Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents

Journal of Medicinal Chemistry

Volumn 51, Issue 5, 2008, Pages 1295-1308

  Leese, Mathew P ^a   Jourdan, Fabrice L ^a   Gaukroger, Keira ^a   Mahon, Mary F ^b   Newman, Simon P ^c   Foster, Paul A ^c   Stengel, Chloe ^c   Regis Lydi, Sandra ^d   Ferrandis, Eric ^d   Di Fiore, Anna ^e   De Simone, Giuseppina ^e   Supuran, Claudiu T ^f   Purohit, Atul ^c   Reed, Michael J ^c   Potter, Barry V L ^a  

^a UNIVERSITY OF BATH   (United Kingdom)

^b University of Bath   (United Kingdom)

^c ST MARY S HOSPITAL   (United Kingdom)

^d IPSEN   (France)

^e CNR   (Italy)

^f UNIVERSITY OF FLORENCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHOXY 17 BETA CYANOMETHYL ESTRA 1,2,5(10)TRIEN 3 OL; 3 METHOXY 3 O SULFAMOYL 17BETA CYANOMETHYL ESTRA 1,2,5(10)TRIENE; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; CARBONATE DEHYDRATASE II; STERYL SULFATASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ARTICLE; CELL PROLIFERATION; CELL STRAIN MCF 7; CONTROLLED STUDY; CRYSTALLOGRAPHY; DRUG MECHANISM; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; HYDROGEN BOND; MICROTUBULE; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; CARBONIC ANHYDRASE II; CARBONIC ANHYDRASE INHIBITORS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; DRUG SCREENING ASSAYS, ANTITUMOR; ESTRADIOL; ESTRENES; FEMALE; HUMANS; MICE; MICE, NUDE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; NEOPLASM TRANSPLANTATION; NITRILES; STEREOISOMERISM; STERYL-SULFATASE; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSPLANTATION, HETEROLOGOUS; TUBULIN MODULATORS;

EID: 41649119942     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701319c     Document Type: Article

References (46)

1. Folkman, J.; Bach, M.; Rowe, J. W.; Davidoff, F.; Lambert, P.; Hirsch, C.; Goldberg, A.; Hiatt, H. H.; Glass, J.; Henshaw, E. Tumor angiogenesis: therapeutic implications. New Engl. J. Med. 1971, 285, 1182-1186.
2. Ferrara, N.; Kerbel, R. S. Angiogenesis as a therapeutic target. Nature 2005, 438, 967-974.
3. Ferrara, N.; Hillan, K. J.; Gerber, H. P.; Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discovery 2004, 3, 391-400.
4. Hurwitz, H.; Fehrenbacher, L.; Novotny, W.; Cartwright, T.; Hainsworth, J.; Heim, W.; Berlin, J.; Baron, A.; Griffing, S.; Holmgren, E.; Ferrara, N.; Fyfe, G.; Rogers, B.; Ross, R.; Kabbinavar, F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl. J. Med. 2004, 350, 2335-2342.
5. Jain, R. K.; Duda, D. G.; Clark, J. W.; Loeffler, J. S. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin. Pract. Oncol. 2006, 3, 24-40.
6. Leese, M. P.; Hejaz, H. A. M.; Mahon, M. F.; Newman, S. P.; Purohit, A.; Reed, M.; Potter, B. V. L. A-ring substituted estrogen sulfamates: Potent multi-targeted anti-cancer agents. J. Med. Chem. 2005, 48, 5243-5256.
7. Leese, M. P.; Newman, S. P.; Purohit, A.; Reed, M. J.; Potter, B. V. L. 2-Alkylsulfanyl estrogen derivatives: synthesis of a novel class of multi-targeted anti-tumor agents. Bioorg. Med. Chem. Lett. 2004, 14, 3135-3138.
8. Leese, M. P.; Leblond, B.; Newman, S. P.; Purohit, A.; Reed, M. J.; Potter, B. V. L. Anti-cancer activities of novel D-ring modified 2-substituted estrogen-3-O-sulfamates. J. Steroid Biochem. Mol. Biol. 2005, 94, 239-251.
9. Leese, M. P.; Leblond, B.; Smith, A.; Newman, S. P.; Di Fiore, A.; de Simone, G.; Supuran, C. T.; Purohit, A.; Reed, M. J.; Potter, B. V. L. 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents: Synthesis, in vitro SAR, protein crystallography, and in vivo activity. J. Med. Chem. 2006, 49, 7683-7696.
10. Purohit, A.; Hejaz, H. A. M.; Walden, L.; MacCarthy-Morrogh, L.; Packham, G.; Potter, B. V. L.; Reed, M. J. The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours. Int. J. Cancer 2000, 85, 584-589.
11. MacCarthy-Morrogh, L.; Townsend, P. A.; Purohit, A.; Hejaz, H. A. M.; Potter, B. V. L.; Reed, M. J.; Packham, G. Differential effects of estrone and estrone-3-O-sulfamate derivatives on mitotic arrest, apoptosis, and microtubule assembly in human breast cancer cells. Cancer Res. 2000, 60, 5441-5450.
12. Newman, S. P.; Leese, M. P.; Purohit, A.; James, D. R. C.; Rennie, C. E.; Potter, B. V. L.; Reed, M. J. Inhibition of in vitro angiogenesis by 2-methoxy- and 2-ethyl-estrogen sulfamates. Int. J. Cancer 2004, 109, 533-540.
13. Chander, S. K.; Foster, P. A.; Leese, M. P.; Newman, S. P.; Potter, B. V. L.; Purohit, A.; Reed, M. J. In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol. Br. J. Cancer 2007, 96, 1368-1376.
14. Wood, L.; Leese, M. P.; Mouzakiti, A.; Purohit, A.; Potter, B. V. L.; Reed, M. J.; Packham, G. 2-MeOE2bisMATE induces caspase-dependent apoptosis in CAL51 breast cancer cells and overcomes resistance to TRAIL via cooperative activation of caspases. Apoptosis 2004, 9, 323-332.
15. Newman, S. P.; Ireson, C. R.; Tutill, H. J.; Day, J. M.; Parsons, M. F. C.; Leese, M. P.; Potter, B. V. L.; Reed, M. J.; Purohit, A. The role of 17β-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer. Cancer Res. 2006, 66, 324-330.
16. Ireson, C. R.; Chander, S. K.; Purohit, A.; Perera, S.; Newman, S. P.; Parish, D.; Leese, M. P.; Smith, A. C.; Potter, B. V. L.; Reed, M. J. Pharmacokinetics and efficacy of 2-methoxyoestradiol and 2-methoxyoestradiol- bis-sulphamate in vivo in rodents. Br. J. Cancer 2004, 90, 932-937.
17. Reed, M. J.; Purohit, A.; Newman, S. P.; Potter, B. V. L. Steroid sulfatase: Molecular biology, regulation and inhibition. Endocr. Rev. 2005, 26, 171-202.
18. Reed, M. J.; Purohit, A.; Woo, L. W. L.; Potter, B. V. L. The development of steroid sulphatase inhibitors. Endocr.-Relat. Cancer 1996, 3, 9-23.
19. Ho, Y. T.; Purohit, A.; Vicker, N.; Newman, S. P.; Robinson, J. J.; Leese, M. P.; Ganeshapillai, D.; Woo, L. W. L.; Potter, B. V. L.; Reed, M. J. Inhibition of carbonic anhydrase II by steroidal and non-steroidal sulphamates. Biochem. Biophys. Res. Commun. 2003, 305, 909-914.
20. Stanway, S. J.; Purohit, A.; Woo, L. W. L.; Sufi, S.; Vigushin, D.; Ward, R.; Wilson, R.; Stanczyk, F. Z.; Dobbs, N.; Kulinkaya, E.; Elliott, M.; Potter, B. V. L.; Reed, M. J.; Coombs, R. C. Phase I study of STX64 (667 Coumate) in breast cancer patients: The first study of a steroid sulfatase inhibitor. Clin. Cancer Res. 2006, 12, 1585-1592.
21. Stanway, S. J.; Delavault, P.; Purohit, A.; Woo, L. W. L.; Thurieau, C.; Potter, B. V. L.; Reed, M. J. Steroid sulfatase: a new target for the endocrine therapy of breast cancer. Oncologist 2007, 12, 370-374.
22. Hussain, S. A.; Ganesan, R.; Reynolds, G.; Gross, L.; Stevens, A.; Pastorek, J.; Murray, P. G.; Perunovic, B.; Anwar, M. S.; Billingham, L.; James, N. D.; Spooner, D.; Poole, C. J.; Rea, D. W.; Palmer, D. H. Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer. Br. J. Cancer 2007, 96, 104-109.
23. Cushman, M.; He, H. M.; Katzenellenbogen, J. A.; Varma, R. K.; Hamel, E.; Lin, C. M.; Ram, S.; Sachdeva, Y. P. Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on tubulin polymerization and cancer cell growth. J. Med. Chem. 1997, 40, 2323-2334.
24. Klauber, N.; Parangi, S.; Flynn, E.; Hamel, E.; D'Amato, R. J. Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res. 1997, 57, 81-86.
25. Cushman, M.; He, H. M.; Katzenellenbogen, J. A.; Lin, C. M.; Hamel, E. Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicine binding site. J. Med. Chem. 1995, 38, 2041-2049.
26. Abbate, F.; Winum, J. Y.; Potter, B. V. L.; Casini, A.; Montera, J. L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid sulfatase. Bioorg. Med. Chem. Lett. 2004, 14, 231-234.
27. Elger, W.; Schwarz, S.; Hedden, A. M.; Reddersen, G.; Schneider, B. Sulfamates of various estrogens are prodrugs with increased systemic and reduced hepatic estrogenicity at oral application. J. Steroid Biochem. Mol. Biol. 1995, 55, 395-403.
28. Dahut, W. L.; Lakhani, N. J.; Gulley, J. L.; Arlen, P. M.; Kohn, E. C.; Kotz, H.; McNally, D.; Parr, A.; Nguyen, D.; Yang, S. X.; Steinberg, S. M.; Venitz, J.; Sparreboom, A.; Figg, W. D. Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors. Cancer Biol. Ther. 2006, 5, 22-27.
29. Sutherland, T. E.; Anderson, R. L.; Hughes, R. A.; Altmann, E.; Schuliga, M.; Ziogas, J.; Stewart, A. G. 2-Methoxyestradiol: a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents. Drug Discovery Today 2007, 12, 577-584.
30. Bubert, C.; Leese, M. P.; Mahon, M. F.; Ferrandis, E.; Regis-Lydi, S.; Kasprzyk, P. G.; Newman, S. P.; Ho, Y. T.; Purohit, A.; Reed, M. J.; Potter, B. V. L. 3,17-Disubstituted 2-alkylestra-1,3,5(10)-trien-3-ol derivatives: synthesis, in vitro and in vivo anti-cancer activity. J. Med. Chem. 2007, 50, 4443.
31. Okada, M.; Iwashita, S.; Koizumi, N. Efficient general method for sulfamoylation of a hydroxyl group. Tetrahedron Lett. 2000, 41, 7047-7051.
32. Burgess, E. M.; Penton, H. R.; Taylor, E. A. Synthetic applications of N-carboalkoxysulfamate esters. J. Am. Chem. Soc. 1970, 92, 5224-5226.
33. Ohira, S. Methanolysis of dimethyl(1-diazo-2-oxopropyl)phosphonate. Generation of (diazomethyl) phosphonate and reaction with carbonyl compounds. Synth. Commun. 1989, 19, 561-564.
34. Tinley, T. L.; Leal, R. M.; Randall-Hlubek, D. A.; Cessac, J. W.; Wilkens, L. R.; Rao, P. N.; Mooberry, S. L. Novel 2-methoxyestradiol analogues with antitumor activity. Cancer Res. 2003, 63, 1538-1549.
35. Boyd, M. R.; Pauli, K. D. Some practical consideration and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 1995, 34, 91-109.
36. Shoemaker, R. H. The NCI 60 human tumor cell line screen: An information-rich screen informing on mechanisms of toxicity. In Vitro Cell. Dev. Biol.: Anim. 2006, 42, 5A.
37. Newman, S. P.; Foster, P. A.; Ho, Y. T.; Day, J. M.; Raobaikady, B.; Kasprzyk, P. G.; Leese, M. P.; Potter, B. V. L.; Reed, M. J.; Purohit, A. The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disrupters as therapy for hormone-independent prostate and breast cancers. Br. J. Cancer 2007, 97, 1673-1682.
38. Purohit, A.; Williams, G. J.; Howarth, N. M.; Potter, B. V. L.; Reed, M. J. Inactivation of steroid sulfatase by an active site directed inhibitor, estrone-3-O-sulfamate. Biochemistry 1995, 34, 11508-11514.
39. Lloyd, M. D.; Thiyagarajan, N.; Ho, Y. T.; Woo, L. W. L.; Sutcliffe, O. B.; Purohit, A.; Reed, M. J.; Acharya, K. R.; Potter, B. V. L. First crystal structures of human carbonic anhydrase II in complex with dual aromatase-steroid sulfatase inhibitors. Biochemistry 2005, 44, 6858-6866.
40. Appel, R.; Berger, G. Uber das hydrazidosulfamid (On hydrazidosulfamide). Chem. Ber. 1958, 91, 1339-1341.
41. Woo, L. W. L.; Lightowler, M.; Purohit, A.; Reed, M. J.; Potter, B. V. L. Heteroatom-substituted analogues of the active-site directed inhibitor estra-1,3,5(10)-trien-17-one-3-sulphamate inhibit estrone sulphatase by a different mechanism. J. Steroid Biochem. Mol. Biol. 1996, 57, 79-88.
42. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Method Enzymol. 1997, 276, 307-326.
43. Eriksson, A. E.; Jones, T. A.; Liljas, A. Refined structure of human carbonic anhydrase II at 2.0Å resolution. Proteins 1988, 4, 274-282.
44. Brunger, A. T.; Adams, P. D.; Clore, G. M.; Delano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warren, G. L. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D 1998, 54, 905-921.
45. Jones, T. A.; Zou, J. Y.; Cowan, S. W.; Kjeldgaard, M. Improved methods for building protein models in electron-density maps and the location of errors in these models. Acta Crystallogr., Sect. A 1991, 47, 110-119.
46. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 1993, 26, 283-291.