Synthesis and biological evaluation of (6- and 7-Phenyl) coumarin derivatives as selective nonsteroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1

Journal of Medicinal Chemistry

Volumn 54, Issue 1, 2011, Pages 248-261

  Starčević, Štefan ^a   Brožič, Petra ^a   Turk, Samo ^a   Cesar, Jožko ^a   Lanišnik Rižner, Tea ^a   Gobec, Stanislav ^a  

^a UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

[No Author keywords available]

Indexed keywords

3 ACETYL 7 (4 HYDROXYPHENYL) 2H CHROMEN 2 ONE; COUMARIN DERIVATIVE; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; TESTOSTERONE 17BETA DEHYDROGENASE; TESTOSTERONE 17BETA DEHYDROGENASE TYPE 1; TESTOSTERONE 17BETA DEHYDROGENASE TYPE 2; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; ENZYME ASSAY; ENZYME INHIBITION; IC 50; SUZUKI REACTION;

BINDING, COMPETITIVE; CATALYTIC DOMAIN; COUMARINS; ESTRADIOL DEHYDROGENASES; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; HUMANS; MODELS, MOLECULAR; RADIOLIGAND ASSAY; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78651083688     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm101104z     Document Type: Article

References (70)

1. Greenlee, R. T.; Hill-Harmon, M. B.; Murray, T.; Thun, M. Cancer Statistics, 2001. CA Cancer J. Clin. 2001, 51, 15 - 36.
2. Abdel-Rahman, M.; Stockton, D.; Rachet, B.; Hakulinen, T.; Coleman, M. P. What if Cancer Survival in Britain Were the Same as in Europe: How Many Deaths Are Avoidable? Br. J. Cancer 2009, 101, 5115-5124
3. Laplante, Y.; Rancourt, C.; Poirier, D. Relative Involvement of Three 17β-Hydroxysteroid Dehydrogenases (Types 1, 7 and 12) in the Formation of Estradiol in Various Breast Cancer Cell Lines Using Selective Inhibitors Mol. Cell. Endocrinol. 2009, 301, 146-153
4. Meier, M.; Möller, G.; Adamski, J. Perspectives in Understanding the Role of Human 17 β-Hydroxysteroid Dehydrogenases in Health and Disease Ann. N.Y. Acad. Sci. 2009, 1155, 15-24
5. Day, J. M.; Tutill, H. J.; Purohit, A.; Reed, M. J. Design and Validation of Specific Inhibitors of 17β-Hydroxysteroid Dehydrogenases for Therapeutic Application in Breast and Prostate Cancer, and in Endometriosis Endocr. Relat. Cancer 2008, 15, 665-692
6. Vihko, P.; Härkönen, P.; Oduwole, O.; Törn, S.; Kurkela, R.; Porvari, K.; Pulkka, A.; Isomaa, V. 17β-Hydroxysteroid Dehydrogenases and Cancers J. Steroid Biochem. Mol. Biol. 2003, 83, 119-122
7. Vihko, P.; Herrala, A.; Härkönen, P.; Isomaa, V.; Kaija, H.; Kurkela, R.; Li., Y.; Patrikainen, L.; Pulkka, A.; Soronen, P.; Törn, S. Enzymes as Modulators in Malignant Transformation J. Steroid Biochem. Mol. Biol. 2005, 93, 277-283
8. Vihko, P.; Herrala, A.; Härkönen, P.; Isomaa, V.; Kaija, H.; Kurkela, R.; Li., Y.; Pulkka, A. Control of Cell Proliferation by Steroids: The Role of 17β-HSDs Mol. Cell. Endocrinol. 2006, 248, 141-148
9. Luu-The, V.; Zhang, Y.; Poirier, D.; Labrie, F. Characteristics of Human Types 1, 2 and 3 17β-Hydroxysteroid Dehydrogenase Activities: Oxidation/ Reduction and Inhibition J. Steroid Biochem. Mol. Biol. 1995, 55, 581-587
10. Lukacik, P.; Kavanagh, K. L.; Opperrmann, U. Structure and Function of Human 17β-Hydroxysteroid Dehydrogenases Mol. Cell. Endocrinol. 2006, 248, 61-71
11. Peltoketo, H.; Isomaa, V.; Mäentausta, O.; Vihko, R. Complete Amino-Acid Sequence of Human Placental 17β-Hydroxysteroid Dehydrogenase Deduced from cDNA FEBS Lett. 1988, 239, 73-77
12. Ghosh, D.; Pletnev, V. Z.; Zhu, D. W.; Wawrzak, Z.; Duax, W. L.; Pangborn, W.; Labrie, F.; Lin, S. X. Structure of Human Estrogenic 17β-Hydroxysteroid Dehydrogenase at 2.20 A Resolution Structure 1995, 3, 503-513
13. Azzi, A.; Rehse, P. H.; Zhu, D. W.; Campbell, R. L.; Labrie, F.; Lin, S. X. Crystal Structure of Human Estrogenic 17β-Hydroxysteroid Dehydrogenase Complexed with 17β-Estradiol Nat. Struct. Biol. 1996, 3, 665-668
14. Lin, S. X.; Yang, F.; Jin, J. Z.; Breton, R.; Zhu, D. W.; Luu-The, V.; Labrie, F. Subunit Identity of the Dimeric 17β-Hydroxysteroid Dehydrogenase from Human Placenta J. Biol. Chem. 1992, 267, 16182-16187
15. + Identifies Two Principal Targets for the Design of Inhibitors Structure 1996, 3, 905-915
16. Shayamala, G.; Chou, Y. C.; Cardiff, R. D.; Vargis, E. Effect of c-neu/ ErbB2 Expression Levels on Estrogen Receptor α-Dependent Proliferation in Mammary Epithelial Cells: Implications for Breast Cancer Biology Cancer Res. 2006, 66, 10391-10398
17. Lee, Y. R.; Park, J.; Yu, H. N.; Kim, J. S.; Youn, H. J.; Jung, S. H. Up-Regulation of PI3K/Akt Signaling by 17β-Estradiol Through Activation of Estrogen Receptor-α, but not Estrogen Receptor-β, and Stimulates Cell Growth in Breast Cancer Cells Biochem. Biophys. Res. Commun. 2005, 336, 1221-1226
18. Peltoketo, H.; Luu-The, V.; Simard, J.; Adamski, J. 17β- Hydroxysteroid Dehydrogenase (HSD)/17-Ketosteroid Reductase (KSR) Family; Nomenclature and Main Characteristics of the 17HSD/KSR Enzymes J. Mol. Endocrinol. 1999, 23, 1-11
19. Sawetawan, C.; Milewicha, L.; Worda, R. A.; Carra, B. R.; Rainey, W. E. Compartmentalization of Type 1 17β-Hydroxysteroid Oxidoreductase in the Human Ovary Mol. Cell. Endocrinol. 1994, 94, 161-168
20. Fournet-Dulguerov, N.; MacLusky, N. J.; Leranth, C. Z.; Todd, R.; Mendelson, C. R.; Simpson, E. R.; Naftolin, F. Immunohistochemical Localization of Aromatase Cytochrome P-450 and Estradiol Dehydrogenase in the Syncytiotrophoblast of the Human Placenta J. Clin. Endocrinol. Metab. 1987, 65, 757-764
21. Sasano, H.; Frost, A. R.; Saitoh, R.; Harada, N.; Poutanen, M; Vihko, R.; Bulun, S. E.; Silverberg, S. G.; Nagura, H. Aromatase and 17-Beta- Hydroxysteroid Dehydrogenase Type 1 in Human Breast Carcinoma J. Clin. Endocrinol. Metab. 1996, 81, 4042-4046
22. Dassen, H.; Punyadeera, C.; Kamps, R.; Delvoux, B.; Van Langendonckt, A.; Donnez, J.; Husen, B.; Thole, H.; Dunselman, G.; Groothuis, P. Estrogen-Metabolizing Enzymes in Endometrium and Endometriosis Hum. Reprod. 2007, 22, 3148-3158
23. Mueck, A. O.; Seeger, H.; Wallwiener, D. Comparison of the Proliferative Effects of Estradiol and Conjugated Equine Estrogens on Human Breast Cancer Cells and Impact of Continuous Combined Progestogen Addition Climacteric 2003, 6, 221-227
24. Miyoshi, Y.; Ando, A.; Shiba, E.; Taguchi, T.; Tamaki, Y.; Noguchi, S. Involvement of Up-Regulation of 17β-Hydroxysteroid Dehydrogenase Type 1 in Maintenance of Intratumoral High Estradiol Levels in Postmenopausal Breast Cancers Int. J. Cancer 2001, 94, 685-689
25. Gunnarsson, C.; Hellqvist, E.; Stal, O. 17β-Hydroxysteroid Dehydrogenases Involved in Local Oestrogen Synthesis Have Prognostic Significance in Breast Cancer Br. J. Cancer 2005, 92, 547-552
26. Sasano, H.; Suzuki, T.; Miki, Y.; Moriya, T. Intracrinology of Estrogens and Androgens in Breast Carcinoma J. Steroid Biochem. Mol. Biol. 2008, 108, 181-185
27. Miki, Y.; Suzuki, T.; Sasano, H. Intracrinology of Sex Steroids in Ductal Carcinoma in situ (DCIS) of Human Breast: Comparison to Invasive Ductal Carcinoma (IDC) and Non-Neoplastic Breast J. Steroid Biochem. Mol. Biol. 2009, 114, 68-71
28. Picard, F.; Schulz, T.; Hartmann, R. W. 5-Phenyl Substituted 1-Methyl-2-pyridones and 4′-Substituted Biphenyl-4-carboxylic Acids. Synthesis and Evaluation as Inhibitors of Steroid-5α-reductase Type 1 and 2 Bioorg. Med. Chem. 2002, 10, 437-448
29. Baston, E.; Hartmann, R. W. N-Substituted 4-(5-Indolyl) Benzoic Acids. Synthesis and Evaluation of Steroid 5α-Reductase Type I and II Inhibitory Activity Bioorg. Med. Chem. Lett. 1999, 9, 1601-1606
30. Baston, E.; Palusczak, A.; Hartmann, R. W. 6-Substituted 1H-Quinolin-2-ones and 2-Methoxy-Quinolined: Synthesis and Evaluation as Inhibitors of Steroid 5α Reductases Types 1 and 2 Eur. J. Med. Chem. 2000, 35, 931-940
31. Mazumdar, M.; Fournier, D.; Zhu, D. W.; Cadot, C.; Poirier, D.; Lin, S. X. Binary and Ternary Crystal Structure Analyses of a Novel Inhibitor with 17βHSD Type 1: a Lead Compound for Breast Cancer Therapy Biochem. J. 2009, 424, 357-366
32. Kruchten, P.; Werth, R.; Marchais-Oberwinkler, S.; Frotscher, M.; Hartmann, R. W. Development of a Biological Screening System for the Evaluation of Highly Active and Selective 17β-HSD1 Inhibitors as Potential Therapeutic Targets Mol. Cell. Endocrinol. 2009, 301, 154-157
33. Vihko, P.; Isomaa, V.; Ghosh, D. Structure and Function of 17β-Hydroxysteroid Dehydrogenase Type 1 and Type 2 Moll. Cell. Endocrinol. 2001, 171, 71-76
34. Oduwole, O. O.; Isomaa, V. V.; Nokelainen, P.; Stenbäck, F.; Vihko, P. T. Down-Regulation of Estrogen Metabolizing 17β-Hydroxysteroid Dehydrogenase Type 2 Expression Correlates Inversly with Ki67 Proliferation Marker in Colon Cancer Development Int. J. Cancer 2002, 97, 1-6
35. Day, J.; Tutill, H. J.; Newman, S. P.; Purohit, A.; Lawrence, H. R.; Vicker, N.; Potter, B. V. L.; Reed, M. J. 17β-Hydroxysteroid Dehydrogenase Type 1 and Type 2: Association Between mRNA Expression and Activity in Cell Lines Mol. Cell. Endocrinol. 2006, 248, 246-249
36. Penning, T. M. 17β-Hydroxysteroid Dehydrogenase: Inhibitors and Inhibitor Design Endocr. Relat. Cancer 1996, 3, 41-56
37. Poirier, D. Inhibitors of 17β-Hydroxysteroid Dehydrogenases Curr. Med. Chem. 2003, 10, 453-477
38. Brožič, P.; Lanišnik Rižner, T.; Gobec, S. Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 Curr. Med. Chem. 2008, 10, 137-150
39. Messinger, J.; Husen, B.; Koskimies, P.; Hirvelä, L.; Kallio, L.; Saaranketo, P.; Thole, H. Estrone C15 Derivatives - A New Class of 17β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors Mol. Cell. Endocrinol. 2009, 301, 216-224
40. Mesinger, J.; Hirvelä, L.; Husen, B.; Kangas, L.; Koskimies, P.; Pentikäinen, O.; Saaraenketo, P.; Thole, H. New Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 Mol. Cell. Endocrinol. 2006, 248, 192-198
41. Lilienkampf, A.; Karkola, S.; Alho-Richmond, S.; Koskimies, P.; Johansson, N.; Huhtinen, K.; Vihko, K.; Wähäla, K. Synthesis and Biological Evaluation of 17β-hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) Inhibitors Based on a Thieno[2,3- d ]pyrimidin-4(3H)-one Core J. Med. Chem. 2009, 52, 6660-6671
42. Bey, E.; Marchais-Oberwinkler, S.; Werth, R.; Negri, M.; Al-Soud, Y. A.; Kruchten, P.; Oster, A.; Frotscher, M.; Birk, B.; Hartmann, R. W. Design, Synthesis, Biological Evaluation and Pharmacokinetics of Bis(hydroxyphenyl) Substituted Azoles, Thiophenes, Benzenes, and Aza-Benzenes as Potent and Selective Nonsteroidal Inhibitors of 17 β -Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) J. Med. Chem. 2008, 51, 6725-6739
43. Bey, E.; Marchais-Oberwinkler, S.; Negri, M.; Kruchten, P.; Oster, A.; Klein, T.; Spadaro, A.; Werth, R.; Frotscher, M.; Birk, B.; Hartmann, R. W. New Insights into the SARs and Binding Modes of Bis(hydroxyphenyl)thiophenes and -bezenes: Influence of Additional Substituents on 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) Inhibitory Activity and Selectivity J. Med. Chem. 2009, 51, 6724-6743
44. Kruchten, P.; Werth, R.; Bey, E.; Oster, A.; Marchais-Oberwinkler, S.; Frotscher, M.; Hartmann, R. W. Selective Inhibition of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) Reduces Estrogen Responsive Cell Growth of T47-D Breast Cancer Cells J. Steroid Biochem. Mol. Biol. 2009, 114, 200-206
45. Frotscher, M.; Ziegler, E.; Marchais-Oberwinkler, S.; Kruchten, P.; Neugebauer, A.; Fetzer, L.; Scherer, C.; Müller-Vieira; Messinger, J.; Thole, H.; Messinger, J.; Hartmann, R. W. Design, Synthesis, and Biological Evaluation of (Hydroxyphenyl)naphthalene and -quinoline Derivatives: Potent and Selective Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) for the Treatment of Estrogen-Dependent Diseases J. Med. Chem. 2008, 51, 2158-2169 (Pubitemid 351503271)
46. Marchais-Oberwinkler, S.; Frotscher, M.; Ziegler, E.; Werth, R.; Kruchten, P.; Messinger, J.; Thole, H.; Hartmann, R. W. Structure-Activity Study in the Class of 6-(3′-Hydroxyphenyl)napthalenes Leading to an Optimization of a Pharmacophore Model for 17β-Hydroxysteroid Dehydrogenase Type 1 (17 β -HSD1) Inhibitors Mol. Cell. Endocrinol. 2009, 301, 205-211
47. Oster, A.; Klein, T.; Werth, R.; Kruchten, P.; Bey, E.; Negri, M.; Marchais-Oberwinkler, S.; Frotscher, M.; Hartmann, R. W. Novel Estrone Mimetics with High 17β-HSD1 Inhibitory Activity Bioorg. Med. Chem. 2010, 18, 3494-3505
48. Wu, L.; Wang, X.; Xu, V.; Farzaneh, F.; Xu, R. The Structure and Pharmacological Functions of Coumarins and Their Derivatives Curr. Med. Chem. 2006, 16, 4236-4260
49. Brožič, P.; Kocbek, P.; Sova, M.; Kristl, J.; Martens, S.; Adamski, J.; Gobec, S.; Lanišnik Rižner, T. Flavanoids and Cinnamic Acid Derivatives as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 Mol. Cell. Endocrinol. 2008, 301, 229-234
50. Milligan, S. R.; Balasubramanian, A. V.; Kalita, J. C. Relative Potency of Xenobiotic Estrogens in an Acute in Vivo Mammalian Assay Environ. Health Perspect. 1998, 106, 23-26
51. Miyaura, N.; Suzuki, A. The Palladium Catalyzed Cross-Coupling Reaction of Phenylboronic Acid with Haloarenes in the Presence of Bases Synth. Commun. 1981, 11, 513-519
52. Brousmiche, D. W.; Xu, M.; Lukeman, M.; Wan, P. Photohydration and Photosolvolysis of Biphenyl Alkenes and Alcohols via Biphenyl Quinone Methide-Type Intermediates and Diarylmethyl Carbocations J. Am. Chem. Soc. 2003, 125, 12961-12970
53. Brunet, E.; Alonso, M. T.; Juanes, O.; Velasco, O.; Rodriguez-Ubis, J. C. Novel Polyaminocarboxylate Chelates Derived from 3-Aroylcoumarins Tetrahedron 2008, 57, 3105-3116
54. Hutschenreuter Tilman, U.; Ehmer, P. B.; Hartmann, R. W. Synthesis of Hydroxy Derivatives of Highly Potent Non-Steroidal CYP 17 Inhibitors as Potential Metabolites and Evaluation of Their Activity by a Non-Cellular Assay Using Recombinant Human Enzyme J. Enzyme. Inhib. Med. Chem. 2004, 19, 17-32
55. Mewshaw, R. E.; Edsall, R. J., Jr.; Yang, C.; Manas, E. S.; Xu, Z. B.; Henderson, R. A.; Keith, J. C., Jr.; Harris, H. A. ER β Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold to Achieve ERβ Selectivity J. Med. Chem. 2005, 48, 3953-3979
56. Horning, E. C.; Horning, M. G.; Dimmig, D. A. 3-Carbethoxycoumarin 2H-1-Benzopyran-3-Carboxylic Acid, 2-Oxo, Ethyl Ester Org. Synth. 1955, 3, 165
57. Harayama, T.; Katsuno, K.; Hirami, N.; Masako, F.; Nishita, Y.; Ishii, H.; Kaneko, Y. A Convenient Synthesis of a Simple Coumarin from Salicylaldehyde and Wittig Reagent (I): A Synthesis of Methoxy and Hydroxycoumarins Heterocycles 1994, 39, 613-622
58. Haight, A. R.; Bailey, A. E.; Baker, W. S.; Cain, M. H.; Copp, R. R.; DeMattei, R. A.; Ford, K. L.; Henry, R. F.; Hsu, M. C.; Keyes, R. F.; King, S. A.; McLaughlin, L. A.; Melcher, L. M.; Nadler, W. R.; Oliver, P. A.; Parekh, S. I.; Patel, H. H.; Seif, L. S.; Staeger, M. A.; Wayne, G. S.; Wittenberger, S. J.; Zhang, W. A Scalable Synthesis of Fiduxosin Org. Process Res. Dev. 2004, 8, 897-902
59. + Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 840-845
60. 50) of an Enzymatic Reaction Biochem. Pharmacol. 1973, 22, 3099-3108
61. Zimmermann, J.; Liebl, R.; von Angerer, E. 2,5-Diphenylfuran-Based Pure Anti-Estrogens with Selectivity for the Estrogen Receptor Alpha J. Steroid Biochem. Mol. Biol. 2005, 94, 57-66
62. Bhavnani, B. R.; Tam, S. P.; Lu, X. F. Structure-Activity Relationships and Differential Interactions and Functional Activity of Various Equine Estrogens Mediated via Estrogen Receptors (ERs) ERα and ERβ Endocrinology 2008, 149, 4857-4870
63. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A Fast Flexible Docking Method using an Incremental Construction Algorithm J. Mol. Biol. 1996, 261, 470
64. Mazza, C. Thesis. Universite Joseph Fourier, 1997.
65. + in 17β-Hydroxysteroid Dehydrogenase J. Biol. Chem. 1998, 273, 8145-8152
66. Puranen, T.; Poutanen, M.; Ghosh, D.; Vihko, P.; Vihko, R. Characterization of Structural and Functional Properties of Human 17β-Hydroxysteroid Dehydrogenase Type 1 Using Recombinant Enzymes and Site-Directed Mutagenesis Mol. Endocrinol. 1997, 11, 77-86
67. Huang, Y. W.; Pineau, I.; Chang, H. J.; Azzi, A.; Bellemare, V.; Laberge, S.; Lin, S. X. Critical Residues for the Specificity of Cofactors and Substrates in Human Estrogenic 17β-Hydroxysteroid Dehydrogenase 1: Variants Designed from the Three-Dimensional Structure of the Enzyme Mol. Endocrinol. 2001, 15, 2010-2020
68. The PyMOL Molecular Graphics System, Version 1.3, Schrödinger, LLC.
69. Grant, J. A.; Gallardo, M. A.; Pickup, B. J. Comput. Chem. 1996, 17, 1653
70. Tanrikulu, Y; Nietert, M; Scheffer, U; Proschak, E; Grabowski, K; Schneider, P; Weidlich, M; Karas, M; Goebel, M; Schneider, G. Scaffold hopping by "fuzzy" pharmacophores and its application to RNA targets ChemBioChem 2007, 8, 1932-6