benzofurans and Leukemia-P388

Goniothalamus macrophyllus (Blume) Hook. f. & Thoms. is a plant widely distributed in Malaysia. The aim of this study is to identify compounds from the roots of G. macrophyllus. The ground roots were extracted with aqueous methanol and partitioned sequentially with n-hexane, chloroform and butanol. Purification from this extracts afforded six compounds with two new compounds, namely goniolandrene-A (1), -B (2). The absolute configuration of goniolandrene B (2) was established by circular dichrosim. The compounds were cytotoxic against the P388 cells with IC50 values ranging from 0.42 to 160 μM. Goniothalamin (3) exhibited the highest inhibition of 0.42 μM.

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Cell Line, Tumor; Chromones; Goniothalamus; Heterocyclic Compounds, 3-Ring; Inhibitory Concentration 50; Leukemia P388; Malaysia; Molecular Structure; Phytotherapy; Plant Extracts; Plant Roots; Pyrones

A new 2-arylbenzofuran derivative (diptoindonesin G) (1), along with nine known oligostilbenes, have been isolated and identified from the acetone extract of the tree bark of Hopea mengarawan. The structures of these compounds were determined based on spectroscopic data, including 2D NMR and HREIMS spectra. On cytotoxic evaluation of the isolated compounds against murin leukemia P-388 cells, compound 1 was the strongest in inhibiting the growth of the cells.

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Cell Line, Tumor; Dipterocarpaceae; Drug Screening Assays, Antitumor; Leukemia P388; Magnetic Resonance Spectroscopy; Mice; Plant Bark; Solvents; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

Phytochemical investigation of the Australian lichen, Ramalina glaucescens resulted in the isolation of a new halogenated depside, 5-chlorosekikaic acid 5, together with (+)-usnic acid 1, sekikaic acid 2, atranorin 6 and parietin 7, the latter of which was isolated from the associated (co-occurring) lichen, X. parietina. Compound 5 is suspected to be an artifact of the isolation procedure. All structures were assigned using spectroscopic methods and mass spectrometry. In addition to the full characterization of 5, this report represents the first application of 2D NMR spectroscopy to complete the unequivocal chemical shift assignment for compounds 2 and 7. Compounds 1-2 and 5-7 all displayed varying degrees of antitumor activity (ranging from an IC50 of 15 microM to >44 microM) with compounds 1, 2 and 5 also displaying antibacterial properties. Of these, (+)-usnic acid 1 displayed the most significant antitumor and antibacterial activities.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Australia; Bacteria; Benzofurans; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Fungi; Leukemia P388; Lichens; Magnetic Resonance Spectroscopy; Mice; Microbial Sensitivity Tests; Spectrometry, Mass, Electrospray Ionization

Two new cyclopenta[b]benzofurans, aglaroxin A 1-O-acetate (2) and 3'-methoxyaglaroxin A 1-O-acetate (3), a new benzo[b]oxepine, 19,20-dehydroedulisone A (4), and five new cyclopenta[bc]benzopyrans, edulirin A (5), edulirin A 10-O-acetate (6), 19,20-dehydroedulirin A (7), isoedulirin A (8), and edulirin B (9), were isolated from the bark of Aglaia edulis, along with one known cyclopenta[b]benzofuran, aglaroxin A (1). Additionally, four new amides, aglamides A-D (10-13), as well as three known compounds, aglalactone, scopoletin, and 5-hydroxy-3,6,7,4'-tetramethoxyflavone, were isolated from the leaves and/or twigs of this species. The structures of the new compounds (2-13) were elucidated by interpretation of their spectroscopic data. All isolates obtained in this study were evaluated for cytotoxicity against both several human cancer cell lines (Lu1, LNCaP, and MCF-7) and a nontumorigenic (HUVEC) cell line. Among these isolates, the cyclopenta[b]benzofurans (1-3) exhibited potent in vitro cytotoxic activity (ED50 range 0.001 to 0.8 microg/mL). Aglaroxin A 1-O-acetate (2) was further evaluated in the in vivo P388 lymphocytic leukemia model, by intraperitoneal injection, but found to be inactive in this model.

Topics: Amides; Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Indonesia; Leukemia P388; Meliaceae; Mice; Models, Animal; Plant Bark; Plant Leaves; Plant Stems; Plants, Medicinal

Four new flavonoids, brosimacutins J-M (1 - 4), were isolated from the bark of Brosimum acutifolium Huber together with a known flavan, brosimine A (5). The structures of compounds 1-4 were elucidated by spectroscopic means. 27 constituents of this plant including compounds 1-5 were evaluated for their cytotoxic activity against murine leukemia P388 cells. Although no compounds tested had any reversal effect on vincristine resistance, brocimacutins J-M (1-4) were cytotoxic to vincristine-resistant P388 cells (IC50 4.4 - 19 microg/mL).

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Cell Line, Tumor; Flavonoids; Inhibitory Concentration 50; Leukemia P388; Mice; Moraceae; Phytotherapy; Plant Extracts

The first syntheses are reported for recently isolated drimanes 11, 12-epoxydrim-8,12-en-11-ol (2) and 11,12-diacetoxydrimane (3), from (-)-sclareol (1). Furthermore, two efficient new routes to the potent bioactive warburganal (4) starting also from 1 are described.

Topics: Animals; Antineoplastic Agents; Benzofurans; Diterpenes; Drug Screening Assays, Antitumor; Humans; Leukemia P388; Naphthalenes; Porifera; Sesquiterpenes; Structure-Activity Relationship; Tumor Cells, Cultured

Bioassay-directed fractionation of an EtOH extract of the moss Polytrichum pallidisetum (Polytrichaceae) led to the isolation of three novel benzonaphthoxanthenones, 1-O-methylohioensin B [6], 1-O-methyldihydroohioensin B [7] and 1,14-di-O-methyldihydroohioensin B [8], and two novel cinnamoyl bibenzyls, pallidisetin A [9] and pallidisetin B [10]. Their structures and relative stereochemistry were established by spectral analyses and chemical correlation. Compounds 6-10 exhibited cytotoxic activity against the human tumor cell lines RPMI-7951 melanoma and U-251 glioblastoma multiforme. These two types of compounds could hypothetically be derived from cinnamic acid and bibenzyls through different biogenetic pathways.

Topics: Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Cinnamates; Drug Screening Assays, Antitumor; Humans; Leukemia P388; Magnetic Resonance Spectroscopy; Mice; Molecular Conformation; Molecular Weight; Plants, Medicinal; Polycyclic Compounds; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Tumor Cells, Cultured; Xanthenes

Sequestration of calcium by mitochondria is an important mechanism to maintain normal intracellular calcium homeostasis. Anoxic or toxic damage to these organelles has been postulated to disrupt intracellular calcium compartmentalization, leading to cell death. The authors examined the potential relationship between mitochondrial dysfunction, altered calcium homeostasis, and irreversible injury in a model system of silica-induced toxicity to P388D1 cells. Exposure to toxic silica particles, but not to nontoxic latex heads, disrupted mitochondrial membrane potential, increased membrane-associated calcium, elevated free cytosolic calcium, and killed 50% to 60% of the cell population after 6 to 8 hours. To test whether disruption of the mitochondrial membrane potential was sufficient to cause irreversible injury, P388D1 cells were exposed to either the proton ionophore, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or to the mitochondrial inhibitor, antimycin A. Over 90% of the treated cells showed depolarization of the mitochondrial membrane as indicated by the fluorescent probe rhodamine 123. Carbonyl cyanide p-trifluoromethoxyphenylbydrazone also caused an elevation in free cytosolic calcium as monitored by fura-2. However, even after 6 hours of exposure to these proton ionophores or mitochondrial inhibitors, P388D1 cells did not show increased chlorotetracycline (CTC)-induced fluorescence or loss of viability. P388D1 cells exposed to silica have been shown previously to lose 80% of their adenosine triphosphate (ATP) content. The effect of reduced ATP levels on intracellular calcium homeostasis and viability was assessed by exposing P338D1 cells to FCCP in the presence of sodium azide and 2-deoxyglucose, which reduced ATP content by more than 90%. Under these conditions, none of the cells were killed, and only 5.5% showed increased CTC-induced fluorescence after 6 hours. These data indicate that disruption of the mitochondrial membrane potential, even in combination with reduced ATP content, is not sufficient to kill P388D1 cells.

Topics: Adenosine Triphosphate; Animals; Antimycin A; Benzofurans; Calcium; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Cell Survival; Chlortetracycline; Fluorescence; Fura-2; Homeostasis; Leukemia P388; Leukemia, Experimental; Macrophages; Membrane Potentials; Mice; Mitochondria; Silicon Dioxide

Topics: Animals; Antineoplastic Agents; Benzofurans; Drug Screening Assays, Antitumor; Humans; Indian Ocean; KB Cells; Leukemia P388; Mollusca; Plants, Medicinal; Polycyclic Aromatic Hydrocarbons; Xanthophylls; Zeaxanthins

Usnic acid, a lichen antibiotic, showed low-level activity in the Lewis lung carcinoma test system. In an effort to produce new agents of potential use in the treatment of lung cancer, derivatives of the natural product were synthesized and evaluated with a cytotoxicity assay. Structure--activity analysis of the cytotoxicity data indicated the importance of the lipophilicity and the beta-triketone moiety of usnic acid on cytotoxicity. No significant increases in survival of test animals over controls were shown by any of the synthetic compounds in the P388 leukemia or the Lewis lung carcinoma test systems.

Topics: Animals; Antineoplastic Agents; Benzofurans; In Vitro Techniques; Leukemia L1210; Leukemia P388; Lung Neoplasms; Mice; Neoplasms, Experimental; Solubility; Structure-Activity Relationship