RESUMO
Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.
Assuntos
Hypericum , Apoptose , Pontos de Checagem do Ciclo Celular , Humanos , Hypericum/química , Células MCF-7 , Estrutura Molecular , Estresse Oxidativo , Floroglucinol/químicaRESUMO
Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Hypericum/química , Floroglucinol/farmacologia , Receptor X Retinoide alfa/antagonistas & inibidores , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Floroglucinol/química , Floroglucinol/isolamento & purificação , Receptor X Retinoide alfa/metabolismo , Relação Estrutura-AtividadeRESUMO
Hyperelodiones A-C, three undescribed monoterpenoid polyprenylated acylphloroglucinols possessing 6/6/6 fused tricyclic core, were isolated from Hypericum elodeoides Choisy. Their gross structures were elucidated by HRESIMS and NMR data. The absolute configurations of hyperelodiones A-C were assigned by their calculated and compared electronic circular dichroism (ECD) spectra combined with their common biosynthetic origin. A fluorescence quenching assay suggested that hyperelodiones A-C could bind to RXRα-LBD, whereas hyperelodione C showed the strongest interaction with a KD of 12.81 µΜ. In addition, hyperelodiones A-C dose-dependently inhibited RXRα transactivation and the growth of HeLa and MCF-7 cells. Among them, hyperelodione C showed the most potent inhibitory activities and dose-dependent PARP cleavage. Molecular docking results suggested that hyperelodione C showed a different interaction mode compared with hyperelodione A and hyperelodione B. Thus, hyperelodione C can be considered as a promising lead compound for cancer therapy, which can bind to RXRα-LBD and induce HeLa and MCF-7 cell apoptosis.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Hypericum/química , Monoterpenos/farmacologia , Compostos Fitoquímicos/farmacologia , Receptor X Retinoide alfa/antagonistas & inibidores , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células MCF-7 , Conformação Molecular , Simulação de Acoplamento Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Receptor X Retinoide alfa/metabolismo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
To find small-molecule regulators of RXRα, a phytochemical study of Hypericum elodeoides was conducted. Fifteen compounds, including the new 1 and 6, were isolated from the whole plant of H. elodeoides. The absolute configuration of 1 was assigned by comparison of experimental and calculated ECD data. Compounds 1 and 6 exhibited concentration-dependent inhibitory effects on RXRα transcription and selectively inhibited the proliferation of HeLa cells. Western blot analysis suggested that 1 and 6 induced apoptosis of HeLa cells with time- and dose-dependent PARP cleavage. A caspase activation assay indicated that these two compounds triggered caspase-8 activation to induce apoptosis by the extrinsic pathway. Molecular docking results suggested that 1 and 6 interacted with the Arg319 moiety of RXRα-LBD. Ligands binding to RXRα have shown promise in the discovery of anticancer drugs. A fluorescence quenching assay indicated the binding of 1 and 6 to the RXRα with the binding constant ( KD) fitted as 68.3 and 14.0 µM, respectively. A preliminary SAR study of the isolates was conducted to enhance the knowledge of the RXRα ligands. Thus, 1 and 6 might act as the small-molecule regulators of RXRα, which target RXRα and mediate HeLa cell apoptosis through the extrinsic pathways.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Caspase 8/metabolismo , Hypericum/química , Poli(ADP-Ribose) Polimerases/metabolismo , Receptor X Retinoide alfa/antagonistas & inibidores , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Relação Estrutura-AtividadeRESUMO
Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
Assuntos
Antrodia/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Aldeído Desidrogenase/sangue , Animais , Aspartato Aminotransferases/sangue , Produtos Biológicos/química , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestenos/química , Colestenos/farmacologia , Colestenos/uso terapêutico , VLDL-Colesterol/sangue , Modelos Animais de Doenças , Etanol/toxicidade , Feminino , Carpóforos/química , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/prevenção & controle , Masculino , Malondialdeído/sangue , Camundongos , Estrutura Molecular , Triglicerídeos/sangue , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/uso terapêuticoRESUMO
Veramyosides A-J, eleven undescribed stigmastane-type steroids, including one aglycone and ten glycosides, along with three known homologues were isolated from the twigs of Vernonia amygdalina Delile (compositae). All compounds featured a stigmastane-type steroid skeleton with a unique conjugated Δ7,9(11) diene segment and highly oxygenated side chains with a γ-lactone or an α, ß-unsaturated five-membered lactone ring. The structures of veramyosides A-J and their absolute configurations were unambiguously elucidated by HR-ESI-MS, extensive NMR spectroscopy, in situ dimolybdenum CD methods, modified Mosher's method, quantum chemical calculation of their ECD curves, and CD comparison methods on basis of their biogenetic pathway. In addition, all isolates were investigated for their effects on RXRα transcription, and their effects on the NF-κB signaling pathway were also evaluated.
Assuntos
Esteroides/química , Esteroides/farmacologia , Vernonia/química , Dicroísmo Circular , Avaliação Pré-Clínica de Medicamentos/métodos , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HEK293 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Oxigênio/química , Receptor X Retinoide alfa/antagonistas & inibidores , Receptor X Retinoide alfa/genética , Esteroides/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Cytoskyrin C (1), a new bisanthraquinone with asymmetrically cytoskyrin type skeleton, together with a known symmetrical analogue (+)-epicytoskyrin (2), were isolated from an endophytic fungus ARL-09 (Diaporthe sp.). Cytoskyrin C (1) featured an asymmetrically cage-like structural motif arising from the dimerization of anthraquinone monomers by three carboncarbon bonds 9a/3', 3/9a' and 1/1'. The structure and absolute configuration of compound 1 were determined by spectroscopic analyses, ECD calculation and exciton chirality methods. Moreover, a plausible biogenetic pathway of 1-2 was predicted. Their cytotoxicities against SMMC-7721 cell as well as effects on NF-κB signaling pathway were evaluated. 2009 Elsevier Ltd. All rights reserved.
Assuntos
Antraquinonas/isolamento & purificação , Ascomicetos/química , Antraquinonas/química , Linhagem Celular Tumoral , Endófitos/química , Humanos , Estrutura Molecular , NF-kappa B/metabolismo , Orchidaceae/microbiologia , Transdução de SinaisRESUMO
Thirteen phenolic compounds were isolated from pear (Pyrus ussuriensis Maxim.) peels and leaves extracts by using various column chromatography techniques with a guided DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging assay, the result of antioxidant activity of phenolic compounds is then verified by measurement of ROS (reactive oxygen species). The isolated compounds were identified as rutin (1), (-)-catechin (2), orobol (3), daidzein (4), tricin 4'-O-[threo-ß-guaiacyl-(7â³-O-methyl)-glyceryl] ether (5), tricin 4'-O-[threo-ß-guaiacyl-(7â³-O-methyl-9â³-O-acetyl)-glyceryl] ether (6), 5,7,3',5'-tetrahydroxyflavanone (7), artselaeroside A (8), trilobatin (9), 3-(2,4,6-trihydroxyphenyl)-1-(4-hydroxyphenyl)-propan-1-one (10), quercetin-3-O-(3â³-O-galloyl)-α-l-rhamnopyranoside (11), apigenin (12) and quercetin (13) on the basis of nuclear magnetic resonance spectroscopy along with comparison with literature data. Among these compounds, quercetin and quercetin-3-O-(3â³-O-galloyl)-α-l-rhamnopyranoside exhibited potent DPPH radical-scavenging activity with IC50 (Half Maximal Inhibitory Concentration) value of 6.06 and 9.60µg/mL, respectively. The results revealed that P. ussuriensis could be used in the fields of food and medicine to prevent human aging diseases.
Assuntos
Antioxidantes/isolamento & purificação , Fenóis/isolamento & purificação , Pyrus , Compostos de Bifenilo , Frutas , Humanos , Picratos , Extratos VegetaisRESUMO
The aim of this research was to determine the chemical composition of the essential oils of Dahlia pinnata, their insecticidal activity against Sitophilus zeamais and Sitophilusoryzae and to isolate insecticidal constituents. Based on bioactivity-guided fractionation, active constituents were isolated and identified as D-limonene, 4-terpineol and α-terpineol. Essential oils and active compounds tested exhibited contact toxicity, with LD50 values ranging from 132.48 to 828.79 µg/cm(2) against S. zeamais and S. oryzae. Essential oils possessed fumigant toxicity against S. zeamais and S. oryzae with LC50 from 14.10 to 73.46 mg/L. d-Limonene (LC50 = 4.55 and 7.92 mg/L) showed stronger fumigant toxicity against target insects. 4-Terpineol (88 ± 8%) and d-limonene (87 ± 5%) showed the strongest repellency against S. zeamais and S. oryzae, respectively. The results indicate that essential oils and insecticidal constituents have potential for development into natural fumigants, insecticides or repellents for control of the stored-product insect pests.