RESUMO
Nine new and unique xanthone derivatives, including one novel hybrid monoterpene-tetrahydroxanthone (1), three dihydro-xanthone derivatives (2-4), and five skeleton-rearranged xanthone derivatives (5-9), were obtained from a 95% EtOH extract of Garcinia oligantha leaves by a LC-MS-guided fractionation procedure. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and MS data. The relative configurations of 2 and 8 were determined via X-ray crystallographic data analysis, while the absolute configurations of 1-2, 5-9 were assigned based on a comparison of calculated and experimental ECD and/or OR data. In SRB, PI-exclusion and Hoechst staining assays, 6 showed strong cytotoxic activities which could dose-dependently induce Taxol-insensitive quiescent LNCaP cell death. Additionally, a preliminary mechanism investigation using immunoblotting and Caspase-3 activity assay, indicated that 6 induced quiescent LNCaP cell death potentially through caspase-dependent mitochondrial apoptosis pathway.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores Enzimáticos/farmacologia , Garcinia/química , Folhas de Planta/química , Xantonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
Four new dihydroxanthone derivatives (1-4), four new tetrahydroxanthone derivatives (5-8), two new xanthone derivatives (9 and 10), and two known caged tetrahydroxanthones were isolated from extracts of the leaves of Garcinia oligantha by bioassay-guided fractionation. These structures of the new compounds were elucidated by NMR and MS spectroscopic data analysis, and the absolute configurations of compounds 1 and 5-7 were determined by electronic circular dichroism and/or single-crystal X-ray diffraction analysis. Compounds 6-9 were shown to be unusual xanthone derivatives with an isopropyl group, which was confirmed by the X-ray crystallographic structure of compound 8. The inhibitory activities of these isolates against four human tumor cell lines (A549, HepG2, HT-29, and PC-3) were assayed, and compounds 1, 2, 5, 11, and 12 showed inhibitory effects on tumor cell growth, with IC50 values ranging from 2.1 to 8.6 µM.