RESUMO
A novel nucleoside, 9-ß-D-ribopyranosylpurine (2), along with three known nucleosides, adenosine (1), uridine (3) and nebularine (4), were isolated from the edible mushroom, Tricholoma japonicum. The structure of 2 was determined as 9-ß-D-ribopyranosylpurine by comparing the reported spectral data of 2 with that of a synthetic compound. Isolation of the glycoside, which contains the sugar ribopyranose, from natural resources is very unusual. There are reports on the synthesis of 9-ß-D-ribopyranosylpurine (2), but this is the first report on the isolation from natural resources. The antiproliferative activity of compounds 1-4 was evaluated using human umbilical vein endothelial cells. Compound 4 showed the highest inhibitory activity.
Assuntos
N-Glicosil Hidrolases/metabolismo , Tricholoma/genéticaRESUMO
Hypoxylonol C (1), isolated from the inedible mushroom Hypoxylon truncatum, exhibited inhibitory activities against the migration and tube formation of HUVECs. A cDNA microarray analysis was performed to investigate the target of hypoxylonol C (1) in HUVECs, and it was found that the genes related to cell cycle and adhesion were down-regulated. The down-regulation of mRNA levels of cell cycle and adhesion genes was confirmed by real-time RT-PCR. Cell cycle arrest and suppression of adhesion molecule expression might be plausible mechanisms of actions for the antiangiogenic activity of hypoxylonol C (1).
Assuntos
Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Fluorenos/isolamento & purificação , Fluorenos/farmacologia , Inibidores da Angiogênese/genética , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fluorenos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Estrutura Molecular , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Eleven known prenyl xanthones, isolated from the pericarp of Garcinia mangostana, were tested for their ability to inhibit the phosphorylation of kinase domain receptor (KDR) tyrosine kinase. α-Mangostin was found to inhibit phosphorylation of KDR. α-Mangostin also showed to inhibit phosphorylation of the Y1175 residue of KDR (10 µM). This is the first report that α-mangostin inhibited the phosphorylation of KDR tyrosine kinase and also the Y1175 residue of KDR. α-Mangostin also showed inhibitory effects on proliferation of human umbilical vein endothelial cells (HUVECs) (IC(50) 1.2 µM) and human umbilical artery endothelial cells (IC(50) 2.4 µM), as well as the migration (IC(50) 0.034 µM) and tubule formation (at the concentrations of 0.6 and 1.2 µM) of HUVECs. These results suggest that the inhibition of the phosphorylation of KDR tyrosine kinase is concerned in the anti-angiogenic activity of α-mangostin.
Assuntos
Inibidores da Angiogênese/farmacologia , Xantonas/farmacologia , Inibidores da Angiogênese/química , Garcinia mangostana/química , Fosforilação/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/metabolismo , Xantonas/químicaRESUMO
Four novel benzo[j]fluoranthene derivatives, hypoxylonols C (3), D (4), E (5), and F (6), have been isolated from the mushroom Hypoxylon truncatum, together with two known benzo[j]fluoranthene derivatives, hypoxylonols A (1) and B (2). The structures were established by analysis of NMR spectroscopic data and X-ray diffraction data. Compounds 4 and 5 showed antiproliferative activity against HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical artery endothelial cells).
Assuntos
Agaricales/química , Fluorenos/isolamento & purificação , Fluorenos/química , Fluorenos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Difração de Raios XRESUMO
Three new diterpenes, myrocin D (1), libertellenone E (2), and libertellenone F (3), and a new isocoumarin, decarboxyhydroxycitrinone (4), were isolated from the marine fungus Arthrinium sacchari, together with three known compounds (5-7). The structures of 1-4 were elucidated from spectroscopic data (NMR, MS, IR), and the absolute configurations of 1-3 were determined by X-ray diffraction analysis. The antiangiogenic activity of these compounds was evaluated by measuring their antiproliferation effects on human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). Compounds 4-7 showed inhibitory activity.
Assuntos
Inibidores da Angiogênese/isolamento & purificação , Ascomicetos/química , Diterpenos/isolamento & purificação , Isocumarinas/isolamento & purificação , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Células Endoteliais/efeitos dos fármacos , Humanos , Isocumarinas/química , Isocumarinas/farmacologia , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Cordão Umbilical/citologia , Cordão Umbilical/efeitos dos fármacosRESUMO
Three novel p-terphenyl compounds, named boletopsins A (1), B (2), and C (3), and four known analogues (4-7) were isolated from fruiting bodies of the mushroom Boletopsis leucomelas. Compounds 1-7 were tested for KDR kinase inhibitory activity, and boletopsin C (3) was found to have an IC(50) value of 70.7 microM. Compound 3 also showed inhibition of proliferation of human umbilical vein endothelial cells, with an IC(50) value of 9.04 microM.
