc extract of endophytic fungus Phomopsis sp isolated from Morus cathayana. The structures of both compounds were determined based on 1D and 2D NMR and mass spectral data, as well as by x-ray diffraction analysis for 1. Compounds 1 and 2 were screened against eight receptor- (RTKs) and eight non-receptor tyrosine kinases (nRTKs). Both compounds showed strong inhibitory properties against Bruton's Tyrosine Kinase (nRTK) with their kinase activity were 19% and 20%, respectively. Only compound 1 that showed strong inhibitory properties against RTKs EGFR and HER-4 with its kinase activity were 16 and 15%, respectively. Thus, both compounds have potential as tyrosine kinase inhibitors.
Assuntos
Phomopsis/química , Proteínas Tirosina Quinases/efeitos dos fármacos , Estrutura MolecularRESUMO
Amyloid ß (Aß) aggregation plays an essential role in promoting the progression of Alzheimer's disease (AD). Therefore, the inhibition of Aß aggregation is a potential therapeutic approach for AD. Herein, twenty-seven biflavonoids with different inter-flavonyl linkages and methoxy substitution patterns were isolated from several plants, and their Aß40 aggregation inhibitory activity was evaluated by the thioflavin-T fluorescence assay. Amentoflavone (1) and its monomethoxy derivatives (2, 3, and 5) exhibited the most potent inhibitory activity, with IC50 values of approximately 5⯵M. It was clarified that increasing the number of methoxy substituents on the biflavonoid structures attenuated the inhibitory activity. Moreover, the linkage and the methoxy substitution pattern had a marked influence on the inhibitory activity. Our investigation strongly supports that biflavonoids can be considered a new type of anti-Alzheimer agents that may be successfully developed for AD patients.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Biflavonoides/química , Doença de Alzheimer/patologia , HumanosRESUMO
A new farnesylated flavonol (4'-O-methylmacagigantin) and a new geranylated stilbene (macatrichocarpin H), together with eight known phenolic compounds, have been isolated from the leaves of Macaranga trichocarpa. Structures of these compounds were determined based on NMR and mass spectrroscopic data. Cytotoxic properties of the isolated compounds were tested against P-388 cells showing that mactrichocarpin G was the most active compound with IC50 was 3.5µM.
Assuntos
Euphorbiaceae/química , Flavonóis/química , Estilbenos/química , Animais , Linhagem Celular Tumoral , Flavonóis/isolamento & purificação , Indonésia , Camundongos , Estrutura Molecular , Folhas de Planta/química , Estilbenos/isolamento & purificaçãoRESUMO
A major hallmark of Alzheimer's disease is the cerebral accumulation and resulting cytotoxicity of amyloid-ß peptides, particularly Aß42. In this study, we used an MTT assay to investigate the inhibitory activity of biflavonoids 1-22 against Aß42 cytotoxicity in PC-12 cell cultures. Cytoprotective effects were observed for the following amentoflavone type biflavonoids: podocarpusflavone B 8, isoginkgetin 10, sciadopitysin 13, and kayaflavone 15. These biflavonoids exhibited strong activity in tested compounds, with EC50 values of 5.18, 10.77, 9.84, and 5.29 µM, respectively. Cell viability tests of PC-12 cells revealed that biflavonoids 13 and 15 had stronger inhibitory activities than apigenin 23 and (-)-epigallocatechin gallate 24.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Biflavonoides/química , Biflavonoides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Animais , Células PC12 , Ratos , Relação Estrutura-AtividadeRESUMO
Two new dihydroflavonol derivatives, macarecurvatins A and B, have been isolated from the leaves of Macaranga recurvata (Euphorbiaceaae), along with the known compounds diisoprenylaromadendrin, glyasperin A and broussoflavonol F. The structures of the new compounds were determined on the basis of spectroscopic evidence. Upon cytotoxic evaluation against P-388 cells, macarecurvatin B showed strong activity with an IC50 of 0.83 microM.
Assuntos
Euphorbiaceae/química , Flavonóis/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Leucemia P388/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Camundongos , Folhas de Planta/química , Espectrofotometria UltravioletaRESUMO
Two geranylated and methylated flavonol derivatives, macarhizinoidins A (1) and B (2), along with a known phenolic compound methyl 4-isoprenyloxycinnamate (3), have been isolated from the methanol extract of the leaves M. rhizinoides. The structures of these compounds were identified based on their spectroscopic data. On cytotoxic evaluation against murine leukemia P-388 cells, compounds 1-2 showed IC50 values of 11.4 and 13.9 microM, respectively, while compound 3 was inactive.
Assuntos
Euphorbiaceae/química , Flavonóis/isolamento & purificação , Animais , Flavonóis/química , Flavonóis/farmacologia , Leucemia P388/tratamento farmacológico , Leucemia P388/patologia , Camundongos , Extratos Vegetais/análiseRESUMO
Here, we describe amentoflavone-type biflavonoids, which were isolated from natural sources and were found to inhibit beta-secretase (BACE-1). The structure-activity relationship was studied, and compounds 1-8, 10, 17, and 18 showed BACE-1 inhibitory activity. Among these compounds, 2,3-dihydroamentoflavone 17 and 2,3-dihydro-6-methylginkgetin 18 exhibited potent inhibitory effects with IC(50) values of 0.75 and 0.35 microM, respectively.
Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Biflavonoides/química , Inibidores de Proteases/química , Secretases da Proteína Precursora do Amiloide/metabolismo , Biflavonoides/farmacologia , Inibidores de Proteases/farmacologia , Relação Estrutura-AtividadeRESUMO
Two chalcone derivatives, 2'-hydroxychalcone (1) and desmethylinfectocaryone (2), together with five known phenolic compounds infectocaryone (3), cryptocaryone (4), kurzichalcolactone A (5), pinocembrin (6) and trans-N-feruloyltyramine (7), were isolated from the methanol extract of the wood of Cryptocarya konishii. The structures of the new compounds were determined based on the analysis of spectroscopic data, including UV, IR, 1D and 2D NMR, and mass spectra. Evaluation of the cytotoxic and tyrosine kinase inhibitory activities of compounds 1-7 showed that compounds 2-4 strongly inhibited the growth of murine leukemia P-388 cells, whereas compound 4 significantly inhibited the enzyme.
Assuntos
Cryptocarya , Citotoxinas/toxicidade , Fenóis/toxicidade , Extratos Vegetais/toxicidade , Inibidores de Proteínas Quinases/toxicidade , Proteínas Tirosina Quinases/antagonistas & inibidores , Citotoxinas/química , Citotoxinas/isolamento & purificação , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Humanos , Fenóis/química , Fenóis/isolamento & purificação , Casca de Planta , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Proteínas Tirosina Quinases/metabolismoRESUMO
New prenylated flavones, artoindonesianins Z-4 and Z-5, together with four known prenylated flavones, artonin E, 12-hydroxyartonin E, artobiloxanthone, and cycloartobiloxanthone, have been isolated from the methanol extract of the tree bark of Artocarpus lanceifolius. The structures of these compounds were determined on the basis of spectroscopic data, including UV, IR, 1D and 2D NMR, and mass spectra. The cytotoxic effect of the isolated compounds against murine leukemia P-388 cells is described.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Artocarpus/química , Flavonas/química , Flavonas/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Flavonas/isolamento & purificação , Leucemia P388/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Metanol , Camundongos , Casca de Planta/química , Prenilação , Solventes , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
A new 2-arylbenzofuran derivative (diptoindonesin G) (1), along with nine known oligostilbenes, have been isolated and identified from the acetone extract of the tree bark of Hopea mengarawan. The structures of these compounds were determined based on spectroscopic data, including 2D NMR and HREIMS spectra. On cytotoxic evaluation of the isolated compounds against murin leukemia P-388 cells, compound 1 was the strongest in inhibiting the growth of the cells.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Dipterocarpaceae/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Benzofuranos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia P388/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Camundongos , Casca de Planta/química , Solventes , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Two isoprenylated flavanones, macatrichocarpins A and B, and two isoprenylated dihydrochalcones, macatrichocarpins C and D, have been isolated and identified from the acetone extract of the leaves of Macaranga trichocarpa. The structures of these compounds were determined based on spectroscopic data, including UV, IR, 1D and 2D NMR spectroscopic and HREIMS data. This is the first report of the presence of dihydrochalcone derivatives in the genus Macaranga.
Assuntos
Chalconas/química , Euphorbiaceae/química , Flavonas/química , Estrutura MolecularRESUMO
A new oligostilbenoid, diptoindonesin C, has been isolated from the tree bark of Shorea pinanga Scheff., along with the two known oligostilbenoids gnetin H and hopeaphenol, and a known coumarin scopoletin. The new oligostilbenoid was moderately active against brine shrimps Artemia salina.
Assuntos
Dipterocarpaceae/química , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Estilbenos/isolamento & purificação , Estrutura Molecular , Fenóis , Estilbenos/análise , Estilbenos/químicaRESUMO
A new oxepinoflavone, artoindonesianin E1 (1), was isolated from the wood of Artocarpus elasticus, along with four known prenylated flavones: artocarpin (2), cycloartocarpin (3), cudraflavones A (4) and C (5). The structure of the new compound was identified by spectroscopic methods. Upon cytotoxic evaluation against murine leukemia P-388 cells, the new compound showed IC(50) 5.0 microg/mL.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artocarpus/química , Flavonas/farmacologia , Flavonoides/farmacologia , Oxepinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flavonas/química , Flavonas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Oxepinas/química , Oxepinas/isolamento & purificaçãoRESUMO
A new farnesylated flavonol derivative, macagigantin (1), together with two known flavonoids, glyasperin A (2) and apigenin (3), had been isolated from the acetone extract of the leaves of Macaranga gigantea. The structure of the new compound was elucidated as 6-farnesylkaempferol based on its spectroscopic data, including UV, IR, 1D and 2D NMR, and HR-EI-MS spectra. Compounds 1-3 were evaluated for their cytotoxic properties against P-388 cells, their IC(50) values being 11.3, 6.0, and 5.1 microM, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Euphorbiaceae/química , Flavonóis/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Flavonóis/química , Flavonóis/farmacologia , Indonésia , Leucemia P388 , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Relação Estrutura-AtividadeRESUMO
A new methylated flavonol, 5,7,2',4'-tetrahydroxy-3-methoxyflavone (1), had been isolated from the methanol extract of the wood of Morus australis, along with nine known compounds, kuwanon C (2), morusin (3), morachalcone A (4), oxyresveratrol (5), 4'-(2-methyl-2-buten-4-yl)oxyresveratrol (6), moracins M (7) and C (8), alboctalol (9), and macrourin B (10). The structures of these compounds were determined based on spectral evidence, including UV, IR, NMR, and mass spectra. Cytotoxic properties of compounds 1-10 were evaluated against murine leukemia P-388 cells. The prenylated stilbene 6 and 2-arylbenzofuran 8, and morusin (3) were found to have strong cytotoxic effects with IC50 values of 6.9, 8.7, and 10.1 microM, respectively.
Assuntos
Flavonóis/química , Morus/química , Fenóis/química , Madeira , Flavonas/química , Flavonas/isolamento & purificação , Flavonóis/isolamento & purificação , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , EspectrofotometriaRESUMO
A new oligostilbenoid derivative, diptoindonesin F (1), along with five known oligostilbenoids, (-)-ampelopsin A (2), (-)-alpha-viniferin (3), ampelopsin E (4), (-)-vaticanol B (5), and (-)-hemsleyanol D (6), were isolated from the methanol extract of the tree bark of Shorea gibbosa. The structure of the new compound was determined based on the analysis of spectroscopic data, including UV, IR, NMR 1-D and 2-D, and mass spectra. Cytotoxic properties of the isolated oligostilbenoids were evaluated against murine leukemia P-388 cells with the result that compounds 2 and 4 showed the highest cytotoxicity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Dipterocarpaceae/química , Estilbenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia P388 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Estilbenos/química , Estilbenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
A new resveratrol tetramer, named diptoindonesin E, was isolated from the acetone extract of the tree bark of Dipterocarpus hasseltii, together with five known resveratrol oligomers (-)-epsilon-viniferin, laevifonol, (-)-alpha-viniferin, vaticanol B, (-)-hopeaphenol, and a coumarin, scopoletin. The structures of these compounds were determined from spectroscopic evidence. Cytotoxicity test of the isolated compounds showed that hopeaphenol strongly inhibited murine leukemia P-388 cells.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ericales , Fitoterapia , Extratos Vegetais/farmacologia , Estilbenos/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Camundongos , Casca de Planta , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/química , Estilbenos/uso terapêutico , Relação Estrutura-AtividadeRESUMO
A new flavanone, 7-hydroxy-5,6-dimethoxyflavanone (1), together with three other flavonoids, didymocarpin (2), 2',4'-dihydroxy-5',6'-dimethoxychalcone (3), and isodidymocarpin (4), had been isolated from the methanol extract of the tree bark of Cryptocarya costata. The structures of these compounds were determined based on spectral evidence, including UV, IR, 1-D and 2-D NMR, and mass spectra. Cytotoxic properties of compounds 1-4 were evaluated against murine leukemia P-388 cells. The chalcones 3 and 4 were found to have substantial cytotoxicity with IC50 of 5.7 and 11.1 microM, respectively.
Assuntos
Chalconas/isolamento & purificação , Cryptocarya/química , Flavanonas/isolamento & purificação , Caules de Planta/química , Árvores/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Chalconas/química , Chalconas/toxicidade , Flavanonas/química , Flavanonas/toxicidade , Leucemia P388 , Espectroscopia de Ressonância Magnética , Camundongos , Modelos MolecularesRESUMO
Several species of the genus Artocarpus (Moraceae) have been investigated in our laboratories during the last decade. Over 60 phenolic constituents have been discovered and characterized, including 27 new compounds from 13 Indonesian taxa of Artocarpus, namely A. champeden, A. lanceifolius, A. teysmanii, A. scortechinii, A. rotunda, A. maingayi, A. kemando, A. bracteata, A. altilis, A. fretessi, A. gomezianus, A. reticulatus and A. glaucus. The principal and the most pronounced features of these phenolic constituents are the assembly of an isoprenyl substituent at C-3 of a flavone skeleton by closure of an ether bridge or a carbon-carbon linkage with the B ring of the skeleton, which may further rearrange into xanthone to produce various classes of natural products. The structures of the new and unusual natural products are presented. Many of the metabolites also exhibit cytotoxic effect against murine leukemia P388 cells.
RESUMO
A new modified stilbene dimer, diptoindonesin D (1), was isolated from the acetone extract of the tree bark of Hopea dryobalanoides, together with seven known compounds, parviflorol (2), (-)-balanocarpol (3), heimiol A (4), hopeafuran (5), (+)-alpha-viniferin (6), vaticanol B (7) and (-)-hopeaphenol (8). Cytotoxic properties of compounds 1-8 were evaluated against murine leukemia P-388 cells. Compound 8 was found to be the most active with IC50 of 5.7 microM.