Synthesis and inhibition studies of sulfur-substituted squalene oxide analogues as mechanism-based inhibitors of 2,3-oxidosqualene-lanosterol cyclase

Journal of Medicinal Chemistry

Volumn 40, Issue 2, 1997, Pages 201-209

  Stach, Dirk ^a,e   Zheng, Yi Feng ^a,d   Perez, Alice L ^a,f   Oehlschlager, Allan C ^a   Abe, Ikuro ^b,d   Prestwich, Glenn D ^b,d   Hartman, Peter G ^c  

^a SIMON FRASER UNIVERSITY   (Canada)

^b STONY BROOK UNIVERSITY   (United States)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

^d UNIVERSITY OF UTAH   (United States)

^e Brillux   (Germany)

^f UNIVERSIDAD DE COSTA RICA   (Costa Rica)

Author keywords

[No Author keywords available]

Indexed keywords

15,16 EPOXY 3,8,12,16 TETRAMETHYLHEPTADECATRIENYL 1',5' DIMETHYL 4' HEXENYLSULFIDE; LANOSTEROL SYNTHASE INHIBITOR; SQUALENE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CANDIDA ALBICANS; DRUG CONFORMATION; DRUG POTENCY; ENZYME INHIBITION; ENZYME MECHANISM; INHIBITION KINETICS; STRUCTURE ANALYSIS;

ANIMALS; ENZYME INHIBITORS; INTRAMOLECULAR TRANSFERASES; ISOMERASES; KINETICS; LIVER; MOLECULAR CONFORMATION; RATS; SQUALENE; SULFUR; SWINE;

EID: 15644369146     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960483a     Document Type: Article

References (63)

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10. For recent work on cloning and functional expression of lanosterol synthase from various organisms, see: (a) Buntel, C. J.; Griffin, J. H. Nucleotide and Deduced Amino Acid Sequences of the Oxidosqualene Cyclase from Candida albicans. J. Am. Chem. Soc. 1992, 114, 9711-9713 (C. albicans). (b) Corey, E. J.; Matsuda, S. P. T.; Baker, C. H.; Ting, A. Y.; Cheng, H. Molecular Cloning of a Schizosaccharomyces pombe cDNA Encoding Lanoterol Synthase and Investigation of Conserved Tryptophan Residues. Biochem. Biophys. Res. Commun. 1996, 219, 327-331 (Schizosaccharomyces pombe). (c) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Molecular Cloning, Characterization, and Overexpression of ERG7, the Saccharomyces cerevisiae Gene Encoding Lanosterol Synthase. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2211-2215 (Saccharomyces cerevisiae). (d) Shi, Z.; Buntel, C. J.; Griffin, J. H. Isolation and Characterization of the Gene Encoding 2,3-Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7370-7374 (S. cerevisiae). (e) Abe, I.; Prestwich, G. D. Molecular Cloning, Characterization, and Functional Expression of Rat Oxidosqualene Cyclase. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 9274-9278 (Rattus norvegicus). (f) Baker, C. H.; Matsuda, S. P. T.; Liu, D. R.; Corey, E. J. Molecular Cloning of the Human Gene Encoding Lanosterol Synthase from a Liver cDNA Library. Biochem. Biophys. Res. Commun. 1995, 273, 154-160 (Homo sapiens). (g) Kusano, M.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Rat 2,3-Oxidosqualene: Lanosterol Cyclase. Biol. Pharm. Bull. 1995, 18, 195-197 (R. norvegicus). (h) Sung, C. H.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Human Lanosterol Synthase. Biol. Pharm. Bull. 1995, 18, 1459-1461 (H. sapiens).
11. For recent work on cloning and functional expression of lanosterol synthase from various organisms, see: (a) Buntel, C. J.; Griffin, J. H. Nucleotide and Deduced Amino Acid Sequences of the Oxidosqualene Cyclase from Candida albicans. J. Am. Chem. Soc. 1992, 114, 9711-9713 (C. albicans). (b) Corey, E. J.; Matsuda, S. P. T.; Baker, C. H.; Ting, A. Y.; Cheng, H. Molecular Cloning of a Schizosaccharomyces pombe cDNA Encoding Lanoterol Synthase and Investigation of Conserved Tryptophan Residues. Biochem. Biophys. Res. Commun. 1996, 219, 327-331 (Schizosaccharomyces pombe). (c) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Molecular Cloning, Characterization, and Overexpression of ERG7, the Saccharomyces cerevisiae Gene Encoding Lanosterol Synthase. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2211-2215 (Saccharomyces cerevisiae). (d) Shi, Z.; Buntel, C. J.; Griffin, J. H. Isolation and Characterization of the Gene Encoding 2,3-Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7370-7374 (S. cerevisiae). (e) Abe, I.; Prestwich, G. D. Molecular Cloning, Characterization, and Functional Expression of Rat Oxidosqualene Cyclase. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 9274-9278 (Rattus norvegicus). (f) Baker, C. H.; Matsuda, S. P. T.; Liu, D. R.; Corey, E. J. Molecular Cloning of the Human Gene Encoding Lanosterol Synthase from a Liver cDNA Library. Biochem. Biophys. Res. Commun. 1995, 273, 154-160 (Homo sapiens). (g) Kusano, M.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Rat 2,3-Oxidosqualene: Lanosterol Cyclase. Biol. Pharm. Bull. 1995, 18, 195-197 (R. norvegicus). (h) Sung, C. H.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Human Lanosterol Synthase. Biol. Pharm. Bull. 1995, 18, 1459-1461 (H. sapiens).
12. For recent work on cloning and functional expression of lanosterol synthase from various organisms, see: (a) Buntel, C. J.; Griffin, J. H. Nucleotide and Deduced Amino Acid Sequences of the Oxidosqualene Cyclase from Candida albicans. J. Am. Chem. Soc. 1992, 114, 9711-9713 (C. albicans). (b) Corey, E. J.; Matsuda, S. P. T.; Baker, C. H.; Ting, A. Y.; Cheng, H. Molecular Cloning of a Schizosaccharomyces pombe cDNA Encoding Lanoterol Synthase and Investigation of Conserved Tryptophan Residues. Biochem. Biophys. Res. Commun. 1996, 219, 327-331 (Schizosaccharomyces pombe). (c) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Molecular Cloning, Characterization, and Overexpression of ERG7, the Saccharomyces cerevisiae Gene Encoding Lanosterol Synthase. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2211-2215 (Saccharomyces cerevisiae). (d) Shi, Z.; Buntel, C. J.; Griffin, J. H. Isolation and Characterization of the Gene Encoding 2,3-Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7370-7374 (S. cerevisiae). (e) Abe, I.; Prestwich, G. D. Molecular Cloning, Characterization, and Functional Expression of Rat Oxidosqualene Cyclase. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 9274-9278 (Rattus norvegicus). (f) Baker, C. H.; Matsuda, S. P. T.; Liu, D. R.; Corey, E. J. Molecular Cloning of the Human Gene Encoding Lanosterol Synthase from a Liver cDNA Library. Biochem. Biophys. Res. Commun. 1995, 273, 154-160 (Homo sapiens). (g) Kusano, M.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Rat 2,3-Oxidosqualene: Lanosterol Cyclase. Biol. Pharm. Bull. 1995, 18, 195-197 (R. norvegicus). (h) Sung, C. H.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Human Lanosterol Synthase. Biol. Pharm. Bull. 1995, 18, 1459-1461 (H. sapiens).
13. For recent work on cloning and functional expression of lanosterol synthase from various organisms, see: (a) Buntel, C. J.; Griffin, J. H. Nucleotide and Deduced Amino Acid Sequences of the Oxidosqualene Cyclase from Candida albicans. J. Am. Chem. Soc. 1992, 114, 9711-9713 (C. albicans). (b) Corey, E. J.; Matsuda, S. P. T.; Baker, C. H.; Ting, A. Y.; Cheng, H. Molecular Cloning of a Schizosaccharomyces pombe cDNA Encoding Lanoterol Synthase and Investigation of Conserved Tryptophan Residues. Biochem. Biophys. Res. Commun. 1996, 219, 327-331 (Schizosaccharomyces pombe). (c) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Molecular Cloning, Characterization, and Overexpression of ERG7, the Saccharomyces cerevisiae Gene Encoding Lanosterol Synthase. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2211-2215 (Saccharomyces cerevisiae). (d) Shi, Z.; Buntel, C. J.; Griffin, J. H. Isolation and Characterization of the Gene Encoding 2,3-Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7370-7374 (S. cerevisiae). (e) Abe, I.; Prestwich, G. D. Molecular Cloning, Characterization, and Functional Expression of Rat Oxidosqualene Cyclase. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 9274-9278 (Rattus norvegicus). (f) Baker, C. H.; Matsuda, S. P. T.; Liu, D. R.; Corey, E. J. Molecular Cloning of the Human Gene Encoding Lanosterol Synthase from a Liver cDNA Library. Biochem. Biophys. Res. Commun. 1995, 273, 154-160 (Homo sapiens). (g) Kusano, M.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Rat 2,3-Oxidosqualene: Lanosterol Cyclase. Biol. Pharm. Bull. 1995, 18, 195-197 (R. norvegicus). (h) Sung, C. H.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Human Lanosterol Synthase. Biol. Pharm. Bull. 1995, 18, 1459-1461 (H. sapiens).
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15. For recent work on cloning and functional expression of lanosterol synthase from various organisms, see: (a) Buntel, C. J.; Griffin, J. H. Nucleotide and Deduced Amino Acid Sequences of the Oxidosqualene Cyclase from Candida albicans. J. Am. Chem. Soc. 1992, 114, 9711-9713 (C. albicans). (b) Corey, E. J.; Matsuda, S. P. T.; Baker, C. H.; Ting, A. Y.; Cheng, H. Molecular Cloning of a Schizosaccharomyces pombe cDNA Encoding Lanoterol Synthase and Investigation of Conserved Tryptophan Residues. Biochem. Biophys. Res. Commun. 1996, 219, 327-331 (Schizosaccharomyces pombe). (c) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Molecular Cloning, Characterization, and Overexpression of ERG7, the Saccharomyces cerevisiae Gene Encoding Lanosterol Synthase. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 2211-2215 (Saccharomyces cerevisiae). (d) Shi, Z.; Buntel, C. J.; Griffin, J. H. Isolation and Characterization of the Gene Encoding 2,3-Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7370-7374 (S. cerevisiae). (e) Abe, I.; Prestwich, G. D. Molecular Cloning, Characterization, and Functional Expression of Rat Oxidosqualene Cyclase. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 9274-9278 (Rattus norvegicus). (f) Baker, C. H.; Matsuda, S. P. T.; Liu, D. R.; Corey, E. J. Molecular Cloning of the Human Gene Encoding Lanosterol Synthase from a Liver cDNA Library. Biochem. Biophys. Res. Commun. 1995, 273, 154-160 (Homo sapiens). (g) Kusano, M.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Rat 2,3-Oxidosqualene: Lanosterol Cyclase. Biol. Pharm. Bull. 1995, 18, 195-197 (R. norvegicus). (h) Sung, C. H.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Molecular Cloning of cDNA Encoding Human Lanosterol Synthase. Biol. Pharm. Bull. 1995, 18, 1459-1461 (H. sapiens).
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44. 50 values for C. albicans were not further examined.
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