clove and Ovarian-Neoplasms

Sideroxylin is a C-methylated flavone isolated from Callistemon lanceolatus and exerts antimicrobial activity against Staphylococcus aureus. However, the anticancer effects of sideroxylin and its intracellular signaling mechanisms have not yet been identified. Results of our study showed that sideroxylin decreased cell proliferation and increased apoptosis, causing DNA fragmentation, depolarization of the mitochondrial membrane, the generation of reactive oxygen species, and an increase of lipid peroxidation in ovarian cancer cells (ES2 and OV90 cells). Additionally, sideroxylin activated the phosphorylation of ERK1/2, JNK, P38, and MAPK proteins and the use of LY294002, U0126, SB203580, and SP600125 to block their phosphorylation, respectively, in ES2 and OV90 cells. Collectively, the results of present study indicated that sideroxylin was a novel therapeutic agent to combat the proliferation of ovarian cancer cells through the induction of mitochondrial dysfunction and the activation of PI3 K and MAPK signal transduction.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Female; Flavonoids; Humans; Lipid Peroxidation; MAP Kinase Signaling System; Mitochondria; Myrtaceae; Ovarian Neoplasms; Oxidative Stress; Phosphorylation; Reactive Oxygen Species

An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (-)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 µM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Diterpenes; Female; Forests; Humans; Inhibitory Concentration 50; Madagascar; Meliaceae; Molecular Structure; Ovarian Neoplasms

Investigation of the endemic Madagascan plant Nematostylis anthophylla (Rubiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the known triterpene saponin randianin (1), and the two new bioactive triterpene saponins 2"-O-acetylrandianin (2) and 6"-O-acetylrandianin (3). The structures of the two new compounds were elucidated based on analysis of their 1D- and 2D-NMR spectra, and mass spectrometric data. The three isolated triterpene saponins displayed moderate but selective antiproliferative activities, with IC(50) values of 1.2, 1.7, and 2.2 μM, respectively, against the A2780 ovarian cancer, but only weak inhibitions of the proliferation of A2058 melanoma and the H522 lung cancer cell lines.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Female; Humans; Lung Neoplasms; Madagascar; Melanoma; Ovarian Neoplasms; Rubiaceae; Saponins; Triterpenes

Investigation of the endemic Madagascan plant Sterculia taiva Baill. (Malvaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of two new bioactive calamenene-type sesquiterpenoids, named tavinin A (2) and epi-tavinin A (3) together with the known sesquiterpenoid mansonone G (1). The structures of the two new compounds were elucidated based on analysis of their 1D and 2D NMR spectra and mass spectrometric data, and were confirmed by de novo synthesis. The three isolated sesquiterpenoids (1-3) had modest antiproliferative activities against the A2780 ovarian cancer cell line, with IC(50) values of 10.2, 5.5 and 6.7 μM, respectively.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Drug Screening Assays, Antitumor; Female; Humans; Madagascar; Ovarian Neoplasms; Plant Extracts; Polycyclic Sesquiterpenes; Sesquiterpenes; Sterculia; Terpenes

Investigation of the endemic Madagascar plant Leptadenia madagascariensis Decne. (Apocynaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the four new cardenolides 1-4. The structure elucidations of these compounds were based on analyzes of their 1D and 2D NMR spectra and mass spectrometric data. The cardenolides were strongly antiproliferative to the A2780 ovarian cancer cell line, with IC(50) values of 0.18, 0.21, 0.17, and 0.29μM line, and to the H460 human lung cancer cell line, with IC(50) values of 0.16, 0.68, 0.37, and 0.48μM, respectively.

Topics: Apocynaceae; Cardenolides; Cell Line, Tumor; Cell Proliferation; Female; Humans; Madagascar; Ovarian Neoplasms

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 μM (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; Humans; Madagascar; Ovarian Neoplasms; Plant Extracts; Trees; Vitaceae

A study of an EtOH extract obtained from the roots of the Madagascan plant Terminalia tropophylla H. Perrier (Combretaceae) led to isolation of the oleanane-type triterpenoid saponin 1, the lignan derivative 2, and the two known saponins arjunglucoside I (3) and sericoside (4). The structures of compounds 1 (terminaliaside A) and 2 (4'-O-cinnamoyl cleomiscosin A) were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compound 1 showed antiproliferative activity against the A2780 human ovarian cancer cell line with an IC(50) value of 1.2 microM.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Ecosystem; Female; Humans; Inhibitory Concentration 50; Lignans; Madagascar; Molecular Structure; Oleanolic Acid; Ovarian Neoplasms; Phytotherapy; Plant Extracts; Plant Roots; Saponins; Terminalia; Triterpenes

Fractionation of an ethanol extract of a Madagascar collection of the leaves and fruit of Cassipourea lanceolata Tul. led to the isolation of three euphane triterpenoids 1-3. The (1)H and (13)C NMR spectra of all compounds were fully assigned using a combination of 2D NMR experiments, including COSY, TOCSY, HSQC (HMQC), HMBC and ROESY sequences. The three compounds showed weak antiproliferative activities against the A2780 human ovarian cancer cell line, with IC(50) values of 25, 25 and 32 microM, respectively.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Female; Fruit; Humans; Inhibitory Concentration 50; Madagascar; Molecular Structure; Ovarian Neoplasms; Phytotherapy; Plant Extracts; Plant Leaves; Rhizophoraceae; Triterpenes

Bioassay-guided fractionation of an EtOH extract obtained from the roots of the Madagascan plant Albizia gummifera led to the isolation of three new cytotoxic oleanane-type triterpenoid saponins, gummiferaosides A-C (1-3). The structures of these new compounds were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1-3 showed cytotoxicity against the A2780 human ovarian cancer cell line with IC50 values of 0.8, 1.5, and 0.6 microg/mL, respectively.

Topics: Albizzia; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Female; Humans; Inhibitory Concentration 50; Madagascar; Molecular Structure; Ovarian Neoplasms; Plants, Medicinal; Saponins; Triterpenes

Bioassay-guided fractionation of an extract of the fruit of Macaranga alnifolia from Madagascar led to the isolation of four new prenylated stilbenes, schweinfurthins E-H (1-4), and one new geranylated dihydroflavonol, alnifoliol (5). The known prenylated stilbene vedelianin (6) and the known geranylated flavonoids bonanniol A (7), diplacol (8), bonannione A (9), and diplacone (10) were also isolated. All 10 compounds were tested for antiproliferative activity in the A2780 human ovarian cancer cell line assay. Vedelianin (IC50 = 0.13 microM) exhibited the greatest activity among all isolates, while schweinfurthin E (IC50 = 0.26 microM) was the most potent of the new compounds.

Topics: Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Euphorbiaceae; Female; Flavonoids; Humans; Madagascar; Ovarian Neoplasms; Plants, Medicinal; Stilbenes; Tumor Cells, Cultured

Bioassay-guided fractionation of the root and stem extracts of Mendoncia cowanii led to the isolation of two new and two known naphthoquinones. The structures of the new compounds, avicequinones D and E (1 and 2), were determined using 1D and 2D NMR spectroscopy and by chemical conversion of compound 1 to 2. The new compounds were active in the A2780 human ovarian cancer cell line with IC50 values of 7.4 - 50 microM, respectively, and 1, 3, and 4 were subsequently found to be weakly active in an assay for inhibition of the kinase Akt.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Female; Humans; Inhibitory Concentration 50; Madagascar; Magnoliopsida; Medicine, Traditional; Naphthoquinones; Ovarian Neoplasms; Phytotherapy; Plant Extracts; Plant Roots; Plant Stems; Trees

Bioassay-directed fractionation of an extract of the root and bark of Podocarpus madagascariensis resulted in the isolation of a new totarol diterpenoid (1) in addition to the three known cytotoxic diterpenoids 19-hydroxytotarol (2), totaradiol (3), and 4beta-carboxy-19-nor-totarol (4). The structure of the new compound 1 was established as methyl-13-hydroxy-14-isopropyl-9(11),12,14(8)-podocarpatriene-19-oate on the basis of 1D and 2D NMR spectroscopic interpretation and methylation of 4. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cycadopsida; Diterpenes; Ecosystem; Female; Humans; Madagascar; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Bark; Plant Roots; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet

Two new flavanones, remangiflavanones D and E (1 and 2), were isolated from an extract of the twigs, leaves, and flowers of Physena madagascariensis together with three known flavanones, remangiflavanones A-C (3-5), and (E)-N-feruloyltyramine (6). The structures of the new compounds 1 and 2 were established on the basis of one-dimensional and two-dimensional NMR spectroscopic data interpretation. All compounds were evaluated for their cytotoxicity in the A2780 human ovarian cancer cell line. Compound 5 was the most active with an IC50 value of 2.5 microg mL-1.

Topics: Antineoplastic Agents, Phytogenic; Caryophyllaceae; Cell Line, Tumor; Circular Dichroism; Cytotoxins; Female; Flavanones; Humans; Inhibitory Concentration 50; Madagascar; Mass Spectrometry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Components, Aerial; Plant Extracts; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

Bioassay-directed fractionation of the alkaloid portion of a CH(2)Cl(2)-MeOH extract of Tabernaemontana calcarea resulted in the isolation of the three new cytotoxic indole alkaloids, 1-3, and the 12 known alkaloids voacangine (4), isovoacangine (5), coronaridine (6), 11-hydroxycoronaridine (7), voacristine (8), 19-epi-voacristine (9), isovoacristine (10), ibogamine (11), 10-methoxyibogamine (12), 11-methoxyibogamine (13), heyneanine (14), and 19-epi-heyneanine (15). The structures of the new compounds 1-3 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic interpretation. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.

Topics: Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Female; Humans; Indole Alkaloids; Madagascar; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Tabernaemontana; Tumor Cells, Cultured

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the wood of Vepris punctata resulted in the isolation of three new furoquinoline alkaloids, 5-methoxymaculine (1), 5,8-dimethoxymaculine (2), and 4,5,6,7,8-pentamethoxyfuroquinoline (3), in addition to the four known alkaloids flindersiamine (4), kokusaginine (5), maculine (6), and skimmianine (7). The structures of the new alkaloids 1-3 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All the isolated compounds were tested against the A2780 human ovarian cancer cell line, and all seven alkaloids showed weak cytotoxic activity.

Topics: Antineoplastic Agents, Phytogenic; Female; Humans; Madagascar; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Rutaceae; Tumor Cells, Cultured; Wood

Bioassay-guided fractionation of an ethanolic extract of the infructescences of Polyscias amplifolia resulted in the isolation of two new oleanolic acid saponins, polyfoliolides A (1) and B (2), in addition to the two known saponins 3-O-beta-D-galactopyranosyloleanolic acid (3) and 3-O-beta-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyloleanolic acid (4). The structures of the two new compounds were established as 3-O-beta- D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyloleanolic acid (1) and 3-O-beta-D-galactopyranosyl-(1-->4)-alpha-L-arabinopyranosyloleanolic acid (2) on the basis of extensive 1D and 2D NMR spectroscopic data interpretation and chemical conversions. All the isolated compounds showed weak cytotoxicity against A2780 human ovarian cancer cell line, with IC50 values in the range 6.7 to 10.8 microg/mL.

Topics: Antineoplastic Agents; Araliaceae; Female; Humans; Inhibitory Concentration 50; Madagascar; Medicine, Traditional; Ovarian Neoplasms; Phytotherapy; Plant Extracts; Saponins; Tumor Cells, Cultured

Bioassay-guided fractionation of a CH2Cl2-MeOH extract of the bark of Ochrocarpos punctatus resulted in the isolation of seven new coumarins, ochrocarpins A-G (1-7), three new benzophenone derivatives, ochrocarpinones A-C (8-10), and five known coumarins, mammea A/AC cyclo F (11), mammea A/AD cyclo D (12), mammea A/AB cyclo F (13), mammea A/AA cyclo F (14), mammea A/AB cyclo D (15), and 15,16-dihydro-16-hydroperoxyplukenetione (16). The structures of compounds 1-10 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All compounds exhibited cytotoxicity against the A2780 ovarian cancer cell line.

Topics: Antineoplastic Agents, Phytogenic; Benzophenones; Clusiaceae; Coumarins; Drug Screening Assays, Antitumor; Female; Humans; Inhibitory Concentration 50; Madagascar; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Tumor Cells, Cultured

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the small twigs of Brachylaena ramiflora var. ramiflora resulted in the isolation of the two new triterpene esters 1 and 2 and five known triterpenoids, alpha-amyrin palmitate (3), beta-amyrin palmitate (4), beta-amyrin acetate (5), lupeyl acetate (6), and lupeol (7). The structures of the two new compounds were established as kairatenyl palmitate (1) and hopenyl palmitate (2) on the basis of 1D and 2D NMR spectroscopic data interpretation and chemical conversions. All the isolated compounds showed weak cytotoxicity against the A2780 human ovarian cancer cell line.

Topics: Antineoplastic Agents, Phytogenic; Asteraceae; Drug Screening Assays, Antitumor; Esters; Female; Humans; Inhibitory Concentration 50; Madagascar; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oleanolic Acid; Ovarian Neoplasms; Palmitates; Pentacyclic Triterpenes; Plant Shoots; Plants, Medicinal; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Triterpenes; Tumor Cells, Cultured

Bioassay-directed fractionation of a CH(2)Cl(2)-MeOH extract of the leaves of Oncostemon bojerianum resulted in the isolation of eight new 5-alkylresorcinols, named oncostemonols A-H (1-8), and two known derivatives, (8'Z)-1,3-dihydroxy-5-[16'-(3' ',5' '-dihydroxyphenyl)-8'-hexadecen-1'-yl]benzene (9) and (8'Z)-1,3-dihydroxy-5-[14'-(3' ',5' '-dihydroxyphenyl)-8'-tetradecen-1'-yl]benzene (10). The structures of the new compounds 1-8 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical derivatization. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.

Topics: Acetylation; Antineoplastic Agents, Phytogenic; Drug Screening Assays, Antitumor; Female; Humans; Inhibitory Concentration 50; Madagascar; Methylation; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Leaves; Plants, Medicinal; Primulaceae; Resorcinols; Stereoisomerism; Tumor Cells, Cultured

A novel triterpenoid saponin, pittoviridoside (1), which possesses an unusual 2,3,4-trisubstituted glycosidic linkage, has been isolated from Pittosporum viridiflorum using the engineered yeast strains 1138, 1140, 1353, and Sc-7 for bioactivity-guided fractionation. The structure of this compound was determined to be 3-O-[beta-D-glucopyranosyl(1-->2)]-[alpha-D-arabinopyranosyl(1-->3)],[alpha-l-arabinofuranosyl(1-->4)-beta-D-glucuronopyranosyl-21-angeloyl-22-senecioylolean-12-en-3beta,15alpha,16alpha,21beta,22alpha,28-hexol by spectral, chemical, and GC analyses. This compound showed weak cytotoxicity against the A2780 human ovarian cancer cell line.

Topics: Antineoplastic Agents, Phytogenic; Chromatography, Thin Layer; Drug Screening Assays, Antitumor; Female; Gas Chromatography-Mass Spectrometry; Humans; Hydrolysis; Madagascar; Nuclear Magnetic Resonance, Biomolecular; Oleanolic Acid; Ovarian Neoplasms; Plants, Medicinal; Saccharomyces cerevisiae; Saponins; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Structure-Activity Relationship; Triterpenes; Tumor Cells, Cultured

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the bark of Casearia lucida resulted in the isolation of 11 new clerodane diterpenes, namely, casearlucins A-K (1-11), and three known clerodane diterpenoids, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (12), rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (13), and rel-(2S,5R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (14). The structures of compounds 1-11 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All compounds exhibited cytotoxicity activity against the A2780 ovarian cancer cell line, but none of the six compounds selected for testing in multiple cell lines showed significant selectivity.

Topics: Animals; Antineoplastic Agents, Phytogenic; Aorta, Thoracic; Breast Neoplasms; Cattle; Cells, Cultured; Colonic Neoplasms; Diterpenes; Drug Screening Assays, Antitumor; Female; HT29 Cells; Humans; Inhibitory Concentration 50; Leukemia; Lung Neoplasms; Madagascar; Magnoliopsida; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Bark; Plants, Medicinal; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Stereoisomerism; Tumor Cells, Cultured

Nine tropane alkaloid aromatic esters (1-9) were isolated from the roots of Erythroxylum pervillei by following their potential to reverse multidrug-resistance with vinblastine-resistant oral epidermoid carcinoma (KB-V1) cells. All isolates, including seven new structures (3-9), were evaluated against a panel of human cancer cell lines, and it was found that alkaloids 3 and 5-9 showed the greatest activity with KB-V1 cells assessed in the presence of vinblastine, suggesting that these new compounds are potent modulators of P-glycoprotein. Confirmatory results were obtained with human ovarian adenocarcinoma (SKVLB) cells evaluated in the presence of adriamycin and synergistic studies performed with several cell lines from the NCI tumor panel. The structures of the new compounds were determined using spectroscopic techniques. Single-crystal X-ray analysis was performed on the monoester, tropane-3 alpha,6 beta,7 beta-triol 3-phenylacetate (1).

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B; Crystallography, X-Ray; Doxorubicin; Drug Resistance, Multiple; Drug Screening Assays, Antitumor; Erythroxylaceae; Esters; Female; Humans; Madagascar; Medicine, Traditional; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plant Roots; Plants, Medicinal; Spectrophotometry, Infrared; Stereoisomerism; Tropanes; Tumor Cells, Cultured