RESUMO
Two cytotoxic constituents, namely elegaphenone and 7-epi-clusianone, were isolated from the aerial parts of Hypericum elegans Stepan ex Willd. Elegaphenone was identified as (E)-(2-(3,7-dimethylocta-2,6-dienyloxy)-4,6-dihydroxyphenyl)(phenyl)methanone by means of spectral evidence. Both compounds showed prominent cytotoxicity on HD-MY-Z, K-562 and KE-37 tumour cell lines. The IC(50) values for elegaphenone were 15.9 (HD-MY-Z), 13.9 (K-562) and 16.9 (KE-37) µmol while those of 7-epi-clusianone were 9.8 (HD-MY-Z), 11.8 (K-562) and 13.6 (KE-37) µmol. The established oligonucleosomal deoxyribonucleic acid (DNA) fragmentation of genomic DNA following short-term (6 h) or long-term (24 h) exposure to the tested compounds clearly indicates that the induction of apoptotic cell death is an important component for their cytotoxic mode of action.
Assuntos
Compostos Bicíclicos com Pontes/isolamento & purificação , Citotoxinas/isolamento & purificação , Hypericum/química , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Benzofenonas , Benzoquinonas , Compostos Bicíclicos com Pontes/análise , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Citotoxinas/análise , Citotoxinas/farmacologia , Fragmentação do DNA/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Cloreto de Metileno , Estrutura Molecular , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Fatores de TempoRESUMO
Elegaphenonoside, a new benzophenone O-rhamnoside, together with two known benzophenone O-glycosides, namely hypericophenonoside and neoannulatophenonoside, were isolated from the aerial parts of Hypericum elegans Stephan ex Willd. The structure of the new compound was established as 3',5',6-trihydroxy-4-methoxybenzophenone-2-O-alpha-L-rhamnopyranoside by means of chemical and physical evidence. In addition, the presence of kaempferol, quercetin, isoquercitrin, norathyriol, I-3,II-8-biapigenin, quercitrin, hyperoside and rutin were established in this plant.
Assuntos
Benzofenonas/química , Glicosídeos/química , Hypericum/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
A new isocoumarin, annulatomarin (1), together with the known physcion and beta-sitosterol were isolated from the aerial parts of Hypericum annulatum. The structure of the new compound was established as 6,8-dihydroxy-7-methoxy-3-phenyl-3,4-dihydro-1H-isochromen-1-one on the basis of detailed spectroscopic analysis. Annulatomarin exhibited a modest growth-inhibitory activity in vitro against human chronic myeloid leukaemia LAMA-84 cells with an IC(50) = 111 microM.
Assuntos
Hypericum/química , Isocumarinas/química , Linhagem Celular Tumoral , Emodina/análogos & derivados , Emodina/química , Humanos , Concentração Inibidora 50 , Biologia Molecular , Sitosteroides/químicaRESUMO
A new benzophenone O-glucoside neoannulatophenonoside (1) together with the known pinocembrin-7-O-glucoside were isolated from the aerial parts of Hyperium annulatum Moris (Guttiferae). The former was identified as 3',5',6-trihydroxy-4-methoxybenzophenone-2-O-beta-D-glucopyranoside by means of chemical and physical evidence. The cytoprotective effects of the new compound together with the previously isolated from this species hypericophenonoside (2), annulatophenone (3), annulatophenonoside (4), acetylannulatophenonoside (5) and 1,3,7-trihydroxyxanthone (6) were evaluated in a model of epirubicin-induced cellular toxicity in K-562 cells. While the benzophenone O-glycosides 1, 2, 4 and 5 exerted substantial cytoprotective effects against the epirubicin cytotoxicity in K-562 cells the aglycones 3 and 6 lacked any significant cytoprotective activity. Biochemical investigations aimed at evaluating the free-radical scavenging activity of the tested compounds as well as their effects on the cellular glutathione stores were carried out as well, aiming at unravelling the mechanisms of cytoprotection. Finally, the ability of 1, 4 and 5 to ameliorate epirubicin-induced anticlonogenic effects on bone marrow cells colony forming units, in vitro were also evaluated. Taken together, the experimental data indicate that the benzophenone glycosides isolated from H. annulatum have a substantial cytoprotective potential against the toxic effects induced by epirubicin and necessitates further detailed pharmacological evaluation of these compounds as possible chemoprotective/radioprotective agents.
Assuntos
Benzofenonas/farmacologia , Citoproteção/efeitos dos fármacos , Epirubicina/farmacologia , Sequestradores de Radicais Livres/farmacologia , Hypericum/química , Xantonas/farmacologia , Animais , Benzofenonas/química , Benzofenonas/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Células K562 , Camundongos , Estrutura Molecular , Células Progenitoras Mieloides/efeitos dos fármacos , Células Progenitoras Mieloides/metabolismo , Componentes Aéreos da Planta/química , Proteínas Recombinantes , Relação Estrutura-Atividade , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
Two benzophenone O-arabinosides, annulatophenonoside (1) and acetylannulatophenonoside (2) were isolated from the methanol extract of the herb of Hypericum annulatum. The structures of the benzophenones were established as 2-O-alpha-L-arabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone (1) and 2-O-alpha-L-3"-acetylarabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone (2) based on spectral and chemical evidence. A chromone, 5,7-dihydroxy-3-methylchromone (3) was isolated from the chloroform extract. Although it has been previously synthesized it is encountered in a plant source for the first time. Co-occurrence of the two new benzophenone O-arabinosides along with the biogenetically related 1,5,7-trihydroxy-3-methoxyxanthone was not found.