Umbelliferone aminoalkyl derivatives as inhibitors of oxidosqualene cyclases from Saccharomyces cerevisiae, Trypanosoma cruzi, and Pneumocystis carinii

Lipids

Volumn 39, Issue 10, 2004, Pages 1007-1012

  Oliaro Bosso, Simonetta ^a   Viola, Franca ^a   Matsuda, Seiichi ^b   Cravotto, Giancarlo ^a   Tagliapietra, Silvia ^a   Balliano, Gianni ^a  

^a UNIVERSITY OF TURIN   (Italy)

^b RICE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DERIVATIVES; ENZYME INHIBITION; MICROORGANISMS; YEAST;

ANTIPARASITIC AGENTS; CELL HOMOGENATES; FLEXIBLE CHAINS; OXIDOSQUALENE CYCLASE (OSC);

ENZYMES;

ALKYL GROUP; OXIDOSQUALENE CYCLASE; SQUALENE DERIVATIVE; UMBELLIFERONE; UNCLASSIFIED DRUG;

ARTICLE; CELL FREE SYSTEM; ENZYME ACTIVITY; ISOTOPE LABELING; NONHUMAN; PNEUMOCYSTIS CARINII; SACCHAROMYCES CEREVISIAE; SPHEROPLAST; TRYPANOSOMA CRUZI;

ANIMALS; ANTIPARASITIC AGENTS; ENZYME INHIBITORS; INHIBITORY CONCENTRATION 50; INTRAMOLECULAR TRANSFERASES; KINETICS; PNEUMOCYSTIS CARINII; SACCHAROMYCES CEREVISIAE; STRUCTURE-ACTIVITY RELATIONSHIP; TRYPANOSOMA CRUZI; UMBELLIFERONES;

PNEUMOCYSTIS CARINII; SACCHAROMYCES; SACCHAROMYCES CEREVISIAE; TRYPANOSOMA; TRYPANOSOMA CRUZI;

EID: 11844279023     PISSN: 00244201     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11745-004-1323-2     Document Type: Article

References (28)

1. Nes, W.D. (1990) Control of Sterol Biosynthesis and Its Importance to Developmental Regulation and Evolution, Recent. Adv. Phytochem. 24, 283-327.
2. Abe, I., Rohmer, M., and Prestwich, G.D. (1993) Enzymatic Cyclization of Squalene and Oxidosqualene to Sterols and Triterpenes, Chem. Rev. 90, 2189-2206.
3. Wendt, K.U., Schulz, G.E., Corey, E.J., and Liu, D.R. (2000) Enzyme Mechanism for Polycyclic Triterpene Formation, Angew. Chem. Int. Ed. 2000 39, 2812-2833.
4. Mark, M., Müller, P., Maier, R., and Eisele, B. (1996) Effect of a Novel 2,3-Oxidosqualene Cyclase Inhibitor on the Regulation of Cholesterol Biosynthesis in HepG2 Cells, J. Lipid Res. 37, 148-158.
5. Morand, O.H., Aebi, J.D., Dehmlow, H., Ji, Y.H., Gains, N., Langsfeld, H., and Himber, J. (1997) Ro48-8071, a New 2,3-Oxidosqualene:Lanosterol Cyclase Inhibitor Lowering Plasma Cholesterol in Hamsters, Squirrel Monkeys, and Minipigs: Comparison to Simvastatin, J. Lipid Res. 38, 373-390.
6. Eisele, B., Budzinski, R., Müller, P., Maier, R., and Mark, M. (1997) Effects of a Novel 2,3-OSC Inhibitor on Cholesterol Biosynthesis and Lipid Metabolism in vivo, J. Lipid Res. 38, 564-575.
7. Brown, G.R., Hollinshead, D.M., Stokes, E.S.E., Clarke, D.S., Eakin, M.A., Foubister, A.J., Glossop, S.C., Griffiths, D., Johnson, M.C., McTaggart, F., Mirrlees, D.J., Smith, G.J., and Wood, R. (1999) Quinuclidine Inhibitors of 2,3-Oxidosqualene Cyclase-Lanosterol Synthase: Optimization from Lipid Profiles, J. Med. Chem. 42, 1306-1311.
8. Dehlmlow, H., Aebi, J.D., Jolidon, S., Ji, Y.-H., von der Mark, E.M., Himber, J., and Morand, O.H. (2003) Synthesis and Structural Activity Studies of Novel Orally Active non-Terpenoic 2,3-Oxidosqualene Cyclase Inhibitors, J. Med. Chem. 46, 3354-3370.
9. Buckner, F.S., Griffin, J.H, Wilson, A.J., and van Voorhis, W.C. (2001) Potent anti-Trypanosoma cruzi Activities of OSC Inhibitors, Antimicrob. Agents Chemother. 45, 1210-1215.
10. Hinshaw, J.C., Suh, D.-Y., Garnier, P., Buckner, F.S., Eastman, R.T., Matsuda, S.P.T., Joubert, B.M., Coppens, I., Joiner, K.A., Merali, S., Nash, T.E., and Prestwich, G.D. (2003) OSC Inhibitors as Antimicrobial Agents. J. Med. Chem. 46, 4240-4243.
11. Cravotto, G., Balliano, G., Chimichi, S., Robaldo, B., Oliaro-Bosso, S., and Boccalini, M. (2004) Farnesyloxy coumarins, a New Class of Squalene-Hopene Cyclase Inhibitors, Bioorg. Med. Chem. Lett. 14, 1931-1934.
12. Cravotto, G., Balliano, G., Tagliapietra, S., Oliaro-Bosso, S., and Nano, G.M. (2004) Novel Squalene-Hopene Cyclase Inhibitors Derived from Hydroxycoumarins and Hydroxyacetophenones, Chem. Pharm. Bull. 52, 1171-1174.
13. Cravotto, G., Balliano, G., Tagliapietra, S., Palmisano, G., and Penoni, A. (2004) Umbelliferone Aminoalkyl Derivatives, a New Class of Squalene-Hopene Cyclase Inhibitors, Eur. J. Med. Chem. 39, 917-924.
14. Wendt, K.U., Poralla, K., and Schulz, G.E. (1997) Structure and Function of Squalene Cyclase, Science 277, 1811-1815.
15. Wendt, K.U., Lenhart, A., and Schulz, G.E. (1999) The Structure of the Membrane Protein Squalene-Hopene Cyclase at 2 Å Resolution, J. Mol. Biol. 286, 175-187.
16. Lenhart, A., Reinert, D.J., Aebi, J.D., Dehmlow, H., Morand, O.H., and Schulz, G.E. (2003) Binding Structures and Potencies of OSC Inhibitors with the Homologous Squalene-Hopene Cyclase, J. Med. Chem. 46, 2083-2092.
17. Joubert, B.M., Buckner, F.S., and Matsuda, S.P.T. (2001) Trypanosome and Animal Lanosterol Synthases Use Different Catalytic Motif, Org. Lett. 3, 1957-1960.
18. Milla, P., Viola, F., Oliaro-Bosso, S., Rocco, F., Cattel, L., Joubert, B.M., LeClair, R.J., Matsuda, S.P.T., and Balliano, G. (2002) Subcellular Localization of OxidoSqualene Cyclases from Arabidopsis thaliana, Trypanosoma cruzi, and Pneumocystis carinii Expressed in Yeast, Lipids 37, 1171-1176.
19. Ceruti, M., Balliano, G., Viola, F., Cattel, L., Gerst, N., and Schuber, F. (1987) Synthesis and Biological Activity of Azasqualenes, Bis-azasqualenes and Derivatives, Eur. J. Med. Chem. 22,199-208.
20. Popják, G. (1969) Methods in Enzymology, Steroids and Terpenoids (Clayton, R.B., ed.), Vol. 15, pp. 438-443, Academic Press, New York.
21. Field, R.B., Holmlund, C.E., and Whittaker, N.F. (1979) The Effect of the Hypocholesteremic Compound 3β-(β-dimethy-laminoethoxy)-Androst-en17- one on the Sterol and Steryl Ester Composizion of Saccharomyces cerevisiae, Lipids 14, 741-747.
22. Servouse, M., and Karst, F. (1986) Regulation of Early Enzyme of Ergosterol Biosynthesis in Saccharomyces cerevisiae, Biochem. J. 240, 541-547.
23. Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with the Polin Phenol Reagent, J. Biol. Chem. 193, 265-275.
24. Milla, P., Athenstaedt, K., Viola, F., Oliaro-Bosso, S., Kohlwein, S.E., Daum, G., and Balliano. G. (2002) Yeast Oxidosqualene Cyclase (Erg7p) Is a Major Component of Lipid Particles, J. Biol. Chem. 277, 2406-2412.
25. Binet, J., Thomas, D., Benmbarek, A., de Fornel, D., and Renaut, P. (2002) Structure-Activity Relationships of New Inhibitors of Mammalian 2,3-Oxidosqualene Cyclase Designed from Isoquinoline Derivatives, Chem. Pharm. Bull. 50, 316-329.
26. Schulz-Gasch, T., and Sthal, M. (2003) Mechanistic Insights into Oxidosqualene Cyclizations Through Homology Modeling, J. Compul. Chem. 24, 741-753.
27. Reinert, D.J., Balliano, G., and Schulz, G.E. (2004) Conversion of Squalene to the Pentacarbocyclic Hopene, Chem. Biol. 11, 121-126.
28. Thoma, R., Schulz-Gasch, T., D'Arcy, B., Benz, J., Aebi, J., Dehmlow, H., Hennig, M., Stihle, M., and Ruf, A. (2004) Insight into Steroid Scaffold Formation from the Structure of Human Oxidosqualene Cyclase, Nature 432, 118-122.