RESUMO
A phytochemical investigation on Euphorbia alatavica Boiss resulted in the isolation of nine compounds, including two new ones, alatavolide and alatavoic acid (1-2). Chemical structures of these compounds were established on the basis of 1D, 2D NMR, and HR-MS techniques, and by comparison with data reported in the literature. Compounds 1, 2, 4, 6, 8, and 9 were screened for cytotoxicity using the MTT assay. Among these compounds, the new compound 2 showed moderate cytotoxicity against Hela, MCF-7 and A549 cell lines (IC50 values of 16.4 ± 3.2, 14.5 ± 2.8, 22.3 ± 3.1 µM, respectively), while the known compound 8 exhibited the most potent cytotoxicity with the IC50 values of 6.5 ± 3.1, 1.9 ± 0.9, 8.6 ± 3.5 µM, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Euphorbia/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células HeLa , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos/química , Triterpenos/farmacologiaRESUMO
One new compound alatavinol (1), together with five known compounds, kaempferol (2), quercetin (3), laricircsinol (4), secoisolariciresinol (5) and loliolide (6) were isolated from the whole plant of Euphorbia alatavica Boiss. Those compounds were isolated and purified by various column chromatographic methods and their structures were elucidated by spectroscopic (1D, 2D NMR, and HR-MS) chemical analyses. All compounds were isolated for the first time from E. alatavica Boiss, and biochemical pathway of the new compound has been hypothesized. Furthermore, these compounds were evaluated for antioxidant properties based on the DPPH radical scavenging activities. Results showed that IC50 values of compounds 1, 3, 4, 5 and 6 were 25.69, 1.88, 2.87, 11.55 and 17.81 µg/mL, respectively, as compared to the control ascorbic acid (5.34 µg/mL).
Assuntos
Antioxidantes/isolamento & purificação , Euphorbia/química , Sequestradores de Radicais Livres/isolamento & purificação , Extratos Vegetais/química , Antioxidantes/química , Compostos de Bifenilo , Sequestradores de Radicais Livres/química , Estrutura Molecular , Picratos , Relação Estrutura-Atividade , TriterpenosRESUMO
Three new isopimarane diterpenes and one new nor-triterpenes, along with five known diterpenes were isolated from the whole areal part of Ephorbia alatavica Boiss. The structures of the new compounds (1-4) were determined based on extensive spectroscopic analysis, including HR-ESIMS, 1D and 2D NMR data. A plausible biosynthetic pathway for new compounds (1-4) were hypothesized. All isolated compounds were screen for cytotoxicity activity against MCF-8, HeLa and A549 cell lines in vitro by MTT assay. New compound 1 and known 9 showed potential cytotoxic activities with IC50 values of 15.327⯵g/mL, 23.066⯵g/mL against MCF-8 cell lines, compound1 showed noteworthy cytotoxic activity with IC50 13.033⯵g/mL against A549 cancer cell line. New compounds 2, 4 and 4 showed moderate cytotoxic activities three human cancer lines with IC50 value around 50⯵g/mL, which compared with positive control doxorubicin (DOX).
Assuntos
Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Euphorbia/química , Triterpenos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Estrutura MolecularRESUMO
Five new (1-5) and ten known (6-15) jatrophane diterpenoids were isolated from the fructus of Euphorbia sororia and their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1 and 4 were confirmed by X-ray crystallographic analysis. Cytotoxicity and anti-multidrug resistance effects of these jatrophane diterpenoids were evaluated in multidrug-resistant MCF-7/ADR breast cancer cells with an overexpression of P-glycoprotein (P-gp). Eight compounds (1, 2, 4, 6, 8, 10, 11, and 15) showed promising chemoreversal abilities compared to verapamil (VRP). The most potent compound, Euphosorophane A (1), possessed many advantages, including (1) high potency (EC50â¯=â¯92.68⯱â¯18.28â¯nM) in reversing P-gp-mediated resistance to doxorubicin (DOX), low cytotoxicity, and a high therapeutic index, (2) potency in reversing resistance to other cytotoxic agents associated with MDR, and (3) inhibition of P-gp-mediated Rhodamine123 (Rh123) efflux function in MCF-7/ADR cells. The results of the Western blot analysis indicated that the multidrug resistance (MDR) reversal induced by 1 was not due to the inhibiton of P-gp expression. Compound 1 stimulated P-gp-ATPase activity and caused the dose-dependent inhibition of DOX transport activity. Lineweaver-Burk and Dixon plots implied that 1 was a competitive inhibitor to DOX in the binding site of P-gp with a Ki of 0.49-0.50⯵M. Our data suggested that 1 had a high binding affinity toward the DOX recognition site of P-gp. This resulted in inhibiting DOX transport, increasing intracellular DOX concentration, and finally resensitizing MCF-7/ADR to DOX. In addition, we discussed some added contents in the structure-activity relationship (SAR) of jatrophane diterpenoids.