RESUMO
The family Trimusculidae produce labdane diterpenes, which differ in the degree and type of esterification with acetoxy and isovaleroyl ester, predominantly. In this article, we describe the isolation from the marine pulmonate Trimusculus peruvianus, collected on intertidal rocks of Chilean coasts, of two new labdane diterpenes closely related to the above mentioned characteristics. Their structures were determined by spectroscopic data and correspond to 6beta-hydroxy-labda-8, 13-dien-15-ol and 3, 19-isovaleroyl-6beta, 9alpha-dihydroxylabda-Delta(8,17), 13-dien-15-oic acid.
Assuntos
Diterpenos/química , Diterpenos/isolamento & purificação , Moluscos/química , Animais , Chile , Esterificação , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Three new tetrahydrofuran derivatives, marine monoterpenes, with an unusual chlorobromo vinyl functional group, have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and molecular mechanics (MM2) calculations. These compounds are related to pantofuranoids isolated from the antarctic Pantoneura plocamioides, which strongly suggests a close relationship between these species.
Assuntos
Furanos/isolamento & purificação , Hidrocarbonetos Halogenados/isolamento & purificação , Monoterpenos , Rodófitas/química , Terpenos/isolamento & purificação , Chile , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Furanos/química , Furanos/farmacologia , Hidrocarbonetos Halogenados/química , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo , Terpenos/química , Terpenos/farmacologiaRESUMO
Four new marine monoterpenes have been isolated from two species of marine red algae, Plocamium cartilagineum and Pantoneura plocamioides. The structures and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence and suggest a relationship between P. cartilagineum and P. plocamioides.
RESUMO
We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 microM decreased cell growth by 14%, while at 45 microM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.
Assuntos
Divisão Celular/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Neoplasias da Próstata/patologia , Quinonas/farmacologia , Citometria de Fluxo , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Proteínas dos Microtúbulos/isolamento & purificação , Microtúbulos/metabolismo , Invasividade Neoplásica , Ativadores de Plasminogênio/antagonistas & inibidores , Ativadores de Plasminogênio/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Alga Marinha , Células Tumorais CultivadasRESUMO
Six new polyoxygenated marine monoterpenes have been isolated from the Antarctic alga Pantoneura plocamioides. The structure and relative stereochemistry of these compounds, denominated pantopyranoids A-C (1-3), and pantoisofuranoids A-C (4-6) were determined on basis of spectroscopic evidence.