Lanosterol analogs: Dual-action inhibitors of cholesterol biosynthesis

Critical Reviews in Biochemistry and Molecular Biology

Volumn 34, Issue 2, 1999, Pages 123-140

  Frye, Leah L ^a   Leonard, Deborah A ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXY 3 METHYLGLUTARYL COENZYME A; CARBON 14; CHOLESTEROL; CYTOCHROME P450 ISOENZYME; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; KETONE DERIVATIVE; LANOSTEROL DERIVATIVE; LOW DENSITY LIPOPROTEIN RECEPTOR; MEVALONIC ACID; OXIME DERIVATIVE; STEROL 14ALPHA DEMETHYLASE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; CHO CELL; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG STRUCTURE; GENE EXPRESSION; ISCHEMIC HEART DISEASE; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL; RAT; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; ANTICHOLESTEREMIC AGENTS; CHO CELLS; CORONARY DISEASE; CRICETINAE; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; HYDROXYMETHYLGLUTARYL COA REDUCTASES; INHIBITORY CONCENTRATION 50; KETONES; LANOSTEROL; MICROSOMES, LIVER; MODELS, BIOLOGICAL; MODELS, CHEMICAL; OXIDOREDUCTASES; OXIMES; RATS; RECEPTORS, LDL; RNA PROCESSING, POST-TRANSCRIPTIONAL; TIME FACTORS;

EID: 0032940786     PISSN: 10409238     EISSN: None     Source Type: Journal    
DOI: 10.1080/10409239991209246     Document Type: Review

References (52)

1. Blankenhorn, D. H., Nessim, S. A., Johnson, R. L., Sanmarco, M. E., Azen, S. P., and Cashin-Hempill, L., Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous by-pass grafts, JAMA, 257, 3233, 1987.
2. Brown, M. S. and Goldstein, J. L., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed., Pergamon Press, New York, 1990, 874.
3. Goldstein, J. L. and Brown, M. S., Regulation of the mevalonate pathway, Nature, 343, 425, 1990.
4. Brown, M. S., Faust, J. R., Goldstein, J. L., Kaneko, I., and Endo, A., Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase, J. Biol. Chem., 253, 1121, 1978.
5. Nakanishi, M., Goldstein, J. L., and Brown, M.S., Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme, J. Biol. Chem., 263, 8929, 1988.
6. Gaylor, J. R., Biosynthesis of Isoprenoid Compounds, Vol. 1, John Wiley & Sons, New York, 1981, 481.
7. Frye, L. L. and Leonard, D. A., Dual-action inhibitors of cholesterol biosynthesis: Lanosterol analogs that inhibit lanosterol 14α-methyl demethylase and suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, in Regulation of Isopentenoid Metabolism, ACS Symposium Series 497, Nes, W. D., Parish, E. J., and Trzaskos, J. M. Eds., American Chemical Society, Washington, D.C. 1992, 94.
8. Fischer, R. T., Trzaskos, J. M., Magolda, R. L., Ko, S. S., Brosz, C. S., and Larsen, B., Lanosterol 14α-methyl demethylase. Isolation and characterization of the third metabolically generated oxidative demethylation intermediate, J. Biol. Chem., 266, 6124, 1991.
9. Vaz, A. D. N., Roberts, E. S., and Coon, M. J., Olefin formation in the oxidative deformylation of aldehydes by cytochrome P-450. Mechanistic implications for catalysis by oxygen-derived peroxide, J. Am. Chem. Soc., 113, 5886, 1991.
10. Cole, P. A. and Robinson, C. H., A peroxide model reaction for placental aromatase. J. Am. Chem. Soc., 110, 1284, 1988.
11. Trzaskos, J. M., Fischer, R. T., and Favata, M. F., Mechanistic studies of lanosterol C-32 demethylation. Conditions which promote oxysterol intermediate accumulation during the demethylation process, J. Biol. Chem., 261, 16937, 1986.
12. Akhtar, M., Freeman, C. W., Wilton, D. C., Boar, R. B., and Copsey, D. B., The pathway for the removal of the 15α-methyl group of lanosterol. The role of lanost-8-ene-3β,32-diol in cholesterol biosynthesis, Bioorg. Chem., 6, 473, 1977.
13. Akhtar, M., Alexander, K., Boar, R. B., McGhie, J. F., and Barton, D. H. R., Chemical and enzymatic studies on the characterization of intermediates during the removal of the 14α-methyl group in cholesterol biosynthesis, Biochem. J., 169, 449, 1978.
14. Bossard, M. J., Tomaszek, T. A., Jr., Metcalf, B. W., and Adams, J. L., A novel, convenient assay of lanosterol 14α-methyl demethylase, Bioorganic Chem., 17, 385, 1989.
15. 14DM from rat liver microsomes, Chem. Pharm. Bull., 36, 3049, 1988.
16. Gibbons, G. F., Pullinger, C. R., and Mitropoulos, K. A., Studies on the mechanism of lanosterol 14α-demethylation, Biochem. J., 183, 309, 1979.
17. Gibbons, G. E, Pullinger, C. R., Chen, H. W., Cavenee, W. K., and Kandutsch, A. A., Regulation of cholesterol biosynthesis in cultured cells by probable natural precursor sterols, J. Biol. Chem., 255, 395, 1980.
18. Kandutsch, A. A. and Taylor, F. R., Control of de novo cholesterol biosynthesis, in Lipoproteins and Cholesterol Metabolism in Steroidogenic Tissues, Straus. J. F., III, Menon, K. M. J., Eds., George F. Stickley Co., Philadelphia, PA, 1985, 1.
19. Gibbons, G. F., Molecular control of 3-hydroxy-3-methylglutaryl coenzyme A reductase: The role of oxygenated sterols, in 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase, Sabine, I. R., Ed., CRC Press, Boca Raton, FL, 1983, 153.
20. Kandutsch, A. A., Chen, H. W., and Heiniger, H.-J., Biological activity of some oxygenated sterols, Science, 201, 498, 1978.
21. Kandutsch, A. A. and Chen, H. W., Inhibition of sterol synthesis in cultured mouse cells by 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol, J. Biol. Chem., 248, 8408, 1973.
22. Ness, G. C., Eales, S., Lopez, D., and Zhao, Z., Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression by sterol and nonsterols in rat liver, Arch. Biochem. Biophys., 308, 420, 1994.
23. Kandutsch, A. A. and Chen, H. W., Inhibition of sterol synthesis in cultured mouse cells by cholesterol derivatives oxygenated in the side chain, J. Biol. Chem., 249, 6057, 1974.
24. Saucier, S. E., Kandutsch, A. A., Taylor, F. R., Spencer, T. A., Phirwa, S., and Gayen, A. K., Identification of regulatory oxysterols, 24(S),25-epoxycholesterol and 25-hydroxycholesterol in cultured fibroblasts, J. Biol. Chem., 260, 14571, 1985.
25. Osborne, T. S., Goldstein, G. L., and Brown, M. S., 5′-end of HMG-CoA reductase gene contains sequence responsible for cholesterol mediated inhibition of transcription, Cell, 42, 203, 1985.
26. Taylor, F. R., Saucier, S. E., Shown, E. P., Parish, E. J., and Kandutsch, A. A., Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase, J. Biol. Chem., 259, 12383, 1984.
27. Gibbons, G. F., Pullinger, C. R., Chen, H. W., Cavenee, W. K., and Kandutsch, A. A., Regulation of cholesterol biosynthesis in cultured cells by probable natural precursor sterols, J. Biol. Chem., 255, 395, 1980.
28. Trzaskos, J. M., Favata, M. F., Fischer, R. T., and Stam, S. H., In situ accumulation of 3β-hydroxylanost-8-en-32-al in hepatocyte cultures, J. Biol. Chem., 262, 12261, 1987.
29. Favata, M. F., Trzaskos, J. M., Chen, H. W., Fischer, R. T., and Greenberg, R. S., Modulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by azole antimycotics requires lanosterol demethylation, but not 24,25-epoxylanosterol formation, J. Biol. Chem., 262, 12254, 1987.
30. Panini, S. R., Delate, T. A., and Sinensky, M., Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 24(S),25-oxidolanosterol, J. Biol. Chem., 267, 12647, 1992.
31. Trzaskos, J. M., Magolda, R. L., Favata, M. F., Fischer, R. T., Johnson, P. R., Chen, H. W., Ko, S S., Leonard, D. A., and Gaylor, J. L., Modulation of 3-hydroxy-3-methyl-CoA reductase by 15α-fluorolanost-7-en-3β-ol. A mechanism-based inhibitor of cholesterol biosynthesis, J. Biol. Chem., 268, 22591, 1993.
32. Leonard, D. A., Kotarski, M. A., Tessiatore, J. E., Favata, M. F., and Trzaskos, J. M., Post-transcriptional regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by 3β-hydroxylanost-8-en-32-al, an intermediate in the conversion of lanosterol to cholesterol, Arch. Biochem. Biophys., 310, 152, 1994.
33. Anderson, J. A., Leonard, D. A., Cusack, K. P., and Frye, L. L., 15-Substituted lanosterols: Post-transcriptional suppressors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, Arch. Biochem. Biophys., 316, 190, 1995.
34. Liscum, L., Luskey, K. L., Chin, D. J., Ho, Y. K., Goldstein, J. L., and Brown, M. S., Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its mRNA in rat liver as studied with a monoclonal antibody and cDNA probe, J. Biol. Chem., 258, 8450, 1983.
35. Ness, G. C., Keller, R. K., and Pendleton, L. C., Feedback regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity by dietary cholesterol is not due to altered mRNA levels, J. Biol. Chem., 266, 14854, 1991.
36. Spady, D. K. and Cuthbert, J. A., Regulation of hepatic sterol metabolism in the rat, J. Biol. Chem., 267, 5584, 1992.
37. Ko, S. S., Brosz, C. S., Chen, H. W., Favata, M. F., Gaylor, J. L., Johnson, P. R., Magolda, R. L., Stam, S. H., and Trzaskos, J. M., Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase gene expression - a new approach to cholesterol biosynthesis inhibitors. Presented at the FASEB/ACS Satellite Symposium, Biosynthesis and Utilization of Isoprenoids (Reductase V), April 1991, Atlanta, GA.
38. Mayer, R. J., Adams, J. L., Bossard, M. J., and Berkhout, T. A., Effects of a novel lanosterol 14α-methyl demethylase inhibitor on the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase in HepG2 cells, J. Biol. Chem., 266, 20070, 1991.
39. Frye, L. L., Cusack, K. P., and Leonard, D. A., 32-Methyl-32-oxylanosterels: Dual-action inhibitors of cholesterol biosynthesis, J. Med. Chem., 36, 410, 1993.
40. Frye, L. L., Cusack, K. P., Leonard, D. A., and Anderson, J. A., Oxolanosterol oximes: Dual-action inhibitors of cholesterol biosynthesis, J. Lipid Res., 35, 1333, 1994.
41. Schroepfer, G. J., Jr., Parish, E. J., Tsuda, M., Raulston, D. L., and Kandutsch, A. A., Inhibition of sterol biosynthesis in animal cells by 14α-alkyl-substituted 15-oxygenated sterols, J. Lipid Res., 20, 994, 1979.
42. Pinkerton, F. D., Izumi, A., Anderson, C. M., Miller, L. E., Kisic, A., and Schroepfer, G. J., Jr., 14α-ethyl-5α-cholest-7-ene-3β,15α-diol, a potent inhibitor of sterol biosynthesis, has two sites of action in cultured mammalian cells, J. Biol. Chem., 257, 1929, 1982.
43. Raulston, D. L., Pajewski, T. N., Miller, L. R., Phillip, U. W., Shapiro, D. J., and Schroepfer, G. J., Jr., Inhibition of cholesterol biosynthesis in cell-free preparations of rat liver by 14α-ethyl-5α-cholest-7-ene-3β,15α-diol, Biochem. Int., 1, 113, 1980.
44. Schroepfer, G. J., Jr., Parish, E. J., Tsuda, M., and Kandutsch, A. A., Inhibitors of sterol synthesis. Chemical syntheses, properties and effects of 4,4-dimethyl-15-oxygenated sterols on sterol synthesis and on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells, Chem. Phys. Lipids, 47, 187, 1988.
45. Morisaki, M., Sonoda, Y., Makino, T., Ogihara, N., Ikekawa, N., and Sato, Y., Inhibitory effect of 15-oxygenated sterols on cholesterol synthesis from 24,25-dihydrolanosterol, J. Biochem., 99, 597, 1986.
46. Gaylor, J. L., Johnson, P. R., Ko, S. S., Magolda, R. L., Stam, S. H., and Trzaskos, J. M., Steroid derivatives useful as hypocholesterolemics, U.S. Patent 5 041 432, 1991.
47. Beusen, D. D., Carrell, J. L., and Covey, D. F., Metabolism of 19-methyl-substituted steroids by human placental aromatase. Biochemistry, 26, 7833, 1987.
48. Trzaskos, J. M., Bowen, W. D., Shaflee, A., Fischer, R. T., and Gaylor, J. L., Cytochrome P-450-dependent oxidation of lanosterol in cholesterol biosynthesis, J. Biol. Chem., 259, 13402, 1984.
49. Chen, H. W., Leonard, D. A., Fischer R. T., and Trzaskos, J. M., A mammalian mutant cell lacking detectable lanosterol 14α-methyl demethylase activity, J. Biol. Chem., 263, 1248, 1988.
50. Sheets, J. J. and Vickery, L. E., Active site-directed inhibitors of cytochrome P-450scc. Structural and mechanistic implications of a side chain-substituted series of amino-steroids, J. Biol. Chem., 258, 11446, 1983.
51. Wright, J. N., Calder, J. R., and Akhtar, M., Steroidal C-19 sulphur and nitrogen derivatives designed as aromatase inhibitors, J. Chem. Soc. Chem. Commun., 1733, 1985.
52. Pinkerton, F. D., Spilman, C. H., Via, D. P., and Schroepfer, G. J., Jr., Differing effects of three oxysterols on low density lipoproteins metabolism in HepG2 cells, Arch. Biochem. Biophys., 193, 1091, 1993.