Effects of Inhibitors on the P450-Dependent Metabolism of Endogenous Compounds in Fungi, Protozoa, Plants and Vertebrates

  • Hugo Vanden Bossche
  • Patrick Marichal
  • Gustaaf Willensens
  • Paul A. J. Janssen
Part of the NATO ASI Series Advanced Science Institutes Series book series (NSSA, volume 202)


A great number of the present antifungal agents belong to the class of nitrogen heterocycle derivatives. Examples are the pyrimidine antifungals, triarimol, fenarimol and nuarimol, the Pyridine derivative, buthiobate, the imidazoles, miconazole, clotrimazole, econazole, imazalil, tioconazole, bifonazole, sulconazole and ketoconazole and finally the triazole antifungals, azaconazole, propiconazole, terconazole, fluconazole, itraconazole and saperconazole. All these antifungal agents have been shown to inhibit ergosterol synthesis (the main sterol in most yeasts and fungi) by interacting with the cytochrome P450-dependent 14ß-demethylation (P45014DM) of lanosterol in e.g. Saccharomyces cerevisiae or of 24-methylenedihydrolanosterol in most fungal cells (for reviews see refs. 1–4).


Heme Iron Imidazole Derivative Sterol Biosynthesis Sterol Synthesis Azole Antifungal 
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  1. 1.
    H. Vanden Bossche, Mode of action of Pyridine, pyrimidine and azole antifungals, in: “Sterol biosynthesis inhibitors. Pharmaceutical and agrochemical aspects”, D. Berg and M. Plempel, eds., Ellis Horwood, Chichester, England (1988)Google Scholar
  2. 2.
    Y. Yoshida, Cytochrome P450 of fungi: primary target for azole antifungal agents, in: “Current topics in medical mycology”, Vol.2, M.R. McGinnis, ed., Springer Verlag, New York (1988)Google Scholar
  3. 3.
    P.A.J. Janssen and H. Vanden Bossche, Mode of action of cytochrome P-450 monooxygenase inhibitors. Focus on azole derivatives, Arch. Pharm. Chem. 15: 23–40 (1987)Google Scholar
  4. 4.
    H. Vanden Bossche, P. Marichal, J. Gorrens, D. Bellens, H. Verhoeven, M.-C. Coene, W. Lauwers and P.A.J. Janssen, Interaction of azole derivatives with cytochrome P-450 isozymes in yeast, fungi, plants and mammalian cells, Pestic. Sci. 21: 289–306 (1987)CrossRefGoogle Scholar
  5. 5.
    C. F. Wilkinson, K. Hetnarski and T.O. Yellin, Imidazole derivatives-A new class of microsomal enzyme inhibitors, Biochem. Pharmacol. 21: 3187–3192 (1972)PubMedCrossRefGoogle Scholar
  6. 6.
    P.R. Ortiz de Montellano and N.O. Reich, Inhibition of cytochrome P-450 enzymes, in: “Cytochrome P-450 structure, mechanism and biochemistry”, P.O. Ortiz de Montellano, ed., Plenum Press, New York (1986)Google Scholar
  7. 7.
    N.N. Ragsdale and H.D. Sisler, Inhibition of ergosterol synthesis in Ustilago maydis by the fungicide triarimol, Biochem. Biophys. Res. Commua. 46: 2048–2053 (1972)CrossRefGoogle Scholar
  8. 8.
    N.N. Ragsdale and H.D. Sisler, Mode of action of triarimol in Ustilago maydis, Pesticide Biochem. 3: 20–29 (1973)CrossRefGoogle Scholar
  9. 9.
    N.N. Ragsdale, Specific effects of triarimol on sterol synthesis in Ustilago maydis, Biochim. Biophys. Acta 380: 81–96 (1975)PubMedGoogle Scholar
  10. 10.
    H.D. Sisler and N.N. Ragsdale, Fungotoxicity and growth regulation involving aspects of lipid biosynthesis, Neth. J. Plant Path. 83 (suppl.l): 81–91(1977)CrossRefGoogle Scholar
  11. 11.
    T. Kato. Sterol biosynthesis in fungi, a target for broad spectrum fungicides, in: “Chemistry of plant protection. 1. Sterol biosynthesis, inhibitors and anti-feeding compounds”, G. Haug and H. Hoffmann, eds., Springer Verlag, Berlin (1986)CrossRefGoogle Scholar
  12. 12.
    Y. Aoyama, Y. Yoshida, S. Hata, T. Nishino and H. Katsuki, Buthiobate: a potent inhibitor for yeast cytochrome P-450 catalyzing 14α-demethylation of lanosterol, Biochem. Biophys. Res. Commun. 115: 642–647 (1983)PubMedCrossRefGoogle Scholar
  13. 13.
    C.F. Wilkinson, K. Hetnarski and L.J. Hicks, Substituted imidazoles as inhibitors of microsomal oxidation and insecticide synergists, Pest. Biochem. Physiol. 4: 299–312 (1974)CrossRefGoogle Scholar
  14. 14.
    S. Hata, T. Nishino, H. Katsuki, Y. Aoyama and Yoshida, Y., Two species of cytochrome P-450 in ergosterol biosynthesis of yeast, Biochem. Biophys. Res. Commun., 116: 162–166 (1983)PubMedCrossRefGoogle Scholar
  15. 15.
    S. Hata, T. Nishino, M. Komori and H. Katsuki, Involvement of cytochrome P-450 in Δ22-desaturation in ergosterol biosynthesis in yeast, Biochem. Biophys. Res. Commun., 103: 272–277 (1981)PubMedCrossRefGoogle Scholar
  16. 16.
    Y. Yoshida, Y. and Y Aoyama, Y., Effects of buthiobate, a fungicide, on cytochrome P-450 of rat liver microsomes, J. Pharmacobiol. Dyn. 8: 432–439 (1985)CrossRefGoogle Scholar
  17. 17.
    J. L. Sherald, N. N. Ragsdale and H. D. Sisler, Similarities between the systemic fungicides triforine and triarimol, Pestic. Sci. 4: 719–727 (1973)CrossRefGoogle Scholar
  18. 18.
    T. Kato, Biosynthetic processes of ergosterol as the target of fungicides, in: “Pesticide chemistry, human welfare and the environment: mode of action and toxicology”, S. Matsunaka, D.H. Hutson and S.D. Murphy, eds., Pergamon Press, Oxford (1982)Google Scholar
  19. 19.
    H. Buchenauer, Hemmung der Ergosterinbiosynthese in Ustilago avenae durch Triadimefon und Fluorotrimazol, Z. Pflanzenkr. Pflanzenschutz, 83: 363–367 (1976)Google Scholar
  20. 20.
    K.A. Mitropoulos, G.F. Gibbons, C.M. Connell and R.A. Woods, Effect of triarimol on cholesterol biosynthesis in rat liver subcellular fractions, Biochem. Biophys. Res. Commun. 71: 892–900 (1976)PubMedCrossRefGoogle Scholar
  21. 21.
    S.D. Atkins, B. Morgan, K.H. Baggaley and J. Green, Isolation of 2, 3-oxidosqualene from the liver of rats treated with 1-dodecylimidazole, a novel hypocholesteremic agent, Biochem. J. 130: 153–157 (1972)Google Scholar
  22. 22.
    G. Matolsky, M. Kovács, M. Tüske and B. Toth, Studies on the antifungal action of potential steroid inhibitors, Neth. J. Plant Pathol. 83 (Suppl. 1): 39–47 (1977)CrossRefGoogle Scholar
  23. 23.
    M.S. Marriott, Inhibition of sterol biosynthesis in Candida albicans by imidazole-containing antifungals, J. Gen. Microbiol. 117: 253–255 (1980)PubMedGoogle Scholar
  24. 24.
    M.J. Henry and H.D. Sisler, Effects of miconazole and dodecylimidazole on sterol biosynthesis in Ustilago maydis, Antimicrob. Ag. Chemother. 15: 603–607 (1979)Google Scholar
  25. 25.
    H. Vanden Bossche, W. Lauwers, G. Willemsens, P. Marichal, F. Cornelissen and W. Cools, Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles. Inhibition of isoprenoid biosynthesis, Pestic. Sci. 15: 188–198 (1984)CrossRefGoogle Scholar
  26. 26.
    H. Vanden Bossche, G. Willemsens, W. Cools, F. Cornelissen, W.F. Lauwers and J.M. Van Cutsem, In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis, Antimicrob. Ag. Chemother. 17: 922–928 (1980)Google Scholar
  27. 27.
    H. Vanden Bossche, G. Willemsens, W. Cools, W.F. Lauwers and L. Le Jeune, Biochemical effects of miconazole on fungi. II. Inhibition of ergosterol biosynthesis in Candida albicans, Chem. Biol. Interact. 21: 59–78 (1978)PubMedCrossRefGoogle Scholar
  28. 28.
    G.W. Pye and M.S. Marriott, Inhibition of sterol C14-demethylation by imidazole containing antifungals, Sabouraudia 20: 325–329(1982)PubMedCrossRefGoogle Scholar
  29. 29.
    J.D. Weete, M.S. Sancholle and C. Montant, Effects of triazoles on fungi: II. lipid composition of Taphrina deformans, Biochim. Biophys, Acta 753: 19–29(1983)Google Scholar
  30. 30.
    E. Ebert, J. Gaudin, W. Muecke, K. Ramsteiner, C. Vogel and H. Fuhrer, Inhibition of ergosterol biosynthesis by etaconazole in Ustilago maydis, Z. Naturforsch. 38c: 28–34 (1983)Google Scholar
  31. 31.
    G. Cauwenbergh and H. Vanden Bossche, Terconazole pharmacology of a new antimycotic agent, J.Reprod. Med. 34: 588–592(1989)PubMedGoogle Scholar
  32. 32.
    M.S. Marriott and K. Richardson, The discovery and mode of action of fluconazole, in: “Recent trends in the discovery and development and evaluation of antifungal agents”, R.A. Fromtling, ed., J.R. Prous Science Publishers, Barcelona (1987)Google Scholar
  33. 33.
    Y. Yoshida and Y. Aoyama, Interaction of azole fungicides with yeast cytochrome P-450 which catalyzes lanosterol 14α-demethylation, in: “In vitro and in vivo evaluation of antifungal agents”, K. Iwata and H. Vanden Bossche, eds., Elsevier Science Publishers, Amsterdam (1986)Google Scholar
  34. 34.
    H. Vanden Bossche, P. Marichal, J. Gorrrens, H. Geerts and P.A.J. Janssen, Mode of action studies. Basis for the search of new antifungal agents, Ann. N.Y. Acad. Sci. 544: 191–207(1988)CrossRefGoogle Scholar
  35. 35.
    T.D. Rogerson, C.F. Wilkinson and K. Hetarski, Steric factors in the inhibitory interaction of imidazoles with microsomal enzymes, Biochem. Pharmacol. 26: 1039–1042(1977)PubMedCrossRefGoogle Scholar
  36. 36.
    H. Vanden Bossche, P. Marichal, H. Geerts and P.A.J. Janssen, The molecular basis for itraconazole’s activity against Aspegillus fumigatus, in: “Aspergillus and aspergillosis”, H. Vanden Bossche, D.W.R. Mackenzie and G. Cauwenbergh, eds., Plenum Press, New York (1988)Google Scholar
  37. 37.
    H. F. Merk, H. Mukhtar, I. Kaufmann, M. Das and D.R. Bickers, Human hair follicle benzo[a]pyrene and benzo[a]pyrene-7, 8-diol metabolism: effect of exposure to a coal tar-containing shampoo, J. Invest. Dermatol., 88: 71–76(1987)PubMedCrossRefGoogle Scholar
  38. 38.
    H. Mukhtar, B.J. Del Tito, M. Das, E. P. Cherniack, A.D. Cherniack and D.R. Bickers, Clotrimazole, an inhibitor of epidermal benzo(a)pyrene metabolism and DNA binding and carcinogenicity of the hydocarbon, Canc. Res. 44: 4233–4240(1984)Google Scholar
  39. 39.
    H. Vanden Bossche, G. Willemsens, P.A.J. Janssen, (1988) Cytochrome P-450-dependent metabolism of retinoic acid in rat skin microso-mes: inhibition by ketoconazole, Skin Pharmacol 1: 176–185 (1988)CrossRefGoogle Scholar
  40. 40.
    H.F. Merk, H. Mukhtar, B. Schutte, I. Kaufmann, M. Das and D. R. Bickers, 7-Ethoxyresoruf in-O-deethylase activity in human hair roots: a potential marker for toxifying species of cytochrome P-450 isozymes, Biochem. Biophys. Res. Commun. 148: 755–761(1987)PubMedCrossRefGoogle Scholar
  41. 41.
    D.T. Hart, W.J. Lauwers, G. Willemsens, H. Vanden Bossche and F.R. Opperdoes, Perturbation of sterol biosynthesis by itraconazole and ketoconazole in Leishmania mexicana mexicana infected macrophages, Mol. Biochem. Parasitol. 33: 123–134(1989)PubMedCrossRefGoogle Scholar
  42. 42.
    G. Willemsens, W Cools and H. Vanden Bossche, Effects of miconazole and ketoconazole on sterol synthesis in a subcellular fraction of yeast and mammalian cells,. in “The Host Invader Interplay”, H. Vanden Bossche, ed., Elsevier/ North Holland Biomedical Press, Amsterdam (1980)Google Scholar
  43. 43.
    J.D. Berman, L.J. Goad, D.H. Black and G.G. Holz Jr., Effects of ketoconazole on sterol synthesis by Leishmania mexicana mexicana amastigotes in murine macrophage tumor cells, Mol. Biochem. Parasitol. 20: 85–92(1986)PubMedCrossRefGoogle Scholar
  44. 44.
    H. Vanden Bossche, G. Willemsens, P. Marichal, W. Cools and W. Lauwers, The molecular basis for the antifungal activity of N-substituted azole derivatives. Focus on R 51211, in: “Mode of action of antifungal agents”, Cambridge University Press, Cambridge (1984)Google Scholar
  45. 45.
    Y. Aoyama, Y. Yoshida, Y. Sonoda and Y. Sato, Metabolism of 32-hydroxy-24, 25-dihydrolanosterol by purified cytochrome P-45014DM from yeast. Evidence for contribution of the cytochrome to whole process of lanosterol 14α-demethylation, J. Biol. Chem. 262: 1239–1243(1987)PubMedGoogle Scholar
  46. 46.
    J.M. Trzaskos, R.T. Fisher and M.F. Favata, Mechanistic studies of lanosterol C-32 demethylation. Conditions which promote oxysterol intermediate accumulation during the demethylation process, J. Biol. Chem. 261: 16937–16942(1986)PubMedGoogle Scholar
  47. 47.
    J.M. Trzaskos and M.J. Henry, Comparative effects of the azole-based fungicide flusilazole on yeast and mammalian lanosterol 14ß-methyl demethylase, Antimicrob. Ag. Chem.: 33, 1228–1231 (1989).Google Scholar
  48. 48.
    R. De Felice, D.G. Johnson and J.N. Galgiani, Gynecomastia with ketoconazole, Antimicrob. Ag. Chemother. 19: 1073–1074(1981)Google Scholar
  49. 49.
    A. Pont, P.L. Williams, S. Azhar, R.E. Reirz, Ketoconazole blocks testosterone synthesis, Arch. Intern. Med. 142: 2137–2140(1982)PubMedCrossRefGoogle Scholar
  50. 50.
    Th. Schürmeyer and E. Nieschlag, Ketoconazole-induced drop in serum and saliva testosterone, Lancet, Nov. 13, 1098–1099, 1982.CrossRefGoogle Scholar
  51. 51.
    R.J. Santen, H. Vanden Bossche, J. Symoens, J. Brugmans and R. De Coster, Site of action of low dose ketoconazole on androgen biosynthesis in men, J. Clin. Endocrinol. Metab. 57: 732–736 (1983)PubMedCrossRefGoogle Scholar
  52. 52.
    R. De Coster, I. Caers, M.-C. Coene, W. Amery, D. Beerens and C. Haelterman, Effects of high dose ketoconazole therapy on the main plasma testicular and adrenal steroids in previously untreated prostatic cancer patients, Clin. Endocrinol. 24: 657–664(1986)CrossRefGoogle Scholar
  53. 53.
    D. Feldman, Ketoconazole and other imidazole derivatives as inhibitors of steroidogenesis, Endocrine Rev. 7: 409–420(1986)CrossRefGoogle Scholar
  54. 54.
    H. Vanden Bossche, R. De Coster and W. Amery, Pharmacological and clinical uses of ketoconazole, in: “Pharmacology and clinical uses of inhibitors of hormone secretion and action,” B.J.A. Furr and A.E. Wakeling, eds., Baillière Tindall, London (1987)Google Scholar
  55. 55.
    W.K. Amery, R. De Coster and I. Caers, Ketoconazole: from an antimycotic to a drug for prostate cancer, Dxua Develop. Res. 8: 299–307(1986)Google Scholar
  56. 56.
    J. Trachtenberg and J. Zadra, Steroid synthesis inhibition by ketoconazole: sites of action, Clin. Invest. Med. 11: 1–5(1988)PubMedGoogle Scholar
  57. 57.
    H. Vanden Bossche, W. Lauwers, G. Willemsens and W. Cools, The cytochrome P-450 dependent C17,20-lyase in subcellular fractions of the rat testis: differences in sensitivity to ketoconazole and itraconazole, in: “Microsomes and Drug Oxidations”, A.R. Boobis, J. Caldwell, F. de Matteis and C.R. Elcombe, eds., Taylor and Francis, London (1985)Google Scholar
  58. 58.
    H. Vanden Bossche, W. Lauwers, G. Willemsens and W. Cools, Ketoconazole an inhibitor of the cytochrome P-450 dependent testosterone biosynthesis, in “Therapeutic Principles in Metastatic Prostatic Cancer. Progress in Clinical and Biological Research”, Vol. 185A, F.H. Schroeder and B. Richards, eds., Alan R. Liss, New York (1985)Google Scholar
  59. 59.
    W. Lauwers, L. Le Jeune, H. Vanden Bossche and G. Willemsens, Identification of 17α, 20α-dihydroxyprogesterone in testicular extracts after incubation with ketoconazole, Biomed. Mass. Spentro. 12: 296–301(1985)CrossRefGoogle Scholar
  60. 60.
    J. Rajfer, S. Sikka, H.W. Xie and R.S. Swerdloff, Effect of ketoconazole on steroid production in rat testis, Steroids 46: 867–881(1985)PubMedCrossRefGoogle Scholar
  61. 61.
    P. Kan, M.A. Hirst and D. Feldman, Inhibition of steroidogenic cytochrome P-450 enzymes in rat testis by ketoconazole and related imidazole anti-fungal drugs, J. Steroid. Biochem. 23: 1023–1029(1985)PubMedCrossRefGoogle Scholar
  62. 62.
    Y. Higashi, M. Omura, K. Suzuki, H. Inano and H. Oshima, Ketoconazole as a possible universal inhibitor of cytochrome P-450 dependent enzymes: its mode of inhibition, Endocrinol. Japan 34: 105–115(1987)CrossRefGoogle Scholar
  63. 63.
    M. Namiki, M. Kitamura, E. Buczko and M.L. Dufau, Rat testis P-450l7α cDNA: the deduced amino acid sequence, expression and secondary structural configuration, Biochem. Biophys. Res. Commun. 157: 705–712 (1988)PubMedCrossRefGoogle Scholar
  64. 64.
    H.R. Fevold, M.C. Lorence, J.L. McCarthy, J.M. Trant, M. Kagimoto, M.R. Waterman and J.I. Mason, Rat P45017α from testis: characterization of a full-lenght cDNA encoding a unique steroid hydroxylase capable of catalyzing both Δ4-and Δ5-steroid-17, 20-lyase reactions, Mol. Endocrinol. 3: 968–975 (1989)PubMedCrossRefGoogle Scholar
  65. 65.
    T. Yanase, M. Kagimoto, S. Suzuki, K. Hashiba, E.R. Simpson and M.R. Waterman, Deletion of a phenylalanine in the N-terminal region of human cytochrome P-45017α results in partial combined 17α-hydroxylase/17, 20-lyase deficiency, J. Biol. Chem. 264: 18076–18082 (1989)PubMedGoogle Scholar
  66. 66.
    R.M. Couch, J. Muller, Y. S. Perry and J.S.D. Winter, Kinetic analysis of inhibition of human adrenal steroidogenesis by ketoconazole, J. Clin. Endocrinol. Met. 65: 551–554 (1987)CrossRefGoogle Scholar
  67. 67.
    M. Ayub and M.J. Levell, Inhibition of human adrenal steroidogenic enzymes in vitro by imidazole drugs including ketoconazole, J. steroid. Biochem. 32: 515–524(1989)PubMedCrossRefGoogle Scholar
  68. 68.
    J. Trachtenberg, N. Halpern and A. Pont, Ketoconazole a novel and rapid treatment for advanced prostatic cancer, J. Urol. 130: 152–153(1983)PubMedGoogle Scholar
  69. 69.
    J. Trachtenberg, Ketoconazole therapy in advanced prostatic cancer, J. Urol. 132: 61–63(1984)PubMedGoogle Scholar
  70. 70.
    J. Trachtenberg, Ketoconazole therapy in advanced prostatic cancer, J. Urol.. 137: 959 (1987)PubMedGoogle Scholar
  71. 71.
    W. Heyns, A. Drochmans, E. vander Schueren and F. Verhoeven, Endocrine effects of high dose ketoconazole therapy in advanced prostatic cancer, Acta Endocrinol. 110: 276–283(1985)PubMedGoogle Scholar
  72. 72.
    J.A. Witjes, P.F. del Moral, A.D.H. Geboers, L. Baert, J. Casselman, M. Stragier and F.M.J. Debruyne, Ketoconazole high dose in the treatment of metastatic prostate carcinoma, Akt. Urol. 20: 29–32(1989)CrossRefGoogle Scholar
  73. 73.
    T. Eichenberger, J. Trachtenberg, P. Toor and A. Keating, Ketoconazole: a possible direct cytotoxic effect on prostate carcinoma cells, J. Urol. 141: 190–191(1989)PubMedGoogle Scholar
  74. 74.
    H. Vanden Bossche, G. Willemsens, D. Bellens, I. Roels and P.A.J. Janssen. From 14α-demethylase inhibitors in fungal cells to androgen and oestrogen biosynthesis inhibitors in mammalian cells, Biochem. Soc. Trans. 18: 10–13(1990)Google Scholar
  75. 75.
    J.I. Mason, B.R. Carr and B.A. Murry, Imidazole antimycotics: selective inhibitors of steroid aromatization and progesterone hydroxylation, Steroids 50: 179–189(1987)PubMedCrossRefGoogle Scholar
  76. 76.
    C.J. Corbin, S. Graham-Lorence, M. McPhaul, J.I. Mason, C.R. Mendelson and E.R. Simpson, Isolation of a full-lenght cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells, Proc. Natl. Acad. Sci. 85: 8948–8952(1988)PubMedCrossRefGoogle Scholar
  77. 77.
    W. Wouters, R. De Coster, M. Krekels, J. van Dun, D. Beerens, C. Haelterman, A. Raeymaekers, E. Freyne, J. Van Gelder, M. Venet and P.A.J. Janssen, R 76713, A new specific non-steroidal aromatase inhibitor, J. steroid Biochem. 32: 781–788(1989)PubMedCrossRefGoogle Scholar
  78. 78.
    G. Cauwenbergh and J. Van Cutsem, Role of animal and human pharmacology in antifungal drug design, Ann. N.Y. Acad. Sci. 544: 264–269(1988)PubMedCrossRefGoogle Scholar
  79. 79.
    J. Van Cutsem, F. Van Gerven and P.A.J. Janssen, The in vitro and in vivo antifungal activity of itraconazole, in: “Recent trends in the discovery, development and evaluation of antifungal agents”, R.A. Fromtling, R.A., ed., J.R. Prous publishers, S.A., Barcelona (1987)Google Scholar
  80. 80.
    H. Vanden Bossche, D. Bellens, W. Cools, J. Gorrens, P. Marichal, H. Verhoeven, G. Willemsens, R De Coster, D. Beerens, C. Haelterman, M.-C. Coene, W. Lauwers and L. Le Jeune, Cytochrome P-450: target for itraconazole, Drug Develop. Res. 8: 287–298(1986)CrossRefGoogle Scholar
  81. 81.
    H. Vanden Bossche, Itraconazole: a selective inhibitor of the cytochrome P-450 dependent ergosterol biosynthesis, in: “Recent trends in the discovery and development and evaluation of antifungal agents”, R.A. Fromtling, ed., J.R. Prous Science Publishers, Barcelona (1987)Google Scholar
  82. 82.
    K. Lavrijsen, J. Van Houdt and D. Thijs, Interaction of miconazole, ketoconazole and itraconazole with rat liver microsomes, Xenobiotica 17: 45–47(1987)PubMedCrossRefGoogle Scholar
  83. 83.
    H. Vanden Bossche, G. Willemsens, P. Marichal, W. Cools and W. Lauwers, The molecular basis for the antifungal activities of N-substituted azole derivatives. Focus on R 51 211, in: “Mode of Action of Antifungal Agents”, A. P. J. Trinci and J.F. Ryley, eds., Cambridge University Press, Cambridge (1984)Google Scholar
  84. 84.
    K. Lürssen, (1988) Triazole plant growth regulators: effects and mode of action, in: “Sterol biosynthesis inhibitors. Pharmaceutical and agrochemical aspects”, D. Berg and M. Plempel, eds., Ellis Horwood Ltd, Chichester, England (1988)Google Scholar
  85. 85.
    W. Köller, Isomers of sterol synthesis inhibitors: fungicidal effects and plant growth regulator activities, Pestic. Sci. 18: 129–147 (1987)CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Hugo Vanden Bossche
    • 1
  • Patrick Marichal
    • 1
  • Gustaaf Willensens
    • 1
  • Paul A. J. Janssen
    • 1
  1. 1.Janssen Research FoundationBeerseBelgium

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