Subject(s)
Alkaloids/chemical synthesis , Alkaloids/pharmacology , Sulfides/chemistry , Urochordata/chemistry , Alkaloids/chemistry , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Division/drug effects , Mice , Microbial Sensitivity Tests , Molecular Structure , Spectrum Analysis , Stereoisomerism , Tumor Cells, Cultured/drug effectsABSTRACT
From the New Zealand ascidian, Lissoclinum notti a new natural product, N2,N2,7-trimethylguanine (1) has been isolated. The structure of 1 was elucidated by analysis of spectroscopic data.
Subject(s)
Anti-Infective Agents/isolation & purification , Antineoplastic Agents/isolation & purification , Guanine/isolation & purification , Urochordata/chemistry , Animals , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bacillus subtilis/drug effects , Breast Neoplasms , CDC2 Protein Kinase/metabolism , CDC28 Protein Kinase, S cerevisiae/metabolism , Candida albicans/drug effects , Cell Cycle/drug effects , Chromatography, High Pressure Liquid , Drug Screening Assays, Antitumor , Escherichia coli/drug effects , Female , Guanine/analogs & derivatives , Guanine/chemistry , Guanine/pharmacology , Inhibitory Concentration 50 , Leukemia P388 , Lung Neoplasms , Mass Spectrometry , Mice , Molecular Structure , Nervous System Neoplasms , New Zealand , RNA/physiology , Spectrophotometry, Infrared , Spectroscopy, Fourier Transform Infrared , Trichophyton/drug effects , Tumor Cells, Cultured/drug effectsABSTRACT
The new purine 1,3,7-trimethylisoguanine (1) has been isolated from the ascidian Pseudodistoma cereum. The structure of 1 was elucidated by analysis of NMR spectroscopic and mass spectrometric data and by comparison with the regioisomeric purine 1,3,7-trimethylguanine (2).
Subject(s)
Guanine/analogs & derivatives , Urochordata/chemistry , Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Gas Chromatography-Mass Spectrometry , Guanine/chemistry , Guanine/isolation & purification , Magnetic Resonance Spectroscopy , New Zealand , Spectrophotometry, UltravioletABSTRACT
The title compounds, C16H13NO2S, (I), and C21H15NO2S, (II), have similar molecular structures that differ only in the side groups attached to the S atom. The crystal packing is dominated by pi-pi stacking interactions, involving acridinedione-acridinedione overlap in (I) and both acridinedione-acridinedione and acridinedione-tolyl overlap in (II).
Subject(s)
Acridines/chemistry , Crystallography, X-Ray , Models, MolecularABSTRACT
The known 2-aminoimidazole alkaloid naamidine A (1) was isolated from a Fijian Leucetta sp. sponge as an inhibitor of the epidermal growth factor (EGF) receptor. The compound exhibited potent ability to inhibit the EGF signaling pathway and is more specific for the EGF-mediated mitogenic response than for the insulin-mediated mitogenic response. Evaluation in an A431 xenograft tumor model in athymic mice indicated that naamidine A exhibited at least 85% growth inhibition at the maximal tolerated dose of 25 mg/kg. Preliminary mechanism of action studies indicate that the alkaloid fails to inhibit the binding of EGF to the receptor and has no effect on the catalytic activity of purified c-src tyrosine kinase.
Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents/pharmacology , ErbB Receptors/antagonists & inhibitors , Imidazoles/pharmacology , 3T3 Cells , Alkaloids/isolation & purification , Animals , Antineoplastic Agents/isolation & purification , CSK Tyrosine-Protein Kinase , Carcinoma, Squamous Cell/pathology , Cell Division/drug effects , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Epidermal Growth Factor/metabolism , ErbB Receptors/metabolism , Imidazoles/isolation & purification , Mice , Mice, Nude , Neoplasm Transplantation , Porifera/chemistry , Protein-Tyrosine Kinases/antagonists & inhibitors , Transplantation, Heterologous , src-Family KinasesABSTRACT
From the ascidian Cnemidocarpa bicornuta, 2-(3'-bromo-4'-hydroxyphenol)ethanamine (3'-bromotyramine) (1) has been isolated along with the previously reported sponge metabolite, 1,3-dimethylisoguanine. The structure of 1 was confirmed by synthesis.
Subject(s)
Antineoplastic Agents/pharmacology , Tyramine/analogs & derivatives , Urochordata/chemistry , Animals , Antineoplastic Agents/isolation & purification , Bacteria/drug effects , Candida albicans , Chromatography, High Pressure Liquid , Leukemia P388/drug therapy , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Microbial Sensitivity Tests , New Zealand , Rats , Spectrophotometry, Ultraviolet , Tyramine/isolation & purification , Tyramine/pharmacologyABSTRACT
Xenovulene A, a novel inhibitor of benzodiazepine binding to the GABA-benzodiazepine receptor is produced by submerged fermentation of Acremonium strictum. It was isolated from the mycelium by solvent extraction and purified by chromatography on Sephadex LH-20 and octadecyl silica. The structure of xenovulene A was determined to be a novel oxygenated sesquiterpene containing a humulene moiety by interpretation of various spectroscopic data, especially from 2D NMR experiments. Xenovulene A inhibited binding of the benzodiazepine, flunitrazepam, with an IC50 of 40 nM in an in vitro assay using bovine synaptosome membrane preparations.
Subject(s)
Receptors, GABA/drug effects , Sesquiterpenes/isolation & purification , Acremonium/metabolism , Animals , Cattle , Fermentation , Flunitrazepam/metabolism , Molecular Structure , Receptors, GABA/metabolism , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
The makaluvamines were isolated from a sponge of the genus Zyzzya by following bioactivity against the human colon carcinoma cell line, HCT 116. These compounds have considerable cytotoxic activity. The makaluvamines appear to be acting through inhibition of DNA topoisomerase II. The compounds show enhanced toxicity toward a topoisomerase II-cleavable complex-sensitive cell line, they inhibit topoisomerase II decatenation of kinetoplast DNA in vitro. Makaluvamine C was shown to produce protein-linked DNA double-strand breaks, and makaluvamine A produced DNA double-strand breaks by neutral filter elution in a dose-dependent fashion similar to 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA). The makaluvamines also increased the life span of nude mice bearing solid tumors of human ovarian cancer cells.
Subject(s)
Antineoplastic Agents/pharmacology , Porifera/chemistry , Pyrroles/pharmacology , Quinones/pharmacology , Topoisomerase II Inhibitors , Animals , CHO Cells , Colonic Neoplasms/drug therapy , Cricetinae , Drug Screening Assays, Antitumor , Female , Humans , Leukemia, Experimental/drug therapy , Mice , Mice, Inbred BALB C , Mice, Inbred Strains , Mice, Nude , Neoplasm Transplantation , Ovarian Neoplasms/drug therapy , Pyrroles/isolation & purification , Quinones/isolation & purification , Tumor Cells, CulturedABSTRACT
The new, cytotoxic dibromotyrosine-derived metabolite psammaplysin C [3], in addition to the two known psammaplysins A [1] and B [2], was isolated from the marine sponge Druinella purpurea. All three compounds were found to possess moderate in vitro cytotoxicity towards the human colon tumor cell-line HCT116.