ABSTRACT
In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.
Subject(s)
Antifungal Agents/isolation & purification , Enzyme Inhibitors/isolation & purification , Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors , Pyrans/isolation & purification , Stachybotrys/metabolism , Animals , Antifungal Agents/pharmacology , Enzyme Inhibitors/pharmacology , Fermentation , Hepatocytes , Humans , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Pyrans/pharmacology , Rats , Stachybotrys/chemistry , Stachybotrys/classificationABSTRACT
The squalene synthase inhibitor bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260, and its structure was determined on the basis of spectroscopic methods including detailed 2D NMR analyses. The structures of bisabosquals B, C and D isolated from Stachybotrys ruwenzoriensis RF-6853 were determined by spectroscopic methods and chemical reactions. The absolute stereochemistry of bisabosquals A, B and D was determined by X-ray crystallographic analysis. They have novel cis-fused tetracyclic structures with a bisabolane-type sesquiterpene and phenol moieties.
Subject(s)
Enzyme Inhibitors/chemistry , Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors , Pyrans/isolation & purification , Stachybotrys/chemistry , Crystallography, X-Ray , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , Molecular Weight , Optical Rotation , Pyrans/pharmacology , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , StereoisomerismSubject(s)
Aspergillus/metabolism , Biphenyl Compounds/metabolism , Biphenyl Compounds/pharmacology , Immunosuppressive Agents/metabolism , Immunosuppressive Agents/pharmacology , Terphenyl Compounds/metabolism , Terphenyl Compounds/pharmacology , Animals , Biphenyl Compounds/chemistry , Chemical Phenomena , Chemistry, Physical , Concanavalin A/pharmacology , Crystallography, X-Ray , Immunosuppressive Agents/chemistry , In Vitro Techniques , Lipopolysaccharides/pharmacology , Lymphocyte Activation/drug effects , Lymphocytes/drug effects , Lymphocytes/immunology , Magnetic Resonance Spectroscopy , Mice , Models, Molecular , Molecular Conformation , Molecular Structure , Terphenyl Compounds/chemistryABSTRACT
New inhibitors of aldose reductase, designated salfredins A3, A4, A7, C1, C2, C3 and B11, were isolated from the fermentation broth of Crucibulum sp. RF-3817 by successive purification procedures of solvent extraction, silica gel column chromatographies and reverse-phase HPLC. Their structures were established by spectroscopic methods, including UV, SI-MS and NMR. The structures of salfredins A4 and B11 were confirmed by X-ray crystallographic analysis.
