Bisabosquals, novel squalene synthase inhibitors. I. Taxonomy, fermentation, isolation and biological activities.

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.

[1]  W. Agnew,et al.  Squalene synthetase , 2004, Molecular and Cellular Biochemistry.

[2]  Y. Kawamura,et al.  Bisabosquals, novel squalene synthase inhibitors. II. Physico-chemical properties and structure elucidation. , 2001, The Journal of antibiotics.

[3]  Hironobu Nakayama,et al.  Depletion of the Squalene Synthase (ERG9) Gene Does Not Impair Growth of Candida glabrata in Mice , 2000, Antimicrobial Agents and Chemotherapy.

[4]  K. Hasumi,et al.  Isolation of SMTP-3, 4, 5 and -6, novel analogs of staplabin, and their effects on plasminogen activation and fibrinolysis. , 1998, The Journal of antibiotics.

[5]  M. Endo,et al.  Microencapsulated Osmium Tetraoxide. A New Recoverable and Reusable Polymer-Supported Osmium Catalyst for Dihydroxylation of Olefins. , 1998, The Journal of organic chemistry.

[6]  K. Mizoue,et al.  Stachybotrin C and parvisporin, novel neuritogenic compounds. II. Structure determination. , 1997, The Journal of antibiotics.

[7]  K. Hasumi,et al.  SMTP-1 and -2, novel analogs of staplabin produced by Stachybotrys microspora IFO30018. , 1997, The Journal of antibiotics.

[8]  K. Hasumi,et al.  Staplabin, a novel fungal triprenyl phenol which stimulates the binding of plasminogen to fibrin and U937 cells. , 1996, The Journal of antibiotics.

[9]  K. Shin‐ya,et al.  Stachybocins, novel endothelin receptor antagonists, produced by Stachybotrys sp. M6222. II. Structure determination of stachybocins A, B and C. , 1995, The Journal of antibiotics.

[10]  K. Hasumi,et al.  Modulation of the plasma cholesteryl ester transfer by stachybotramide. , 1995, Biochimica et biophysica acta.

[11]  Kazuo Watanabe,et al.  Isolation, characterization and biological activities of novel triprenyl phenols as pancreatic cholesterol esterase inhibitors produced by Stachybotrys sp. F-1839. , 1995, The Journal of antibiotics.

[12]  T. Nishino,et al.  Cloning, expression, and characterization of cDNAs encoding Arabidopsis thaliana squalene synthase. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Payne,et al.  Semi‐Synthetic Squalestatins: Squalene Synthase Inhibition and Antifungal Activity. The SAR of C6 and C7 Modifications. , 1994 .

[14]  S. Mizuno,et al.  Mer-NF5003B, E and F, novel sesquiterpenoids as avian myeloblastosis virus protease inhibitors produced by Stachybotrys sp. , 1994, The Journal of antibiotics.

[15]  F. Karst,et al.  Cloning, expression and characterisation of the cDNA encoding human hepatic squalene synthase, and its relationship to phytoene synthase. , 1993, Gene.

[16]  J. Payne,et al.  Semi-synthetic qualestatins: Squalene synthase inhibition and antifungal activity. The SAR of C6 and C7 modifications , 1993 .

[17]  W. Ayer,et al.  Secondary metabolites of the aspen fungus Stachybotrys cylindrospora , 1993 .

[18]  C. Shearer,et al.  Stachybotrins A and B: novel bioactive metabolites from a brackish water isolate of the fungus Stachybotrys sp , 1992 .

[19]  R. Tait Development of a radiometric spot-wash assay for squalene synthase. , 1992, Analytical biochemistry.

[20]  G. Robinson,et al.  Molecular cloning and characterization of the yeast gene for squalene synthetase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Matsushima Matsushima Mycological Memoirs No. 3 , 1984 .

[22]  W. Miyazaki,et al.  Structure of K-76, a complement inhibitor produced by Stachybotrys complementi nov. Sp. K-76 , 1979 .

[23]  M. B. Ellis,et al.  More Dematiaceous Hyphomycetes , 1976 .