RESUMEN
The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-ß-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.
Asunto(s)
Cephalotaxus , Lignanos , Lignanos/análisis , Hojas de la Planta/química , Etanol , Cromatografía Líquida de Alta PresiónRESUMEN
PURPOSE: The main objective of the current study was to examine the anticancer effects of Curzerenone - a naturally occurring sesquiterpene against gemcitabine-resistant lung carcinoma cells. The effects of Curzerenone on mitochondrial-mediated apoptosis, ROS, and ERK/MAPK and NF-kB signalling pathways were also investigated in the present study. METHODS: Cell proliferation was evaluated by MTT assay. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and DAPI staining as well as flow cytometry using annexin V apoptosis assay. The effects on reactive oxygen species (ROS) as well as mitochondrial membrane potential (MMP) were examined by flow cytometry. Protein expression was examined by western blotting. RESULTS: It was found that Curzerenone induced potent antiproliferative effects against the gemcitabine-resistant lung cancer cells and exhibited an IC50 of 24 µM. The anticancer effects of curzerenone were due to the induction of apoptosis which was also associated with alteration of apoptosis-related proteins (Bax,Bcl-2). Curzerenone also caused ROS-mediated alterations in the MMP. Curzerenone induced cell death in gemcitabine-resistant lung cancer cells by activating p38 MAPK/ERK signalling pathway while NF-kB pathway was inhibited in a dose-dependent manner. CONCLUSIONS: In conclusion, the current results strongly indicate that Curzerenone may prove a potential anticancer drug candidate against drug-resistant lung cancer.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , FN-kappa B/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Terpenos/uso terapéutico , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/patología , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno , Transducción de Señal , Terpenos/farmacologíaRESUMEN
BACKGROUND: The progression of liver disease causes metabolic transformation in vivo and thus affects corresponding endogenous small molecular compounds. Metabonomics is a powerful technology which is able to assess global low-molecular-weight endogenous metabolites in a biological system. This review is intended to provide an overview of a metabonomics approach to the drug toxicology of diseases of the liver. METHODS: The regulation of, and relationship between, endogenous metabolites and diseases of the liver is discussed in detail. Furthermore, the metabolic pathways involved in drug interventions of liver diseases are reviewed. Evaluation of the protective mechanisms of traditional Chinese medicine in liver diseases using metabonomics is also reviewed. Examples of applications of metabolite profiling concerning biomarker discovery are highlighted. In addition, new developments and future prospects are described. RESULTS: Metabonomics can measure changes in metabolism relating to different stages of liver disease, so metabolic differences can provide a basis for the diagnosis, treatment and prognosis of various diseases. CONCLUSION: Metabonomics has great advantages in all aspects of the therapy of liver diseases, with good prospects for clinical application.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hepatopatías/metabolismo , Hígado/metabolismo , Medicina Tradicional China , Metabolómica/métodos , Fitoterapia , Biomarcadores , Humanos , Hígado/patologíaRESUMEN
Five pairs of new 2-oxoindole alkaloids, (±)-peganumalines A-E (1-5), and a new indole alkaloid, peganumaline F (6), along with two known analogues, were isolated from the seeds of Peganum harmala. Their structures and absolute configurations were elucidated through spectroscopic analyses and quantum chemistry calculations. Notably, (±)-peganumalines A (1) represent a pair of rare 2-oxoindole dimeric alkaloid enantiomer with the hitherto unknown carbon skeleton. All isolates were tested for antiproliferative and antibacterial activities.
Asunto(s)
Alcaloides Indólicos/química , Peganum/química , Semillas/química , Línea Celular Tumoral , Humanos , Alcaloides Indólicos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Three new diterpenoids, ebractenoids O~Q (1-3), and a new phenolic glucoside, γ-pyrone-3-O-ß-d-(6-galloyl)-glucopyranoside (4), together with 6 known compounds, were isolated from the 95% ethanol extract of the roots of Euphorbia ebracteolata, and their structures were elucidated on the basis of spectroscopic data. The absolute configurations of 1-3 were determined by electronic circular dichroism (ECD) calculations. The inhibitory effects of all the isolates with exception of compounds 8 and 10 on the NO production in lipopolysaccharide (LPS)-induced macrophages were evaluated. All of them exhibited significant inhibitory activity.
Asunto(s)
Diterpenos/química , Euphorbia/química , Glucósidos/química , Fenoles/química , Animales , Diterpenos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Fenoles/aislamiento & purificación , Raíces de Plantas/química , Células RAW 264.7RESUMEN
A new diphenyl ether 3-methylpentyl-2, 4-dichloroasterrate (2), along with a known diphenyl ether butyl 2, 4-dichloroasterrate (1) were isolated from the metabolites of a wetland fungus Aspergillus flavipes. PJ03-11. The structures of 1 and 2 were determined by extensive NMR and HR-ESI-MS experiments. Compounds 1 and 2 showed weak cytotoxic activity, but both of them showed no antimicrobial activity.
Asunto(s)
Antiinfecciosos/farmacología , Aspergillus/química , Hidroxibenzoatos/farmacología , Éteres Fenílicos/farmacología , Antiinfecciosos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Cristalografía por Rayos X , Evaluación Preclínica de Medicamentos/métodos , Células HL-60 , Humanos , Hidroxibenzoatos/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Éteres Fenílicos/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics.
Asunto(s)
Berberina/farmacología , Coptis/química , Compuestos de Mercurio/toxicidad , Metabolómica/métodos , Sustancias Protectoras/farmacología , Animales , Sangre/efectos de los fármacos , Sangre/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/prevención & control , Espectroscopía de Resonancia Magnética , Masculino , Metaboloma/efectos de los fármacos , Ratas Wistar , Orina/químicaRESUMEN
Two new amide compounds, mariamides A and B (1-2), were obtained together with fourteen known compounds from the seeds of milk thistle (Silybum marianum). Their structures were established on the basis of extensive 1D and 2D NMR analyses, as well as HR-ESI-MS data. Most of the compounds showed significant antioxidant activities than positive control in ABTS and FRAP assays. However, only amide compounds 1-4 showed moderate DPPH radical scavenging activity and compounds 7 and 16 showed the most potent activity against DPPH. Most of the compounds showed moderate to stronger α-glucosidase inhibitory activities. Nevertheless, only flavonoids showed strong PTP1B inhibitory activities. These results indicate a use of milk thistle seed extracts as promising antioxidant and antidiabetic agents.
Asunto(s)
Amidas/química , Depuradores de Radicales Libres/química , Hipoglucemiantes/química , Silybum marianum/química , Amidas/aislamiento & purificación , Flavonoides/química , Depuradores de Radicales Libres/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Humanos , Hipoglucemiantes/aislamiento & purificación , Estructura Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Semillas/química , alfa-GlucosidasasRESUMEN
Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new ß-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,ß-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 µM.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Alcaloides Indólicos/química , Alcaloides Indólicos/aislamiento & purificación , Peganum/química , Semillas/química , Antineoplásicos Fitogénicos/farmacología , Carbolinas/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Alcaloides Indólicos/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Three new butenolides containing 5-hydroxyfuran-2(5H)-one core, asperteretal A (1), asperteretal B (2), and asperteretal C (3), together with seven known butenolides (4-10), were obtained from an endophytic fungus Aspergillus terreus PR-P-2 isolated from the plant Camellia sinensis var. assamica. The structures of compounds 1-3 were elucidated on the basis of detailed spectroscopic analysis including UV, IR, HRESIMS, 1D and 2D NMR, and ECD spectra. Compounds 1, 3, 5 and 6-8 showed potent inhibitory effects on NO production in RAW 264.7 lipopolysaccharide-induced macrophages, and compounds 5 and 8 also exhibited moderate cytotoxicity against HL-60 cell line.
Asunto(s)
4-Butirolactona/análogos & derivados , Aspergillus/química , Camellia sinensis/microbiología , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Endófitos/química , Células HL-60 , Humanos , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMEN
In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by (1)H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, (1)H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized ß-carboline alkaloids, pegaharmines A-D (1-4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using ß-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.
Asunto(s)
Antineoplásicos Fitogénicos/química , Carbolinas/química , Oligodesoxirribonucleótidos/química , Peganum/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Secuencia de Bases , Vías Biosintéticas , Carbolinas/aislamiento & purificación , Carbolinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , G-Cuádruplex , Células HL-60 , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Peganum/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Semillas/químicaRESUMEN
Three new phenylnaphthalene-type lignans, vitexnegheteroins E-G (1-3), and a new polyoxygenated ursane-type triterpene, vitexnegheteroin H (9), were isolated from the seeds of Vitex negundo var. heterophylla, together with ten known compounds. Their structures were established on the basis of extensive 1D and 2D NMR experiments, as well as their mass spectroscopic data. The absolute configurations of compounds 1 and 2 were determined by comparing their experimental ECD spectra with that calculated by the time-dependent density functional theory (TDDFT) method. The isolates were evaluated for their cytotoxicities against three human cancer cell lines, inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells, and antioxidant activities for ABTS radical scavenging.
Asunto(s)
Lignanos/química , Triterpenos/química , Vitex/química , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/aislamiento & purificación , Humanos , Lignanos/aislamiento & purificación , Ratones , Microglía/efectos de los fármacos , Estructura Molecular , Óxido Nítrico/metabolismo , Triterpenos/aislamiento & purificaciónRESUMEN
Three new xanthones, paucinervins H-J (1-3), as well as eleven known compounds (4-14), were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds (1-3) were elucidated by 1D, 2D NMR spectra and HR ESIMS. In vitro antiproliferative activity against human promyelocytic leukemia HL-60 cells was tested, among which, compounds 2, 5, 6 and 7 exhibited strong growth inhibitory effects with GI50 values ranging from 1.30 to 9.08 µM, respectively. Preliminary SARs were also discussed.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Garcinia/química , Leucemia Promielocítica Aguda/tratamiento farmacológico , Extractos Vegetales/farmacología , Xantonas/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Células HL-60 , Humanos , Concentración 50 Inhibidora , Leucemia Promielocítica Aguda/metabolismo , Estructura Molecular , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Relación Estructura-Actividad , Xantonas/química , Xantonas/aislamiento & purificaciónRESUMEN
Three new prenylated xanthones, garcinexanthones G-I (1-3), together with fifteen known ones (4-18) were identified from the leaves of Garcinia lancilimba. Their structures were determined by extensive spectroscopic analyses. Most of the compounds exhibited inhibitory effects against HL-60 (human leukemia), A549 (human lung cancer), and MCF-7 (human breast cancer) cell lines. Among them, compounds 7, 17, and 13 exhibited the most pronounced growth inhibitory activity against HL-60, A549, and MCF-7 cell lines with GI50 values of 1.68, 4.88, and 6.28 µM, respectively.
Asunto(s)
Garcinia/química , Xantonas/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Células HL-60 , Humanos , Leucemia/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Células MCF-7 , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Prenilación , Xantonas/química , Xantonas/farmacología , Xantonas/uso terapéuticoRESUMEN
Four quinolone alkaloids (1-4) and three indole alkaloids (20-22), together with 30 known alkaloids (5-19, 23-37), were isolated from the fruits of Euodia rutaecarpa. Their structures were established by spectroscopic analyses. The in vitro cytotoxic activities of these alkaloids against leukaemia HL-60 and prostate cancer PC-3 cell lines were evaluated.
Asunto(s)
Antineoplásicos Fitogénicos/química , Evodia/química , Alcaloides Indólicos/química , Quinolonas/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Frutas/química , Células HL-60 , Humanos , Alcaloides Indólicos/aislamiento & purificación , Masculino , Estructura Molecular , Extractos Vegetales/química , Neoplasias de la Próstata/patología , Quinolonas/aislamiento & purificaciónRESUMEN
Thirteen diterpenoids (1-13), including two new norditerpene lactones (1-2) and eight new rosane diterpenoids (3-10), were isolated from the roots of Euphorbia ebracteolata. The structures were determined by 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD). The ECD-based empirical rule for α,ß-unsaturated-γ-lactones was applied to determine the absolute configurations of 1 and 2. Compounds 7, 10, and 13 exhibited significant inhibition of nitric oxide production in RAW 264.7 lipopolysaccharide-induced macrophages, with IC50 values of 2.44, 2.76, and 1.02 µM, respectively.
Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Euphorbia/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Animales , Antiinflamatorios/química , Diterpenos/química , Medicamentos Herbarios Chinos/química , Concentración 50 Inhibidora , Lactonas/química , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Resonancia Magnética Nuclear Biomolecular , Raíces de Plantas/química , EstereoisomerismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Zhusha Anshen Wan (ZSASW), a traditional Chinese medicine (TCM) prescription, composed of cinnabar (cinnabaris), Coptidis Rhizoma (Coptis chinensis French.), Angelicae Sinensis Radix (Angelica sinensis (oliv.) Diels), uncooked Rehmanniae Radix (Rehmannia glutinosa Libosch.), honey fried Glycyrrhizae Radix Et Rhizoma (Glycyrrhiza uralensis Fisch.), has been widely used for sedative therapy. Cinnabar, the chief component of ZSASW, has been proved to possess the toxicities. AIM OF THE STUDY: In this study, a metabonomics approach based on high-resolution (1)H nuclear magnetic resonance spectroscopy was applied to investigate the protective effects of ZSASW on the toxic effects induced by cinnabar alone. MATERIALS AND METHODS: Male Wistar rats were divided into three groups: control group, ZSASW group and cinnabar group. Partial least squares-discriminant analysis (PLS-DA) was performed to identify different metabolic profiles of urine and serum from rats. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. RESULTS: The significant difference in metabolic profiling of urine and serum of the rats was observed between cinnabar treated group, control group, and the changes of endogenous metabolites related to the toxicities were identified. The results were also certified by the liver and kidney histopathology examinations and biochemical analysis of blood. CONCLUSION: Our results suggested that the four combined herbal medicines of ZSASW had the effects of protecting from the toxicity induced by cinnabar alone. This work showed that the NMR-based metabonomics approach might be a promising approach to study detoxification of Chinese medicines and reasonable combination of TCM prescriptions.
Asunto(s)
Medicamentos Herbarios Chinos/toxicidad , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Compuestos de Mercurio/toxicidad , Metaboloma/efectos de los fármacos , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Biomarcadores/orina , Nitrógeno de la Urea Sanguínea , Riñón/patología , Hígado/patología , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas WistarRESUMEN
AIM: To study the metabolites of a halotolerant fungus Alternaria sp. M6. METHODS: The metabolites were isolated and purified by various chromatographic techniques. Their structures were determined on the basis of physical properties and spectroscopic data. RESULTS: Nine compounds were isolated and identified as 8ß-chloro-3, 6aα, 7ß, 9ß, 10-pentahydroxy-9, 8, 7, 6a-tetrahydroperylen-4(6aH)-one (1), alterperylenol (2), dihydroalterperylenol (3), adenine (4), adenosine (5), deoxyadenosine (6), guanosine (7), tryptophan (8), and hexadecanoic acid (9). CONCLUSION: Compound 1 is a new perylenequinone.
Asunto(s)
Alternaria/química , Productos Biológicos/aislamiento & purificación , Perileno/análogos & derivados , Quinonas/aislamiento & purificación , Alternaria/metabolismo , Productos Biológicos/química , Estructura Molecular , Perileno/química , Perileno/aislamiento & purificación , Quinonas/química , Tolerancia a la SalRESUMEN
Two new compounds, N-[4'-hydroxy-(E)-cinnamoyl]-l-tyrosine methyl ester (1) and methyl 4-methoxy-3-(3'-hydroxy-2'-methyl)propionyloxy-benzoate (2), were isolated from EtOAc extract of the fermentation broth of the endophytic fungus Aspergillus sp. HS-05. Their structures were elucidated by NMR, IR, UV, MS, and CD methods. Compounds 1 and 2 showed no anticancer activities against HL-60 cell lines (both of IC(50)>100 µM) in vitro.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Aspergillus/química , Benzoatos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Tirosina/análogos & derivados , Antineoplásicos/química , Antineoplásicos/farmacología , Benzoatos/química , Benzoatos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Tirosina/química , Tirosina/aislamiento & purificación , Tirosina/farmacologíaRESUMEN
Three new pregnanes, 21-hydroxypregna-4,6-diene-3,12,20-trione (1), 20R-hydroxypregna-4,6-diene-3,12-dione (2), and 16beta,17beta-epoxy-12beta-hydroxypregna-4,6-diene-3,20-dione (3), were isolated from Nerium oleander, together with two known compounds, 12beta-hydroxypregna-4,6,16-triene-3,20-dione (neridienone A, 4) and 20S,21-dihydroxypregna-4,6-diene-3,12-dione (neridienone B, 5). The structures of compounds 1-3 were established on the basis of their spectroscopic data. The anti-inflammatory activity in vitro of compounds 2-4 was examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1), and compound 4 was active. The cytotoxic activity of compounds 1-5 was evaluated against four human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), human liver tumor cells (HepG2), and human lung carcinoma cells (A-549). Compound 4 showed significant cell growth inhibition of VA-13 and HepG2 cells. The MDR-reversal activity of compounds 1-5 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 1, 2, and 5 showed significant effects on calcein accumulation.