Effects of altering the electronics of 2-methoxyestradiol on cell proliferation, on cytotoxicity in human cancer cell cultures, and on tubulin polymerization

Journal of Medicinal Chemistry

Volumn 47, Issue 21, 2004, Pages 5126-5139

  Edsall, Allison B ^a   Mohanakrishnan, Arasambattu K ^a   Yang, Donglai ^a   Fanwick, Philip E ^b   Hamel, Ernest ^c   Hanson, Arthur D ^d   Agoston, Gregory E ^d   Cushman, Mark ^a  

^a PURDUE UNIVERSITY   (United States)

^b PURDUE UNIVERSITY   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

^d ENTREMED INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

17,17 DIFLUORO 2 METHOXY 1,3,5(10)ESTRATRIEN 3 OL; 17,17 DIFLUORO BETA ESTRA 1,3,5(10)TRIEN 3 OL; 17ALPHA METHYL BETA ESTRADIOL; 17BETA HYDROXYPHENYLMETHYL 2 METHOXY 17ALPHA METHYL 1,3,5(10)ESTRATRIEN 3 OL; 2 (1' KETOPROPYL) 17BETA ESTRADIOL; 2 (1',1' DIFLUOROETHYL)BETA ESTRADIOL 3,17 DIACETATE; 2 (2' HYDROXYIMINOPROPYLOXY)ESTRADIOL; 2 (3 N,N DIMETHYLAMINOPROPYL)IMINOMETHYLESTRADIOL; 2 ACETYL BETA ESTRADIOL; 2 ALLYL BETA ESTRADIOL; 2 CYCLOPROPYLIMINOMETHYLESTRADIOL; 2 ETHOXY 17 (1' METHYLENE)ESTRA 1,3,5(10)TRIEN 3 OL; 2 ETHOXY 17 (1' METHYLENE)ESTRA 1,3,5(10)TRIENE 3 OL; 2 ETHOXY 17ALPHA METHYLESTRADIOL; 2 METHOXY 17ALPHA METHYL BETA ESTRADIOL; 2 METHOXY 17ALPHA TRIFLUOROMETHYL BETA ESTRADIOL; 2 METHOXYESTRADIOL; 2 METHOXYMETHYL BETA ESTRADIOL; 2 PENTAFLUOROETHYL BETA ESTRADIOL; 2 PROPYNYL 17ALPHA METHYLESTRADIOL; ESTRADIOL DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXICITY; DRUG STABILITY; ELECTRICITY; HUMAN; HUMAN CELL; IC 50; MICROTUBULE ASSEMBLY; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; BIOPOLYMERS; CELL DIVISION; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; DRUG SCREENING ASSAYS, ANTITUMOR; ESTRADIOL; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP; TUBULIN;

EID: 4744371076     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049647a     Document Type: Article

References (37)

1. Fishman, J. A. Aromatic Hydroxylation of Estrogens. Annu. Rev. Physiol. 1983, 45, 61-72.
2. Breuer, H.; Knuppen, R. Biogenesis of 2-Methoxyestradiol-17β in Human Liver. Naturwissenschaften 1960, 47, 280-281.
3. Gelbke, H. P.; Knuppen, R. The Excretion of Five Different 2-Hydroxyestrogen Monomethyl Ethers in Human Pregnancy Urine. J. Steroid Biochem. 1976, 7, 457-463.
4. Fotsis, T.; Zhang, Y.; Pepper, M. S.; Adlercreutz, H.; Montesano, R.; Nawroth, P. P.; Schweigerer, L. The Endogenous Estrogen Metabolite 2-Methoxyestradiol Inhibits Angiogenesis and Suppresses Tumor Growth. Nature 1994, 368, 237-239.
5. Seegers, J. C.; Aveling, M.-L.; van Aswegen, C. H.; Cross, M.; Koch, F.; Joubert, W. S. The Cytotoxic Effects of Estradiol-17,8, Catecholestradiols and Methoxyestradiols on Dividing MCF-7 and HeLa Cells. J. Steroid Biochem. 1989, 32, 797-809.
6. Lottering, M.-L.; Haag, M.; Seegers, J. C. Effects of 17β-Estradiol Metabolites on Cell Cycle Events in MCF-7 Cells. Cancer Res. 1992, 52, 2, 5926-5932.
7. Sledge, G. W. J.; Miller, K. D.; Haney, L. G.; Nguyen, D. D.; Storniolo, A. M.; Phillips, E. N.; Pribluda, V.; Gubish, E. R. A phase I study of 2-methoxyestradiol (2ME2) in patients (pts) with refractory metastatic breast cancer (MBC). Presented at the ASCO Annual Meeting, Orlando, FL, 2002.
8. Miller, K. D.; Murry, D. J.; Curry, E.; Haney, L. G.; McClaskey, N.; Storniolo, A. M.; Phillips, E.; Pribluda, V.; Gubish, E. R.; Sledge, G. W. A phase I study of 2-methoxyestradiol (2ME2) plus docetaxel in patients with metastatic breast cancer. Presented at the ASCO Annual Meeting, Orlando, FL, 2002.
9. Wilding, G.; Sweeney, C.; King, D. M.; Horvath, D.; Staab, M. J.; Fife, K.; Armstrong, V.; Sorioano, J. V.; Pribluda, V. S.; Gubish, E. R.; Sidor, C. Phase 2, multicenter, randomized, double-blind, safety, pharmacokinetic, pharmacodynamic, and efficacy study of two doses of 2-methoxyestradiol administered orally in patients with hormone refractory prostate cancer. Presented at the ASCO Annual Meeting, Orlando, FL, 2002.
10. D'Amato, R. J.; Lin, C. M.; Flynn, E.; Folkman, J.; Hamel, E. 2-Methoxyestradiol, an Endogenous Mammalian Metabolite, Inhibits Tubulin Polymerization by Interacting at the Colchicine Site. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 3964-3968.
11. Hamel, E.; Lin, C. M.; Flynn, E.; D'Amato, R. J. Interactions of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite, with Unpolymerized Tubulin and with Tubulin Polymers. Biochemistry 1996, 35, 1304-1310.
12. Mabjeesh, N. J.; Escuin, D.; LaVallee, T. M.; Pribluda, V. S.; Swartz, G. M.; Johnson, M. S.; Willard, M. T.; Zhong, H.; Simons, J. W.; Giannakakou, P. 2ME2 Inhibits Tumor Growth and Angiogenesis by Disrupting Microtubules and Dysregulating HIF. Cancer Cell 2003, 3, 363-375.
13. Martucci, C. P. Metabolic Fate of Catechol Estrogens. In Catechol Estrogens; Merriam, G. R.; Lipsett, M. B., Eds.; Raven Press: New York, 1983; pp 115-121.
14. Ball, P.; Hoppen, H.-O.; Knuppen, R. Metabolism of Oestradiol-17β and 2-Hydroxyestradiol-17β in Rat Liver Slices. Hoppe-Seyler's Z. Physiol. Chem. 1973, 354, 771-780.
15. Ball, P.; Stubenrauch, G.; Knuppen, R. Metabolism of 2-Methoxy-and 4-Methoxyestrone in Man In Vivo. J. Steroid Biochem. 1977, 8, 989-993.
16. Mobley, J. A.; Bhat, A. S.; Brueggemeier, R. W. Measurement of the Oxidative DNA Damage by Catechol Estrogens and Analogues In Vitro. Chem. Res. Toxicol. 1999, 12, 270-277.
17. Cavalieri, E. L.; Stack, D. E.; Devanesan, P. D.; Todorovic, R.; Dwivedy, I.; Higginbotham, S.; Johansson, S. L.; Patil, K. D.; Gross, M. L.; Gooden, J. K.; Ramanathan, R.; Cerny, R. L.; Rogan, E. G. Molecular Origin of Cancer: Catechol Estrogen-3,4-quinones as Endogenous Tumor Initiators. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 10937-10942.
18. Miller, T. A.; Bulman, A. L.; Thompson, C. D.; Garst, M. E.; Macdonald, T. L. The Synthesis and Evaluation of Functionalized Estratropones: Potent Inhibitors of Tubulin Polymerization. Bioorg., Med. Chem. Lett. 1997, 7, 1851-1856.
19. Miller, T. A.; Bulman, A. L.; Thompson, C. D.; Garst, M. E.; Macdonald, T. L. Synthesis and Structure - Activity Profiles of A-Homoestranes, the Estratropones. J. Med. Chem. 1997, 40, 3836-3841.
20. Cushman, M.; He, H.-M.; Katzenellenbogen, J.; Varma, R. K.; Hamel, E.; Lin, C. M.; Ram, S.; Sachdeva, Y. P. Synthesis of Analogues of 2-Methoxyestradiol with Enhanced Inhibitory Effect on Tubulin Polymerization and Cancer Cell Growth. J. Med. Chem. 1997, 40, 2323-2334.
21. Cushman, M.; He, H.-M.; Katzenellenbogen, J. A.; Lin, C.; Hamel, E. Synthesis, Antitubulin and Antimitotic Activity, and Cytotoxicity of Analogues 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.
22. Cushman, M.; Mohanakrishnan, A. K.; Hollingshead, M.; Hamel, E. The Effect of Exchanging Various Substituents at the 2-Position of 2-Methoxyestradiol on Cytotoxicity in Human Cancer Cell Cultures and Inhibition of Tubulin Polymerization. J. Med. Chem. 2002, 45, 4748-4754.
23. Rao, P. N.; Cessac, J. W.; Tinley, T. L.; Mooberry, S. L. Synthesis and Antimitotic Activity of Novel 2-Methoxyestradiol Analogs. Steroids, 2002, 67, 1079-1089.
24. Mohanakrishnan, A. K.; Cushman, M. S. Pd(0)-Mediated Cross Coupling of 2-Iodoestradiol with Organozinc Bromides: A General Route to the Synthesis of 2-Alkynyl, 2-Alkenyl and 2-Alkylestradiol Analogues. Synlett 1999, 7, 1097-1099.
25. Lovely, C. J.; Brueggemeier, R. W. Synthesis of 2-Substituted Hydroxyalkyl and Aminoalkyl Estradiols. Tetrahedron Lett. 1994, 35, 8735-8738.
26. Brueggemeier, R, W.; Bhat, A, S.; Lovely, C. J.; Coughenour, H. D.; Joomprabutra, S.; Weitzel, D. H.; Vandre, D. D.; Yusuf, F.; Burak, W. E. 2-Methoxymethylestradiol: a New 2-Methoxy Estrogen Analog that Exhibits Antiproliferative Activity and Alters Tubulin Dynamics. J. Steroid Biochem. Mol. Biol. 2001, 78, 145-156.
27. Pert, D. J.; Ridley, D. D. Formylation of Estrogens. Aust. J. Chem. 1989, 42, 405-419.
28. Lovely, C. J.; Gilbert, N. E.; Liberto, M. M.; Sharp, D. W.; Lin, Y. C.; Brueggemeier, R. W. 2-(Hydroxyalkyl)estradiols: Synthesis and Biological Evaluation. J. Med. Chem. 1998, 39, 1917-1923.
29. Wang, Z.; Cushman, M. An Optimized Synthesis of 2-Methoxyestradiol, a Naturally Occurring Human Metabolite with Anticancer Activity. Synth. Commun. 1998, 28, 4431-4437.
30. Boyd, M. R.; Paull, K. D. Some Practical Considerations and Applications of the National Cancer Institute In Vitro Anticancer Drug Discovery Screen. Drug Dev. Res. 1995, 34, 91-109.
31. Fukuda, H.; Kitazume, T. A General Route to N′-(2,2-Difluoro-3- hydroxyalkanoyl)nornicotines. J. Fluorine Chem. 1995, 74, 171-176.
32. Ryberg, P.; Matsson, O. The Mechanism of Base-Promoted HF Elimination from 4-Fluoro-4-(4-nitrophenyl)butan-2-one Is E1cB. Evidence from Double Isotopic Fractionation Experiments J. Org. Chem. 2002, 67, 811-814.
33. Hamel, E.; Lin, C. M. Separation of Active Tubulin and Microtubule-Associated Proteins by Ultracentrifugation and Isolation of a Component Causing the Formation of Microtubule Bundles. Biochemistry 1984, 23, 4173-4184.
34. Holton, P. G. Steroids. CLXXVI. Claisen Rearrangement of Estrone Allyl Ether. J. Org. Chem. 1962, 27, 357-361.
35. Farkas, E.; Bach, N. J. Catalytic Dehydrogenation of Estr-4-en-3-ones. J. Org. Chem. 1971, 36, 2715-2717.
36. Nambara, T.; Homma, S.; Akiyama, S. Analytical Chemical Studies on Steroids. XXXIII. Steroid Conjugates. III. New Synthesis of 2-Methoxyestrogens. Chem. Pharm. Bull. 1970, 18, 474-480.
37. Burla, M. C.; Camilli, M.; Carrozzini, B.; Cascarano, G. L.; Giacovazzo, C.; Polidori, G.; Spagna, R. SIR88 - a Direct-Methods Program for the Automatic Solution of Crystal Structures. J. Appl. Crystallogr. 2003, 36, 1103.