ABSTRACT
Seven undescribed sesquiterpene lactone dimers (SLDs) (carpeabrodilactones A-G), one known SLD, and six known sesquiterpenes were isolated from the fruit of Carpesium abrotanoides L. Carpeabrodilactone A was a dimeric carabrane featuring a rare C-13-C-13' linkage. Carpeabrodilactones B and C are the first two SLDs to be described possessing a carabranolide unit and a guaianolide unit connected by an O-ether linkage. The structures of the SLDs were assigned based on HRESIMS, NMR analysis, 13C NMR calculation, ECD calculation, and modified Mosher's method. Four SLDs showed potent cytotoxicity against K562 and/or A549 cells, with IC50 values below 10 µM, but none inhibited protein tyrosine phosphatases at 40 µM, including PTP1B, SHP1, CD45, and TCPTP.
Subject(s)
Asteraceae , Sesquiterpenes , Asteraceae/chemistry , Ethers , Fruit , Lactones/chemistry , Lactones/pharmacology , Molecular Structure , Phytochemicals , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
Two tetranortriterpenoids with new skeletons, xylomexicanins I and J (1 and 2), were isolated during the investigation of chemical constituents from seeds of the Chinese mangrove, Xylocarpus granatum. Xylomexicanin I (1) is an unprecedented limonoid with bridged B- and C-rings. A biosynthesis pathway for 1 from xylomexicanin F is proposed.
Subject(s)
Limonins/isolation & purification , Meliaceae/chemistry , Seeds/chemistry , Limonins/chemistry , Molecular StructureABSTRACT
The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bridged-Ring Compounds/chemistry , Diterpenes/chemistry , Diterpenes/pharmacology , Taxoids/chemistry , Taxus/chemistry , Uterine Cervical Neoplasms/pathology , Apoptosis/drug effects , Cell Proliferation/drug effects , Female , HeLa Cells , Humans , Hydrophobic and Hydrophilic InteractionsABSTRACT
Eupatorium (family: Compositae), which comprises nearly 1200 species, is distributed throughout tropical America, Europe, Africa, and Asia. Up to now, the reported constituents from the genus Eupatorium involve flavonoids, terpenoids, pyrrolizidine alkaloids, phenylpropanoids, quinonoids, essential oils, and some others, altogether more than 300 compounds. Studies have shown that Eupatorium and its active principles possess a wide range of pharmacological activities, such as cytotoxic, antifungal, insecticidal, antibacterial, anti-inflammatory, and antinociceptive activities. Currently, effective monomeric compounds or active parts have been screened for pharmacological activities from Eupatorium in vivo and in vitro. Increasing amount of data supports application and exploitation for new drug development.
Subject(s)
Analgesics/pharmacology , Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Eupatorium/chemistry , Organic Chemicals/pharmacology , Plant Extracts/pharmacology , Analgesics/chemistry , Analgesics/isolation & purification , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Humans , Organic Chemicals/chemistry , Organic Chemicals/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purificationABSTRACT
There is an ongoing search for plant-derived sesquiterpenes, particularly for those with anticancer activity against human cancer cells. The sesquiterpene ineupatorolide B (InB), isolated from the Inula cappa, showed potent growth-inhibitory activity against HeLa cells but less activity against MM1-CB melanoma cells. Staining by terminal deoxynucleotidyl transferase dUTP nick-end labeling method revealed that this activity was, at least in part, due to the induction of apoptosis. The activities of major transcription factors were examined by using a luciferase reporter assay. The results showed that the transactivation ability of nuclear factor of activated T-cell (NFAT) was enhanced. The activation of NFAT by InB was largely suppressed by preincubation with protein kinase C (PKC) inhibitors such as staurosporine and K252a. Western blot analysis revealed that the the levels of phosphorylated PKCα, but not other subtypes, increased after treatment with InB. Knockdown of PKCα using siRNA attenuated the cytotoxic activity of InB. Thus, InB may exhibit growth-inhibitory activity through the activation of PKCα, followed by an increase in NFAT transactivation ability.
Subject(s)
NFATC Transcription Factors/genetics , Protein Kinase C-alpha/biosynthesis , Sesquiterpenes/administration & dosage , Uterine Cervical Neoplasms/genetics , Apoptosis/drug effects , Female , HeLa Cells , Humans , Inula/chemistry , NFATC Transcription Factors/biosynthesis , Phosphorylation , Protein Kinase C-alpha/genetics , RNA, Small Interfering , Uterine Cervical Neoplasms/pathologyABSTRACT
A rapid and sensitive high-performance liquid chromatographic (HPLC) method was developed for the simultaneous separation and determination of chlorogenic acid, caffeic acid, alantolactone and isoalantolactone in Inula helenium. The HPLC separation was performed on an Elite Hypersil C18 column (200 × 4.6 mm i.d., 5 µm particle size) with a gradient elution of solvent A (acetonitrile) and solvent B (0.1% phosphoric acid in water) at a flow rate of 1.0 mL/min. Detection was monitored at 225 nm. The recovery of chlorogenic acid ranged from 95.6 to 107.7%, the recovery of caffeic acid ranged from 95.4 to 104.2%, the recovery of alantolactone ranged from 95.8 to 100.8% and the recovery of isoalantolactone ranged from 96.5 to 102.3%. The retention times for chlorogenic acid, caffeic acid, alantolactone and isoalantolactone were 5.2, 7.1, 25.6 and 26.6 min with the limits of detection of 0.069, 0.021, 0.039 and 0.051 µg/mL, respectively. Relative standard deviation for the intra-day and inter-day was ≤2.5%. The validated method is reliable for the routine control of these four compounds in I. helenium.
Subject(s)
Caffeic Acids/analysis , Chlorogenic Acid/analysis , Chromatography, High Pressure Liquid/methods , Inula/chemistry , Lactones/analysis , Plant Extracts/chemistry , Sesquiterpenes, Eudesmane/analysis , Limit of Detection , Linear Models , Reproducibility of ResultsABSTRACT
A new sesquiterpene, eudesm-11-ene-4alpha,7beta,9beta-triol, was isolated from the EtOH extract of aerial parts of Dichrocephala integrifolia. Its structure was determined on the basis of spectral analysis of 1D and 2D NMR data.
Subject(s)
Asteraceae/chemistry , Sesquiterpenes, Eudesmane/isolation & purification , Magnetic Resonance Spectroscopy , Sesquiterpenes, Eudesmane/chemistryABSTRACT
A series of new taxanes, 1-93, have been isolated, together with 37 known taxoids including Taxol(®) (paclitaxel) and cephalomannine, from the Canadian yew, Taxus canadensis (Taxaceae) in the past 30 years. These new taxoids possess various skeletons containing 5/7/6, 6/10/6, 6/5/5/6, 6/8/6, and 6/12 ring systems and six new taxanes with four novel skeletons, i.e., a taxane with a 6/6/8/6 ring system, a taxane with a [3.3.3] propellane skeleton, three taxanes with [3.3.3] [3.4.5] dipropellane sytems, as well as a novel taxane with a unique 5/5/4/6/6/6 hexacyclic skeleton, containing a unique [3.3.2] propellane, were isolated for the first time from natural sources. It should be emphasized that 13-acetyl-9-dihydrobaccatin III, a very useful starting material for the semisynthesis of Taxol(®) and Taxotere(®) , represents the most abundant taxane in the needles of this yew tree. These findings establish the above mentioned yew tree as significantly different from the remaining species. On the other hand, some chemical modifications on the taxanes isolated from this plant were carried out.
Subject(s)
Plant Extracts/chemistry , Taxus/chemistry , Cell Survival/drug effects , Drug Resistance, Neoplasm/drug effects , Humans , Isomerism , MCF-7 Cells , Molecular Conformation , Taxoids/chemistry , Taxoids/isolation & purification , Taxoids/toxicity , Taxus/metabolismABSTRACT
Two new limonoids, named xylomexicanins C and D, were isolated from a dichloromethane extract of the seeds of Xylocarpus granatum cultivated in Hainan, China, and their structures were elucidated on the basis of one- and two-dimensional NMR (including 1H, 13C-NMR, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY) and confirmed by high-resolution mass spectrometry. Xylomexicanin C exhibited antiproliferative activity against human breast carcinoma cells (KT).
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Limonins/chemistry , Limonins/pharmacology , Meliaceae/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Humans , Limonins/isolation & purificationABSTRACT
OBJECTIVE: To study the chemical constituents in the needles of Taxus cuspidata collected from Japan. METHODS: Chemical constituents were isolated by column chromatography, TLC and preparative HPLC. The structures were identified on the basis of NMR spectral analysis. RESULTS: Six non-taxoids were isolated and identified as: 4-[(1E)-3-hydroxy-1-buten-1-yl]-3,5,5-trimethyl-2-cyclohexen-1-one (1), megastigm-5-ene-3, 9-diol (2), 6alpha-epoxy-7-megastigmen-9-one (3), 4-(4-hydroxyphenyl)-2-butanone (4), 12-hydroxy-alpha-cyperone (5), scutellarein-7-O-alpha-L-rhamnoside (6). CONCLUSION: Compounds 2 - 6 are isolated from Taxus genus for the first time. Compound 1 is obtained from Taxus cuspidata for the first time.
Subject(s)
Taxus/chemistry , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , TaxoidsABSTRACT
A phytochemical investigation of Chromolaena odorata resulted in the isolation of five new compounds, 5aα,6,9,9aß,10-pentahydro-10ß-hydroxy-7-methylanthra[1,2-d][1,3]dioxol-5-one (1), 1,2-methylenedioxy-6-methylanthraquinone (2), 3-hydroxy-1,2,4-trimethoxy-6-methylanthraquinone (3), 3-hydroxy-1,2-dimethoxy-6-methylanthraquinone (4), and 7-methoxy-7-epi-medioresinol (5), together with 12 known compounds, odoratin (6), 3ß-acetyloleanolic acid (7), ursolic acid (8), ombuin (9), 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (10), (-)-pinoresinol (11), austrocortinin (12), tianshic acid (13), cleomiscosin D (14), (-)-medioresinol (15), (-)-syringaresinol (16), and cleomiscosin A (17). All the compounds were evaluated for their PPARγ transactivation activity, and compound 6 showed moderate activity with an EC(50) value of 3.10 µM.
Subject(s)
Anthraquinones/isolation & purification , Chromolaena/chemistry , Dioxoles/isolation & purification , Dioxoles/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Flavonoids/isolation & purification , Flavonoids/pharmacology , Lignans/isolation & purification , Lignans/pharmacology , PPAR gamma/agonists , Anthraquinones/chemistry , Anthraquinones/pharmacology , Dioxoles/chemistry , Drugs, Chinese Herbal/chemistry , Flavonoids/chemistry , Furans/chemistry , Furans/isolation & purification , Hepatocytes/drug effects , Humans , Lignans/chemistry , Luciferases/metabolism , Molecular Structure , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , StereoisomerismABSTRACT
Eight sesquiterpene lactones were isolated from the roots of Inula helenium and flowers of I. japonica. Among them, isoalantolactone (3) and santamarine (6) exhibited significant growth inhibitory activities against gynecologic cancer cell lines, while others weakly inhibited the growth of the cell lines (IC50 < or = 100 microM). In addition, 3 significantly inhibited the tumour growth of S180 tumour-bearing mice. Compounds 3 and 6 were not toxic to human embryonic lung fibroblast cells in vitro. These results demonstrated that the antitumour activities are closely related to the structures of the compounds, that is, an alpha-exomethylene-gamma-lactone ring is necessary for these activities.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Inula/chemistry , Lactones/pharmacology , Sesquiterpenes/chemistry , Cell Line, Tumor , HumansSubject(s)
Plant Extracts/pharmacology , Plant Structures/chemistry , Salvia/chemistry , Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Bacteria/drug effects , Cell Survival/drug effects , Humans , Sesquiterpenes/chemistry , Sesquiterpenes, Germacrane/chemistry , Viruses/drug effectsABSTRACT
Paclitaxel (Taxol), one of the most potent anticancer drugs, is a microtubule-stabilizing compound that inhibits microtubule depolymerization within the cell. The structure of paclitaxel is composed of two key elements, a taxane ring and an N-benzoylphenylisoserine side chain at C-13. A number of natural and artificial compounds with taxane skeletons have been isolated, but almost none of their bioactivities have been evaluated. In this study, we focused on compounds having a taxane skeleton structure and examined their effects on tubulin dynamics. Although none of these compounds had an N-benzoylphenylisoserine side chain, three were found to promote tubulin assembly. On the other hand, one compound inhibited tubluin assembly in a way similar to nocodazole. These compounds exhibited novel structure-activity relationships of taxane compounds.
Subject(s)
Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/pharmacology , Microtubules/drug effects , Taxoids/chemistry , Taxoids/pharmacology , Animals , Antineoplastic Agents , Humans , Microtubules/metabolism , Molecular Structure , Nocodazole , Paclitaxel , Polymerization , Structure-Activity Relationship , TubulinSubject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Paclitaxel/pharmacology , Taxaceae/chemistry , Taxoids/chemistry , Taxoids/isolation & purification , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/chemistry , Geography , Humans , Mass Spectrometry , Nuclear Magnetic Resonance, Biomolecular , Paclitaxel/analogs & derivatives , Structure-Activity Relationship , Taxaceae/classificationABSTRACT
OBJECTIVE: To study prescription and technique of intragastric floating two-chamber osmotic pump tablets (TCOPT) of total alkaloids of Coptis chinensis and Evodia rutaecarpa and inspect release property in vitro. METHODS: The orthogonal experiment was designed to screen prescription and technique. RESULTS: The optimization of prescription and technique were as follows: the expanding agent was a mixture of PEO and HPMC as a ratio of 4:1; the osmotic agent in propelling layer contained sodium chloride 20 mg, PEG 400 in the cellulose acetate, 10%; coating membrane in core tablet, 9%. The release behavior of TCOPT coincidented with zero-level equation well and the character of controlled-release was transparent. CONCLUSION: TCOPT has good effect of controlled-release in vitro and the release behavior in vivo need to be inspected.
Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacokinetics , Coptis/chemistry , Evodia/chemistry , Gastric Mucosa/metabolism , Technology, Pharmaceutical/methods , Alkaloids/administration & dosage , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Delivery Systems , Drug Stability , Excipients/chemistry , Fruit/chemistry , Osmosis , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemistry , Rhizome/chemistry , Sodium Chloride/chemistry , Solubility , TabletsABSTRACT
A novel 6/8/6-membered taxane with a rare C-12(13)-double bond and rare 2(3â20)abeotaxane were isolated from the needles of Taxus canadensis. Their structures were characterized as 7ß,9α,10ß-triacetoxytaxa-4(20),12-diene-2α,5α,11ß-triol (1) and 2α,7ß,10ß-triacetoxy-5α-hydroxy-2(3â20)abeotaxa-4(20),11-diene-9,13-dione (2) on the basis of 1D and 2D spectroscopic data. 1 is the first example of a natural taxane without substitution at both C-13 and C-14.
Subject(s)
Antineoplastic Agents/analysis , Plant Extracts/analysis , Taxoids/analysis , Taxus/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Magnetic Resonance Spectroscopy , Male , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Leaves/chemistry , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Taxoids/chemistry , Taxoids/isolation & purification , Taxoids/pharmacology , Treatment Failure , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathologyABSTRACT
Achillinin A (2ß,3ß-epoxy-1α,4ß,10α-trihydroxyguai-11(13)-en-12,6α-olide, 1), a new guaianolide isolated from the flower of Achillea millefolium, exhibited potential antiproliferative activity to A549, RERF-LC-kj and QG-90 cells with 50% inhibitory concentration (IC(50)) values of 5.8, 10 and 0.31 µM, respectively.
Subject(s)
Achillea/chemistry , Adenocarcinoma/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Sesquiterpenes/pharmacology , Small Cell Lung Carcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Survival/drug effects , Flowers/chemistry , Humans , Inhibitory Concentration 50 , Lung Neoplasms/pathology , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Sesquiterpenes/chemistry , Sesquiterpenes/therapeutic use , Small Cell Lung Carcinoma/pathologySubject(s)
Senecio/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Alkanes/chemistry , Alkanes/pharmacology , Coumarins/chemistry , Coumarins/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Hydroxybenzoates/chemistry , Hydroxybenzoates/pharmacology , Monoterpenes/chemistry , Monoterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Steroids/chemistry , Steroids/pharmacology , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Three new taxanes, 2 α,9 α,10 ß-triacetoxy-13 α-( ß-D-glucopyranosyloxy)taxa-4(20),11-dien-5 α-ol, 5 α,10 ß,13 α-triacetoxytax-11-ene-2 α,7 ß,9 α,20-tetraol, and 5 α,10 ß,13 ß-triacetoxy-2 α,7 ß-dihydroxy-2(3â20) abeotaxa-4(20),11-dien-9-one, were isolated from the leaves of the Japanese yew, Taxus cuspidata. Compound 1 is the first example of a taxane with 13-glycosidic linkage.