ABSTRACT
The crude extract of the broth of Aspergillus ochraceus was found to inhibit the final stage of polyprotein processing during hepatitis C virus replication. Bioassay-guided fractionation led to the isolation of the known compound mellein as the active component of the extract. Also isolated were circumdatin F and a new alkaloid, circumdatin G. The structure of circumdatin G was determined by spectroscopic analysis.
Subject(s)
Alkaloids/isolation & purification , Antiviral Agents/isolation & purification , Aspergillus ochraceus/chemistry , Ochratoxins/isolation & purification , Alkaloids/chemistry , Alkaloids/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fermentation , Hepacivirus/drug effects , Hepacivirus/enzymology , Isocoumarins , Magnetic Resonance Spectroscopy , Ochratoxins/chemistry , Ochratoxins/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/isolation & purification , Protease Inhibitors/pharmacology , Virus Replication/drug effectsABSTRACT
Two novel human cytomegalovirus protease inhibitors, cytonic acids A (1) and B (2), have been isolated from the solid-state fermentation of the endophytic fungi Cytonaema sp. Their structures as p-tridepside isomers were elucidated by MS and NMR methods.
Subject(s)
Benzoates/isolation & purification , Mitosporic Fungi/metabolism , Protease Inhibitors/isolation & purification , Serine Endopeptidases/metabolism , Benzoates/pharmacology , Chromatography, High Pressure Liquid , Chromatography, Liquid , Fermentation , Magnetic Resonance Spectroscopy , Mass Spectrometry , Protease Inhibitors/pharmacologyABSTRACT
Two novel spirosesquiterpene aldehydes, corallidictyals A [1] and B [2], were isolated as a mixture from the marine sponge Aka (= Siphonodictyon) coralliphagum, and their structures were determined by detailed spectroscopic methods. These compounds were identified in a screen for inhibitors of protein kinase C.
Subject(s)
Cell Division/drug effects , Porifera , Protein Kinase C/antagonists & inhibitors , Sesquiterpenes/isolation & purification , Spiro Compounds/isolation & purification , Animals , Chlorocebus aethiops , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Models, Molecular , Molecular Conformation , Molecular Structure , Recombinant Proteins/antagonists & inhibitors , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Spiro Compounds/pharmacology , Structure-Activity Relationship , Vero CellsABSTRACT
Research into marine natural products is evolving from an empirical search for antimicrobial and cytotoxic compounds into a more mechanistic approach to the discovery of enzyme inhibitors and receptor antagonists with therapeutic potential. Several marine natural products have entered pharmaceutical development and others are making significant contributions to our understanding of cellular processes at the biochemical level.
Subject(s)
Biological Products/isolation & purification , Marine Biology , Animals , Anti-Infective Agents/isolation & purification , Antineoplastic Agents/isolation & purification , Biotechnology , Enzyme Inhibitors/isolation & purification , Immunosuppressive Agents/isolation & purification , Receptors, Cell Surface/antagonists & inhibitorsABSTRACT
A sesquiterpene thioacetate, 15-acetylthioxy-furodysinin (SK&F 105900) has been isolated from the sponge Dysidea SP. This compound can bind specifically to the human peripheral blood polymorphonuclear leukocyte (PMN) and to the differentiated human monocytic leukemic U-937 cell membrane leukotriene B4 (LTB4) receptors with high-affinity. This compound can also promote a concentration-dependent chemotaxis in PMNs and an intracellular calcium mobilization in U-937 cells that can be blocked by the LTB4 receptor antagonist, LY-223982. Furthermore, the calcium mobilization induced by SK&F 105900 can specifically cross-desensitize with the LTB4-induced calcium mobilization. These observations indicate that SK&F 105900 is a novel and specific high-affinity agonist that can bind to the LTB4 receptors and activate the receptor-mediated signal transduction processes in human PMN and U-937 cells.
Subject(s)
Receptors, Immunologic/metabolism , Sesquiterpenes/metabolism , Animals , Calcium/metabolism , Chemotaxis, Leukocyte , Humans , Leukemia, Myeloid , Leukotriene B4/metabolism , Leukotriene B4/pharmacology , Neutrophils/drug effects , Neutrophils/metabolism , Receptors, Leukotriene B4 , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Tumor Cells, CulturedABSTRACT
Nine triterpenes with antiviral activity against Herpes simplex virus types I and II in vitro were isolated from dammar resin. Each compound caused a significant reduction in viral cytopathic effect when Vero cells were exposed continuously to 1-10 micrograms/ml of compound for 48 h after viral challenge. The triterpenes were identified as dammaradienol [1], dammarenediol-II [2], hydroxydammarenone-I [3], ursonic acid [5], hydroxyhopanone [11], dammarenolic acid [15], shoreic acid [16], eichlerianic acid [17], and a novel compound, hydroxyoleanonic lactone [7], on the basis of their chromatographic, spectroscopic, and physical properties.
