RESUMEN
Three steroidal saponins, including astrogorgiosides A (1) and B (2) bearing acetamido-glucose moieties, and astrogorgioside C (3) with a 19-nor and bearing an aromatized B ring steroid aglycone, together with a known major saponin dimorphoside A (4), were obtained from the gorgonian Astrogorgia dumbea collected near Dongshan Island in East China Sea. Structures of these compounds were elucidated by in-depth spectral and chemical methods, including 2D-NMR, HR-ESI-MS spectra, and acidic hydrolysis. For the first time, acetamido-glucose moiety is being reported from a gorgonian. The B-ring aromatized steroid aglycone of compound 3 is also rare in marine natural products. Compounds 1-3 exhibited moderate cytotoxic activity with IC50 values of 26.8-45.6 µM against human tumor cells Bel-7402 and K562.
Asunto(s)
Escarabajos/química , Saponinas/aislamiento & purificación , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , China , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Saponinas/química , Saponinas/farmacologíaRESUMEN
Preclinical in vivo assessment of the pharmacologic activity of nonpeptidyl thrombopoietin receptor (TPOR) agonists is very difficult because of the high species specificity of such agonists. In this study, we have developed a novel and simple in vivo hollow-fiber assay to preclinically evaluate TPOR agonists. The 32D-mpl cell line was generated by stable transfection of human TPOR into 32D lymphoblast cells and shown to be a specific model for nonpeptide TPOR agonists in vitro. Stably transfected 32D-mpl cells were then sealed in hollow fibers and implanted into nude mice. Cells in hollow fibers specifically responded to TPOR agonists, including thrombopoietin and eltrombopag, a nonpeptide small-molecule TPOR agonist, but not to granulocyte colony-stimulating factor or erythropoietin. Oral administration of eltrombopag stimulated 32D-mpl cell proliferation, prevented 32D-mpl cell apoptosis, and stimulated the phosphorylation of cellular signaling transducers and activators of transcription in a TPOR- and dose-dependent manner. These results indicate that the hollow-fiber assay is a specific and efficient model for rapidly evaluating the in vivo activity of small-molecule TPOR agonists.
Asunto(s)
Evaluación Preclínica de Medicamentos/instrumentación , Receptores de Trombopoyetina/agonistas , Animales , Benzoatos/farmacología , Línea Celular/trasplante , Ensayo de Unidades Formadoras de Colonias , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Eritropoyetina/farmacología , Femenino , Factor Estimulante de Colonias de Granulocitos/farmacología , Humanos , Hidrazinas/farmacología , Implantes Experimentales , Interleucina-3/farmacología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Pirazoles/farmacología , Proteínas Recombinantes de Fusión/agonistas , Proteínas Recombinantes/farmacología , Factor de Transcripción STAT3/metabolismo , Trombopoyetina/farmacología , TransfecciónRESUMEN
Three new 18-oxygenated ent-kaurane diterpenoids, isoleuconins A-C (1-3) and ten known diterpenoids were isolated from the aerial parts of Isodon leucophyllus. The structures were elucidated by 1D and 2D NMR spectroscopic analysis. All of the compounds were evaluated for their cytotoxicity. Rabdokunmin A (13) showed significant cytotoxicity against HT-29 cells, with an IC50 value of 6.2 microM.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos de Tipo Kaurano/aislamiento & purificación , Isodon/química , Línea Celular Tumoral , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Humanos , Relación Estructura-ActividadRESUMEN
Ten new highly oxygenated triterpenoids, kadcoccilactones A-J (1-10), and two known triterpenoids, kadsuphilactone A and micrandilactone B, were isolated from the stems of the evergreen climbing plant Kadsura coccinea. The structures of the new compounds were elucidated by spectroscopic evidence, with that of 1 confirmed by single-crystal X-ray diffraction analysis. This is the first report on nortriterpenoids (2, 4-6, 8-10) from the genus Kadsura.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Kadsura/química , Plantas Medicinales/química , Triterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Humanos , Conformación Molecular , Estructura Molecular , Tallos de la Planta/química , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
Four new triterpenoids, kadlongilactones C-F (2-5), containing a consecutive hexacyclic [7,7,5,6,6,6] ring system, were isolated from the leaves and stems of Kadsura longipedunculata. In comparison with the NMR data of kadlongilactones A (1) and D (3), a significant phenomena was discovered that ring D of 3 inverted from a half-chair in 1 to a half-boat conformation when the HO-16 group changed from alpha- to beta-orientation. The structures of 2-5 were established on the basis of detailed spectroscopic analysis, and DFT computational methods were applied in the structural validation of compounds 3 and 5. Compounds 1-4 showed significant cytotoxicity against A549, HT-29, and K562 cell lines with IC50 values of 0.49-3.61 microM in vitro.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Kadsura/química , Plantas Medicinales/química , Triterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Tallos de la Planta/química , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
Three biogenetically interesting ent-kaurane-derived metabolites, alboatisins A-C (1-3), featuring a C-13-oxygenated ent-atisane skeleton, have been isolated from the aerial parts of Isodon albopilosus. Their structures were determined on the basis of spectroscopic evidence. Compound 2 exhibited cytotoxicity against A549 and HT-29 human cancer cells, with IC50 values of 8.3 and 7.9 microM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Isodon/química , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Humanos , Concentración 50 Inhibidora , Estructura MolecularRESUMEN
Four new withanolides, physagulins L-O (1-4), were isolated from the MeOH extract of the aerial parts of Physalis angulata L. (Solanaceae), together with seven known withanolides, compounds 5-11. Their structures were determined by spectroscopic techniques, including 1H-, 13C-NMR (DEPT), and 2D-NMR (HMBC, HMQC, 1H,1H-COSY, NOESY) experiments, as well as by HR-MS. All eleven compounds were tested for their antiproliferative activities towards human colorectal-carcinoma (HCT-116) and human non-small-cell lung-cancer (NCI-H460) cells. Compound 5 exhibited the highest anticancer activity against the HCT-116 cell line, with an IC50 value of 1.64+/-0.06 microM. Compound 9 exhibited the highest cytotoxicity towards the NCI-H460 cell line, with an IC50 value of 0.43+/-0.02 microM.
Asunto(s)
Citotoxinas/aislamiento & purificación , Physalis , Componentes Aéreos de las Plantas , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Citotoxinas/química , Humanos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , WithaniaRESUMEN
ent-Abietane diterpenoids, hebeiabinins A-F (1-5), together with seven known diterpenoids were isolated from leaves of Isodon rubescens var. rubescens. The structures of 1-5 were established on the basis of spectroscopic analyses, including application of 2D NMR spectroscopic techniques. The diterpenoids isolated were evaluated for the cytotoxicity against A549, HT-29, and K562 tumor cells. Compound 5 was the most active with IC(50) value of 0.91 microM against A549 cells.
Asunto(s)
Abietanos/química , Supervivencia Celular/efectos de los fármacos , Isodon/química , Hojas de la Planta/química , Abietanos/aislamiento & purificación , Abietanos/toxicidad , Antineoplásicos/toxicidad , Línea Celular Tumoral/efectos de los fármacos , Humanos , Isodon/toxicidad , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
Three new ent-kaurane diterpenoids, parvifoline Z (1), parvifoline AA (2), and parvifoline AB (3), together with 14 known compounds, were isolated from the leaves of Isodon parvifolius. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopy and mass spectrometry, and by comparison with known compounds. These three new diterpenoids included three types of ent-kauranoids, namely, C(20)-non-oxygenated-ent-kauranoid, 7,20-cyclo-ent-kauranoid and 6,7-seco-ent-kauranoid-7,20-olide. Compounds 1 and 2 exhibited significant cytotoxicities against A549, HT-29, and K562 cell lines.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon/química , Plantas Medicinales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Relación Estructura-ActividadRESUMEN
From the dried roots of Euphorbia fischeriana, seven new diterpenoids, 3alpha,17-dihydroxy-ent-pimara-8(14),15-diene (1), 7beta,11beta,12beta-trihydroxy-ent-abieta-8(14),13(15)-dien-16,12-olide (2), 17-acetoxyjolkinolide B (3), 13beta-hydroxy-ent-abiet-8(14)-en-7-one (4), 12-deoxyphorbaldehyde-13-acetate (5) 12-deoxyphorbaldehyde-13-hexadecacetate (6), and 12-deoxyphorbol-13-(9Z)-octadecanoate-20-acetate (7), and two known compounds, 12-deoxyphorbol-13-decanoate (8) and prostratin (9), were isolated. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The structure of compound 1 was confirmed by single-crystal X-ray crystallography. Compounds 3 and 8 exhibited potent cytotoxic activity to Ramos B cells with IC50 values of 0.023 and 0.0051 microg/mL, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Euphorbia/química , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Linfoma de Burkitt , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Humanos , Estructura Molecular , Raíces de Plantas/química , Células Tumorales CultivadasRESUMEN
Nine new 7alpha,20-epoxy- ENT-kaurane diterpenoids, parvifolines O - W (1 - 9), together with five known analogues, lasiocarpanin (10), rosthorin A (11), longikaurin E (12), adenolin D (13) and longikaurin B (14), were isolated from the leaves of Isodon parvifolius. Their structures were determined by means of spectroscopic analysis. Selected diterpenoids (1 - 10) were tested for their antiproliferative activity against A549, HT-29 and K562 cells. Compounds 3, 7, 8 and 10 showed moderate inhibitory activity against all three cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Isodon , Fitoterapia , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/administración & dosificación , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/uso terapéutico , Humanos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la PlantaRESUMEN
Nine new 7alpha,20-epoxy-ent-kaurane diterpenoids, parvifolines C-K (1-9), together with 12 known analogues, rabdoternin G (10), adenolin E (11), lasiodonin (12), lushanrubescensin F (13), parvifoliside (14), effusanin A (15), effusanin B (16), effusanin E (17), taibaihenryiin A (18), shikokianin (19), maoyecrystal J (20), and the acetonide of lasiodonin (21), were isolated from the leaves of Isodon parvifolius. The structures of compounds 1-9 were determined on the basis of spectroscopic methods including extensive 1D and 2D NMR analysis. The new diterpenoids (1-9) and lasiodonin (12) were evaluated for their inhibitory activity against A549, HT-29, and K562 cell lines.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Medicamentos Herbarios Chinos , Isodon/química , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Células Tumorales CultivadasRESUMEN
[reaction: see text] A phytochemical study of the secondary metabolites produced by the species of Isodon rubescens has led to the isolation of three new dimeric ent-kauranoids and two known ones. The most important of these compounds are bisrubescensin A (1), which contains an unprecedented C(23) ent-kaurane unit, and bisrubescensin C (3), which is the precursor of bisrubescensin B (2) from the viewpoint of biosynthesis. Their structures were determined on the basis of extensive spectroscopic analysis and chemical evidence.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon/química , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Células Tumorales CultivadasRESUMEN
AIM: To investigate the apoptosis-inducing effect of cheliensisin A (GC-51), a novel styryl-lactone isolated from Goniothalamus cheliensis, on human promyelocytic leukemia HL-60 cells and the mechanism of action involved. METHODS: Apoptotic cell death was determined by morphological examination and DNA agarose gel electrophoresis. The activity of caspase-3 was assessed using Western blotting and the expression of Bcl-2 and Bax genes was analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: GC-51 significantly inhibited the proliferation of HL-60 cells with an IC50 of 2.4+/-0.2 micromol/L and effectively induced apoptosis in HL-60 cells. Exposure of HL-60 cells to 10 micromol/L GC-51 for 8 h resulted in approximately 53% of the cells undergoing apoptosis. Caspase-3 was activated in GC-51-treated cells, which was manifested by the appearance of the 17 kDa active form of caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP). Meanwhile, GC-51 markedly reduced the expression of the anti-apoptotic gene Bcl-2 and increased the expression of the pro-apoptotic gene Bax. The apoptosis-inducing effect of GC-51 was cAMP-dependent protein kinase (PKA) dependent because PKA, but not the protein kinase C, specific inhibitor H-89, blocked the induction of apoptosis by GC-51 in HL-60 cells. CONCLUSION: The results demonstrate that GC-51 effectively induces apoptosis in HL-60 cells and that this effect is PKA-dependent and involves the downregulation of Bcl-2 expression and the activation of caspase-3.
Asunto(s)
Annonaceae , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Compuestos Epoxi/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Pironas/farmacología , Annonaceae/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Caspasa 3 , Caspasas/metabolismo , Proliferación Celular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Compuestos Epoxi/química , Compuestos Epoxi/aislamiento & purificación , Regulación Neoplásica de la Expresión Génica , Células HL-60 , Humanos , Isoquinolinas/farmacología , Plantas Medicinales/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Pironas/química , Pironas/aislamiento & purificación , Sulfonamidas/farmacología , Proteína X Asociada a bcl-2RESUMEN
Ten new sesquiterpenoids, namely, eupachinilides A-J (1-10), together with seven known sesquiterpenoids, eupachifolin D (11), budlein B (12), 8 beta-(4'-hydroxytiglyloxy)-2 beta-hydroxy-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-3,10(14),11(13)-trien-6,12-olide (13), 1,10-hydrobahia (14), 2 alpha-hydroxyeupatolide (15), eupaserrin (16), and mollisorin B (17), were isolated from the whole plant of Eupatorium chinense. Their structures were elucidated mainly by spectral methods, especially 2D NMR techniques. Eupachinilides A (1), E (5), F (6), and I (9) exhibited moderate cytotoxic activities against several tumor cell lines. The structures assigned previously for eupachifolins B (11a), C (13a), and D (11) were revised by spectral analysis and 2D NMR techniques.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Eupatorium/química , Plantas Medicinales/química , Sesquiterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Medicina Tradicional China , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos/farmacología , EstereoisomerismoRESUMEN
A new cyclopeptide, grifficyclocin A (1), and a new aporphine alkaloid, griffinin (2) were isolated together with two known styryllactones from the stems of Goniothalamus griffithii. Their structures were identified spectroscopically and chemically. Among them, the griffinin (2) was isolated as the enol form in two tautomers, and the two known styryllactones, goniothalamin (3) and 8- O-acetylgoniotriol (4), showed selective in vitro antitumor activities.