RESUMO
Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor α (TNFα) gene expression and secretion by blocking the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-κB activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead.
Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Morus/química , NF-kappa B/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Actinas/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/química , Ciclo-Oxigenase 1/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/química , Flavonoides/química , Humanos , Macrófagos/efeitos dos fármacos , Estrutura Molecular , Raízes de Plantas/química , Tristetraprolina/efeitos dos fármacos , Tristetraprolina/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The geranylated compounds tested were compared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the antineoplastic compound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Magnoliopsida/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Flavanonas/química , Frutas/química , Humanos , Estrutura Molecular , Morus/química , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Relação Estrutura-Atividade , TurquiaRESUMO
Eight C-6-geranylflavonoids ( 1- 8) were isolated from an ethanol extract of Paulownia tomentosa fruits. Tomentodiplacone ( 1), 3'- O-methyl-5'-hydroxydiplacone ( 2), 3'- O-methyl-5'- O-methyldiplacone ( 3), and tomentodiplacone B ( 4) were obtained as new compounds, and 3'- O-methyldiplacol ( 5) was isolated for the first time from a natural source. The structures of these new compounds were determined by using mass spectrometry (including HRMS) and 1D and 2D NMR spectroscopy, and the absolute configurations of the compounds were determined by circular dichroism. The antibacterial activities of 1- 8 against seven bacteria and yeast were evaluated.
Assuntos
Antibacterianos/isolamento & purificação , Flavonoides/isolamento & purificação , Testes de Sensibilidade Microbiana , Plantas Medicinais/química , Scrophulariaceae/química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Dicroísmo Circular , República Tcheca , Flavonoides/química , Flavonoides/farmacologia , Frutas/química , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
The structure of the quaternary tetrahydroprotoberberine alkaloid escholidine is revised on the basis of 2D NMR spectroscopy and X-ray diffraction. In contrast to the originally reported constitution, escholidine bears an -OH group at C-9 and an -OCH3 group at C-10. The 1H and 13C NMR data and long-range 1H-13C and NOE interactions of escholidine are compared with those of thalifendine and tetrahydroberberrubine. The 15N NMR data of escholidine obtained by using long-range 1H-15N correlation experiments at natural abundance are also reported.