RESUMO
Six new (1, 2, 6, 8, 13, and 20) and twenty previously isolated (3-5, 7, 9-12, 14-19, and 21-26) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral Sinularia polydactyla collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds 3-7, 9-12, 14-20, and 22-26, as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids 22 and 23 showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds 11, 12, 22, and 23 at 20 µM. The results of the androgen receptor (AR) reporter assay showed that compound 11 exhibited the strongest inhibition of AR at 10 µM, while it is noteworthy that steroids 10, 16, and 20 displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds 11 and 23 showed neuroprotective activity on neuron-like SH-SY5Y cells.
Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Esteroides/farmacologia , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Oceano Índico , Células MCF-7 , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Esteroides/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
A new prenyleudesmane type diterpene, sinupol (8), and a new capnosane type diterpenoid, sinulacetate (9), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4-7 and 10). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds (8 and 9) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Diterpenos/química , Modelos Moleculares , Estrutura MolecularRESUMO
The soft coral genus Sinularia is a rich source of bioactive metabolites containing a diverse array of chemical structures. A solvent extract of Sinularia polydactyla resulted in the isolation of three new casbane diterpenes: sinularcasbane M (1), sinularcasbane N (2) and sinularcasbane O (3); in addition, known metabolites (4-5) were isolated. Compounds were elucidated on the basis of spectroscopic analyses; the absolute configuration was confirmed by X-ray analysis.
Assuntos
Antozoários/química , Diterpenos/isolamento & purificação , Animais , Cristalografia por Raios X , Diterpenos/química , Oceano Índico , Espectroscopia de Ressonância Magnética , Estrutura Molecular , SolventesRESUMO
Lobane-type diterpenoids are not frequently discovered from marine soft corals. In this paper, three new lobane type diterpenes, 13-methoxyloba-8,10,15(16),17(18)-tetraene (1), 8,10,13(15)Z,16E-lobatetraene (2) and 19-hydroxy-lobatetraene (3), and a new natural compound, 17,18-epoxyloba-16-acetoxy-8,10,13(15)-trien (4), co-occurring with a known related diterpenoid, 18-methoxyloba-8,10,13(15),16(17)-tetraene (5), were isolated from the South China Sea soft coral Sinularia polydactyla. The structures of new compounds were determined by extensive spectroscopic analysis and by comparison with those reported in the literature. In bioassay, all the isolates were inactive on antibacterial, PTP1B inhibitory, and immunological activities. This study increased the chemical diversity of marine diterpenoids.
Assuntos
Antozoários/química , Diterpenos/química , Animais , Diterpenos/isolamento & purificação , Estrutura MolecularRESUMO
Hurgadacin (1), a 24,25-bishomo-26-methylenecholesterol was isolated from the soft coral Sinularia polydactyla, collected from the Red Sea, near Hurghada at the Egyptian coast. The new steroid 1 was isolated together with the closely related polyhydroxy steroids 24-methylenecholestane-3ß,5α,6ß-triol (2) and 24-methylenecholestane-1α,3ß,5α,6ß,11α-pentol (3), in addition to the sesquiterpene lactiflorenol (4) and the trinorcarotenolide acetate peridinin (5), The structures of the isolated compounds were confirmed by intensive studies of their 1D and 2D NMR spectra and mass data. The antimicrobial and cytotoxic activities of the soft coral extract and the corresponding constituents were evaluated against diverse pathogenic microorganisms and brine shrimps, respectively.