Potent and selective steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone

Journal of Medicinal Chemistry

Volumn 52, Issue 23, 2009, Pages 7488-7502

  Bellavance, Edith ^a   Luu The, Van ^a   Poirier, Donald ^a  

^a LAVAL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

4 METHYL 4 AZA 5 ALPHA ANDROSTANE; ANDROSTANE DERIVATIVE; ANDROSTANOLONE; ESTRONE; OXIDOREDUCTASE INHIBITOR; STEROID 5ALPHA REDUCTASE 1; STEROID 5ALPHA REDUCTASE 2; TESTOSTERONE 17BETA DEHYDROGENASE; TESTOSTERONE 17BETA DEHYDROGENASE TYPE 7; UNCLASSIFIED DRUG;

ARTICLE; ENZYME INHIBITION; ENZYME MECHANISM; HUMAN; HUMAN CELL; IC 50; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STRUCTURE ACTIVITY RELATION;

17-HYDROXYSTEROID DEHYDROGENASES; ANDROSTANE-3,17-DIOL; ANDROSTANES; BIOCATALYSIS; CELL LINE; DIHYDROTESTOSTERONE; ENZYME INHIBITORS; ESTRADIOL; ESTRONE; HUMANS; INHIBITORY CONCENTRATION 50; OXIDATION-REDUCTION; SUBSTRATE SPECIFICITY;

EID: 72249090207     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900921c     Document Type: Article

References (50)

1. (a) Moeller, G.; Adamski, J. Integrated view on 17beta-hydroxysteroid dehydrogenases. Mol. Cell. Endocrinol. 2009, 301, 7-19.
2. (b) Luu-The, V.; Bélanger, A.; Labrie, F. Androgen biosynthetic pathways in the human prostate. Best Pract. Res., Clin. Endocrinol. Metab. 2008, 22, 207-221.
3. (c) Lukacik, P.; Kavanagh, K. L.; Oppermann, U. Structure and function of human 17β-hydroxysteroid dehydrogenases. Mol. Cell. Endocrinol. 2006, 248, 61-71.
4. (d) Vihko, P.; Herrala, A.; Harkonen, P.; Isomaa,V.; Kaija, H.; Kurkela, R.; Pulkka, A. Control of cell proliferation by steroids: the role of 17β-HSDs. Mol. Cell. Endocrinol. 2006, 248, 141-148.
5. (e) Luu-The, V. Analysis and characteristics of multiple types of human 17β-hydroxysteroid dehydrogenase. J. Steroid Biochem. Mol. Biol. 2001, 76, 143-151.
6. (a) Duan, W. R.; Linzer, D. I. H.; Gibori, G. Cloning and characterization of an ovarian-specific protein that associates with the short form of the prolactin receptor. J. Biol. Chem. 1996, 271, 15602-15607.
7. (b) Shehu, A.; Mao, J.; Gibori, G. B.; Halperin, J.; Le, J.; Sangeeta Devi, Y.; Merrill, B.; Kiyokawa, H.; Gibori, G. Hsd17b7 (PRAP/17β- hydroxysteroid dehydrogenase type 7) gene plays a crucial role in embryonic development and fetal survival. Mol. Endocrinol. 2008, 22, 2268-2277.
8. Nokelainen, P.; Peltoketo, H.; Vihko, R.; Vihko, P. Expression cloning of a novel estrogenic mouse 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase (m17β-HSD7), previously described as a prolactin receptor-associated protein (PRAP) in rat. Mol. Endocrinol. 1998, 12, 1048-1059.
9. (a) Peltoketo, H.; Nokelainen, P.; Piao, Y.; Vihko, R.; Vihko, P. Two 17β-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7. J. Steroid Biochem. Mol. Biol. 1999, 69, 431-439.
10. (b) Nokelainen, P.; Peltoketo, H.; Mustonen, M.; Vihko, P. Expression of mouse 17β-hydroxysteroid dehydrogenase type 7 in the ovary, uterus, and placenta: localisation from implantation to late pregnancy. Endocrinology 2000, 141, 772-778. (Pubitemid 32250502)
11. (c) Pelletier, G.; Luu-The, V.; Labrie, F. Localization of type 7 17β-hydroxysteroid dehydrogenase in mouse tissues. In situ hybridization studies. J. Steroid Biochem. Mol. Biol. 2005, 93, 49-57.
12. (a) Krazeisen, A.; Breitling, R.; Imai, K.; Fritz, S.; Moller, G.; Adamski, J. Determination of cDNA, gene structure and chromosomal localization of the novel human 17β-hydroxysteroid dehydrogenase type 7. FEBS Lett. 1999, 460, 373-379. (Pubitemid 29495972)
13. (b) Breitling, R.; Krazeisen, A.; Moller, G.; Adamski, J. 17β-Hydroxysteroid dehydrogenase type 7, an ancient 3-ketosteroid reductase of cholesterogenesis. Mol. Cell. Endocrinol. 2001, 171, 199-204.
14. (c) Torn, S.; Nokelainen, P.; Kurkela, R.; Pulkka, A.; Menjivar, M.; Ghosh, S.; Coca-Prados, M.; Peltoketo, H.; Isomaa, V.; Vihko, P. Production, purification, and functional analysis of recombinant human and mouse 17β-hydroxysteroid dehydrogenase type 7. Biochem. Biophys. Res. Commun. 2003, 305, 37-45.
15. (d) Robert, A. Caractérisation de la 17β-HSD de Type 7 chez l'Humain. M.Sc. Thesis, Université Laval, Quebec, Canada, 2004; 86 pp.
16. (e) Lui, H. Clonage et Caractérisation de Deux Formes de la 17β-Hydroxystéroide Déshydrogénase de Type 7 chez l'Humain. M.Sc. Thesis, Université Laval, Quebec, Canada, 2001; 85 pp.
17. (f) Song, D.; Liu, G.; Luu-The, V.; Zhao, D.; Wang, L.; Zhang, H.; Xueling, G.; Li, S.; Désy, L.; Labrie, F.; Pelletier, G. Expression of aromatase and 17β-hydroxysteroid dehydrogenase types 1, 7 and 12 in breast cancer. An immunocytochemical study. J. Steroid Biochem. Mol. Biol. 2006, 101, 136-144.
18. (a) Weihua, Z.; Lathe, R.; Warner, M.; Gustafsson, J. A. An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 13589-13594.
19. (b) Picciarelli-Lima, P.; Oliveira, A. G.; Reis, A. M.; Kalapothakis, E.; Mahecha, G. A. B.; Hess, R. A.; Oliveira, C. A. Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects, in modulating the aquaporin-9 expression in the rat efferent ductules. Reprod. Biol. Endocrinol. 2006, 4, 51.
20. (a) Marijanovic, Z.; Laubner, D.; Moller, G.; Gege, C.; Husen, B.; Adamski, J.; Breitling, R. Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis. Mol. Endocrinol. 2003, 17, 1715-1725.
21. (b) Ohnesorg, T.; Adamski, J. Promoter analyses of human and mouse 17beta-hydroxysteroid dehydrogenase type 7. J. Steroid Biochem. Mol. Biol. 2005, 94, 259-261.
22. (c) Ohnesorg, T.; Keller, B.; Hrabé de Angelis, M.; Adamski, J. Transcriptional regulation of human and murine 17β-hydroxysteroid dehydrogenase type-7 confers its participation in cholesterol biosynthesis. J. Mol. Endocrinol. 2006, 37, 185-197.
23. Krusche, C. A.; Moller, G.; Beier, H.; Adamski, J. Expression and regulation of 17β-hydroxysteroid dehydrogenase 7 in the rabbit. Mol. Cell. Endocrinol. 2001, 171, 169-177.
24. (a) Schwabe, I.; Husen, B.; Einspanier, A. Expression of the estradiol-synthesizing 17beta-hydroxysteroid dehydrogenases type 1 and type 7 in the nonhuman primate Callithrix jacchus. Mol. Cell. Endocrinol. 2001, 171, 187-192.
25. (b) Husen, B.; Adamski, J.; Bruns, A.; Deluca, D.; Fuhrmann, K.; Moller, G.; Schwabe, I.; Einspanier, A. Characterization of 17β-hydroxysteroid dehydrogenase type 7 in reproductive tissues of the Marmoset monkey. Biol. Reprod. 2003, 68, 2092-2099.
26. (a) Poirier, D. New cancer drugs targeting the biosynthesis of estrogens and androgens. Drug Dev. Res. 2008, 69, 304-318.
27. (b) Poirier, D. Recent advances in development of inhibitors of 17β-hydroxysteroid dehydrogenases. Anti-Cancer Agents Med. Chem. 2009, 9, 642-660.
28. (c) Day, J.; Tutill, H.; Purohit, A.; Reed, M. Design and validation of specific inhibitors of 17{β}-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis. Endocr.-Relat. Cancer 2008, 15, 665-692.
29. (d) Brozic, P.; Lanisnik Risner, T; Gobec, S. Inhibitors of 17β-hydroxysteroid dehydrogenase type 1. Curr. Med. Chem. 2008, 15, 137-150.
30. (e) Poirier, D. Inhibitors of 17β-hydroxysteroid dehydrogenases. Curr. Med. Chem. 2003, 10, 453-477.
31. (f) Smith, J. H.; Nicholls, J. P.; Simons, C.; Le Lain, R. Inhibitors of steroidogenesis as agents for the treatment of hormone-dependant cancers. Expert Opin. Ther. Pat. 2001, 11, 789-824.
32. (g) Penning, T. M. 17β-hydroxysteroid dehydrogenase: inhibitors and inhibitor design. Endocr.-Relat. Cancer 1996, 3, 41-56.
33. Labrie, F.; Poulin, R.; Simard, J.; Zhao, H. F.; Labrie, C.; Dauvois, S.; Dumont, M.; Hatton, A. C.; Poirier, D.; Mérand, Y. Interactions between estrogens, androgens, progestins, and glucocorticoids in ZR-75-1 human breast cancer cells. Ann. N.Y. Acad. Sci. 1990, 595, 130-148.
34. Bellavance, E.; Luu-The, V.; Poirier, D. First inhibitors of the steroidogenic enzyme type 7 17β-hydrosteroid dehydrogenase. Lett. Drug Des. Discovery 2004, 1, 194-197.
35. Bydal, P.; Luu-The, V.; Labrie, F.; Poirier, D. Steroidal lactones as inhibitors of 17β-hydroxysteroid dehydrogenase type 5: chemical synthesis, enzyme inhibitory activity, and assessment of estrogenic and androgenic activities. Eur. J. Med. Chem. 2009, 44, 632-644.
36. (a) Dufort, I.; Rheault, P.; Huang, X.-F.; Soucy, P.; Luu-The, V. Characteristics of a highly labile human type 5 17β-hydroxysteroid dehydrogenase. Endocrinology 1999, 140, 568-574. (Pubitemid 29058186)
37. (b) Lin, H. K.; Jez, J. M.; Schlegel, B. P.; Peehl, D. M.; Pachter, J. A.; Penning, T. M. Expression and characterization of recombinant type 2 3α-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3α/17β-HSD activity and cellular distribution. Mol. Endocrinol. 1997, 11, 1971-1984.
38. (c) Penning, T. M.; Burczynski, M. E.; Jez, J. M.; Lin, H. K.; Ma, H.; Moore, M.; Ratnam, K.; Palackal, N. Structure-function aspects and inhibitor design of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3). Mol. Cell. Endocrinol. 2001, 171, 137-149.
39. Li, X.; Singh, M. S.; Labrie, F. Synthesis and in vitro activity of 17β-(N-alkyl/arylformamido)- and 17β-[(N-alkyl/aryl)alkyl/ arylamido]-4-methyl-4-aza-3-oxo-5α-androstan-3-ones as inhibitors of human 5α-reductases and antagonists of the androgen receptor. J. Med. Chem. 1995, 38, 1158-1173.
40. Rasmusson, G.; Reynolds, G.; Steinberg, N.; Walton, E.; Patel, G.; Liang, T.; Cascieri, M.; Cheung, A.; Brooks, J.; Berman, C. Azasteroids: structure - activity relationships for inhibition of 5α-reductase and of androgen receptor binding. J. Med. Chem. 1986, 29, 2298-2305.
41. 3 receptors. Bioorg. Med. Chem. Lett. 2002, 12, 619-622.
42. (a) Bogeso, K.; Christensen, A. V.; Hyttel, J.; Liljefors, T. 3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine and serotonin uptake. J. Med. Chem. 1985, 28, 1817-1828.
43. (b) Sterling, J.; Herzig, Y.; Goren, T.; Finkelstein, N.; Lerner, D.; Goldenberg, W.; Miskolczi, I.; Molnar, S.; Rantal, F.; Tamas, T.; Toth, G.; Zagyva, A.; Zekany, A.; Finberg, J.; Lavian, G.; Gross, A.; Friedman, R.; Razin, M.; Huang, W.; Krais, B.; Chorev, M.; Youdim, M. B.; Weinstock, M. Novel dual inhibitors of AchE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease. J. Med. Chem. 2002, 45, 5260-5279.
44. Pine, S. H. Organic Chemistry, 5th ed.; McGraw-Hill, Inc.: New York, 1987; 1057 pp.
45. Puranen, T.; Poutanen, M.; Ghosh, D.; Vihko, P.; Vihko, R. Characterization of structural and functional properties of humain 17β-hydroxysteroid dehydrogenase type 1 using recombinant enzymes and site-directed mutagenesis. Mol. Endocrinol. 1997, 11, 77-86.
46. (a) Flores, E; Bratoeff, E.; Cabeza, M.; Ramirez, E.; Quiroz, A.; Heuze, I. Steroid 5α-reductase inhibitors. Mini-Rev. Med. Chem. 2003, 3, 225-237.
47. 17α and 5α-steroid reductase. Nat. Prod. Rep. 1998, 15, 495-512.
48. Kenemans, P.; Bosman, A. Breast cancer and post-menopausal hormone therapy. Best Pract. Res., Clin. Endocrinol. Metab 2003, 17, 123-137.
49. Harkonen, P.; Torn, S.; Kurkela, R.; Porvari, K.; Pulka, A.; Lindfors, A.; Isamaa, V.; Vihko, P. Sex hormone metabolism in prostate cancer cells during transition to an androgen-independent state. J. Clin. Endocrinol. Metab. 2003, 88, 705-712.
50. Tremblay, M. R; Lin, S. X.; Poirier, D. Chemical synthesis of 16β-propylaminoacyl derivatives of estradiol and their inhibitory potency on type 1 17β-hydroxysteroid dehydrogenase and binding affinity on steroid receptors. Steroids 2001, 66, 821-831. (Pubitemid 32884309)