Design, synthesis, and estrogenic activity of a novel estrogen receptor modulator - A hybrid structure of 17β-estradiol and vitamin E in hippocampal neurons

Journal of Medicinal Chemistry

Volumn 50, Issue 18, 2007, Pages 4471-4481

  Zhao, Liqin ^a   Jin, Chunyang ^b   Mao, Zisu ^a   Gopinathan, Madathil B ^b   Rehder, Kenneth ^b   Brinton, Roberta D ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b RTI INTERNATIONAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7ALPHA (4,8,12 TRIMETHYLTRIDECYL)ESTRA 1,3,5 TRIEN 3,17BETA DIOL; ALPHA TOCOPHEROL; ESTRADIOL; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FULVESTRANT; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ESTROGEN ACTIVITY; HIPPOCAMPUS; NERVE CELL; NEUROPROTECTION; NONHUMAN; RAT;

ANIMALS; BINDING, COMPETITIVE; CELL SURVIVAL; CELLS, CULTURED; COMPUTER SIMULATION; DRUG DESIGN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; ESTROGEN RECEPTOR MODULATORS; ESTROGENS; HIPPOCAMPUS; HUMANS; MODELS, MOLECULAR; NEURONS; NEUROPROTECTIVE AGENTS; RATS; STEREOISOMERISM; VITAMIN E;

EID: 34548507935     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070546x     Document Type: Article

References (57)

1. Fillit, H. M. The pharmacoeconomics of Alzheimer's disease. Am. J. Manage. Care 2000, 6, S1139-S1144.
2. Brookmeyer, R.; Gray, S.; Kawas, C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am. J. Public Health 1998, 88, 1337-1342.
3. Gao, S.; Hendrie, H. C.; Hall, K. S.; Hui, S. The relationship between age, sex, and the incidence of dementia and Alzheimer disease: A meta-analysis. Arch. Gen. Psychiatry 1998, 55, 809-815.
4. Zandi, P. P.; Carlson, M. C.; Plassman, B. L.; Welsh-Bohmer, K. A.; Mayer, L. S.; Steffens, D. C.; Breitner, J. C. Hormone replacement therapy and incidence of Alzheimer disease in older women: The Cache County Study. JAMA, J. Am. Med. Assoc. 2002, 288, 2123-2129.
5. Neurgaren, B. L.; Kraines, R. J. Menopausal symptoms in women of various ages. Psychosom. Med. 1965, 27, 266-273.
6. Sherwin, B. B., Impact of changing hormonal mileu on psychological functioning. In Treatment of the postmenopausal woman: Basic and clinical aspects. Lobo, R. A., Ed.; Lippincott Williams and Wilkins: Philadelphia, 1999; pp 179-188.
7. Brinton, R. D. A women's health issue: Alzheimer's disease and strategies for maintaining cognitive health. Int. J. Fertil. Women's Med. 1999, 44, 174-185.
8. Fillit, H. M.; O'Connell, A. W.; Refolo, L. M. Strategies for drug discovery for cognitive aging and Alzheimer's disease. J. Mol. Neurosci. 2002, 19, 1-3.
9. Henderson, V. W. Estrogen replacement therapy for the prevention and treatment of Alzheimer's disease. CNS Drugs 1997, 8, 343-351.
10. Zhao, L.; O'Neill, K.; Brinton, R. D. Selective estrogen receptor modulators (SERMs) for the brain: Current status and remaining challenges for developing NeuroSERMs. Brain Res. Rev. 2005, 49, 472-493.
11. Brinton, R. D. Estrogen therapy for prevention of Alzheimer's disease not for rehabilitation following onset of disease: the healthy cell bias of estrogen action. In Synaptic Plasticity: Basic Mechanisms to Clinical Applications. Baudry, M., Bi, R., Schreiber, S. S., Ed.; Taylor & Francis Group: New York, 2004; pp 131-157.
12. Chen, S.; Nilsen, J.; Brinton, R. D. Dose and temporal pattern of estrogen exposure determines neuroprotective outcome in hippocampal neuons: therapeutic implications. Endocrinology 2006, 147, 5303-5313.
13. Hammond, C. B. Women's concerns with hormone replacement therapy-compliance issues. Fertil. Steril. 1994, 62, 157S-160S.
14. Wassertheil-Smoller, S.; Hendrix, S. L.; Limacher, M.; Heiss, G.; Kooperberg, C.; Baird, A.; Kotchen, T.; Curb, J. D.; Black, H.; Rossouw, J. E.; Aragaki, A.; Safford, M.; Stein, E.; Laowattana, S.; Mysiw, W. J. Effect of estrogen plus progestin on stroke in postmenopausal women: The Women's Health Initiative: A randomized trial. JAMA, J. Am. Med. Assoc. 2003, 289, 2673-2684.
15. Manson, J. E.; Hsia, J.; Johnson, K. C.; Rossouw, J. E.; Assaf, A. R.; Lasser, N. L.; Trevisan, M.; Black, H. R.; Heckbert, S. R.; Detrano, R.; Strickland, O. L.; Wong, N. D.; Crouse, J. R.; Stein, E.; Cushman, M. Estrogen plus progestin and the risk of coronary heart disease. N. Engl. J. Med. 2003, 349, 523-534.
16. Zhao, L.; O'Neill, K.; Brinton, R. D. Estrogenic agonist activity of ICI 182,780 (Faslodex) in hippocampal neurons: implications for basic science understanding of estrogen signaling and development of estrogen modulators with a dual therapeutic profile. J. Pharmacol. Exp. Ther. 2006, 319, 1124-1132.
17. Wakeling, A. E.; Dukes, M.; Bowler, J. A potent specific pure antiestrogen with clinical potential. Cancer Res. 1991, 51, 3867-3873.
18. Pike, A. C.; Brzozowski, A. M.; Walton, J.; Hubbard, R. E.; Thorsell, A. G.; Li, Y. L.; Gustafsson, J. A.; Carlquist, M. Structural insights into the mode of action of a pure antiestrogen. Structure 2001, 9, 145-153.
19. Howell, A.; Osborne, C. K.; Morris, C.; Wakeling, A. E. ICI 182,780 (Faslodex): Development of a novel, "pure" antiestrogen. Cancer 2000, 89, 817-825.
20. Bross, P. F.; Cohen, M. H.; Williams, G. A.; Pazdur, R. FDA drug approval summaries: fulvestrant. Oncologist 2002, 7, 477-480.
21. Zhao, L.; Brinton, R. D. Structure-based virtual screening for plant-based ERβ-selective ligands as potential preventative therapy against age-related neurodegenerative diseases. J. Med. Chem. 2005, 48, 3463-3466.
22. Brzozowski, A. M.; Pike, A. C.; Dauter, Z.; Hubbard, R. E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G. L.; Gustafsson, J. A.; Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997, 389, 753-758.
23. Fawell, S. E.; Lees, J. A.; White, R.; Parker, M. G. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell 1990, 60, 953-962.
24. Navarro, A.; Gomez, C.; Sanchez-Pino, M. J.; Gonzalez, H.; Bandez, M. J.; Boveris, A. D.; Boveris, A. Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am. J. Physiol. 2005, 289, R1392-1399.
25. Lipinski, C. A.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 1997, 23, 3-25.
26. Abbott, N. J.; Ronnback, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 2006, 7, 41-53.
27. Habgood, M. D.; Begley, D. J.; Abbott, N. J. Determinants of passive drug entry into the central nervous system. Cell. Mol. Neurobiol. 2000, 20, 231-253.
28. Atkinson, F.; Cole, S.; Green, C.; van de Waterbeemd, H. Lipophilicity and other parameters affecting brain penetration. Curr. Med. Chem. 2002, 2, 229-240.
29. Iyer, M.; Mishru, R.; Han, Y.; Hopfinger, A. J. Predicting blood-brain barrier partitioning of organic molecules using membrane-interaction QSAR analysis. Pharm. Res. 2002, 19, 1611-1621.
30. Ma, X. L.; Chen, C.; Yang, J. Predictive model of blood-brain barrier penetration of organic compounds. Acta Pharmacol. Sin. 2005, 26, 500-512.
31. Loscher, W.; Potschka, H. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog. Neurobiol. 2005, 76, 22-76.
32. Misra, A.; Ganesh, S.; Shahiwala, A.; Shah, S. P. Drug delivery to the central nervous system: A review. J. Pharm. Sci. 2003, 6, 252-273.
33. Bowler, J.; Lilley, T. J.; Pittam, J. D.; Wakeling, A. E. Novel steroidal pure antiestrogens. Steroids 1989, 54, 71-99.
34. French, A. N.; Wilson, S. R.; Welch, M. J.; Katzenellenbogen, J. A. A synthesis of 7 alpha-substituted estradiols: Synthesis and biological evaluation of a 7 alpha-pentyl-substituted BODIPY fluorescent conjugate and a fluorine-18-labeled 7 alpha-pentylestradiol analog. Steroids 1993, 58, 157-169.
35. Tedesco, R.; Katzenellenbogen, J. A.; Napolitano, E. An expeditious route to 7a-substituted estradiol derivatives. Tetrahedron Lett. 1997, 38, 7997-8000.
36. Adamczyk, M.; Johnson, D. D.; Reddy, R. E. A stereoselective synthesis of 7 alpha-(3-carboxypropyl) estradiol from a noncontrolled substance. Steroids 1997, 62, 771-775.
37. Skaddan, M. B.; Wust, F. R.; Katzenellenbogen, J. A. Synthesis and binding affinities of novel recontaining 7α-substituted estradiol complexes: Models for breast cancer imaging agents. J. Org. Chem. 1999, 64, 8108-8121.
38. Hussey, S. L.; He, E.; Peterson, B. R. Synthesis of chimeric 7α-substituted estradiol derivatives linked to cholesterol and cholesterylamine. Org. Lett. 2002, 4, 415-418.
39. Blazejewski, J. C.; Wilmshurst, M. P.; Popkin, M. D.; Wakselman, C.; Laurent, G.; Nonclercq, D.; Cleeren, A.; Ma, Y.; Seo, H. S.; Leclercq, G. Synthesis, characterization and biological evaluation of 7α- perfluoroalkylestradiol derivatives. Bioorg. Med. Chem. 2003, 11, 335-345.
40. Jiang, X. R.; Sowell, J. W.; Zhu, B. T. Synthesis of 7α-substituted derivatives of 17β-estradiol. Steroids 2006, 71, 334-342.
41. Suga, T.; Ohta, S.; Nakai, A.; Munesada, K. Glycinoprenols: novel polyprenols possessing a phytyl residue from the leaves of soybean. J. Org. Chem. 1989, 54, 3390-3393.
42. 2. Bull. Chem. Soc. Jpn. 1983, 56, 2029-2032.
43. Akanni, A. O.; Marples, B. A. Improved preparation of 3,17β-diacetoxyestra-1,3,5(10)-trien-6-one. Syn. Commun. 1984, 14, 713-715.
44. Mitra, K.; Marquis, J. C.; Hillier, S. M.; Rye, P. T.; Zayas, B.; Lee, A. S.; Essigmann, J. M.; Croy, R. G. A rationally designed genotoxin that selectively destroys estrogen receptor-positive breast cancer cells. J. Am. Chem. Soc. 2002, 124, 1862-1863.
45. Kuiper, G. G.; Carlsson, B.; Grandien, K.; Enmark, E.; Haggblad, J.; Nilsson, S.; Gustafsson, J. A. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997, 138, 863-870.
46. Zhao, L.; Brinton, R. D. Select estrogens within the complex formulation of conjugated equine estrogens (Premarin) are protective against neurodegenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease. BMC Neurosci. 2006, 7, 24.
47. Wu, T.-W.; Wang, J. M.; Chen, S.; Brinton, R. D. 17β-Estradiol induced Ca2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expresion in rat hippocanpal neurons: A potential initiation mechanism for estrogen-induced neuroprotection. Neuroscience 2005, 135, 59-72.
48. 2+ rise and subsequent cyclic AMP response element-binding protein activation in hippocampal neurons: a potential initiation mechanism for estrogen neurotrophism. Neuroscience 2005, 132, 299-311.
49. Mannella, P.; Brinton, R. D. Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: A unified mechanism of estrogen action. J. Neurosci. 2006, 26, 9439-9447.
50. Singh, M. Ovarian hormones elicit phosphorylation of Akt and extracellular-signal regulated kinase in explants of the cerebral cortex. Endocr. J. 2001, 14, 407-415.
51. Znamensky, V.; Akama, K. T.; McEwen, B. S.; Milner, T. A. Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites. J. Neurosci. 2003, 23, 2340-2347.
52. Datta, S. R.; Dudek, H.; Tao, X.; Masters, S.; Fu, H.; Gotoh, Y.; Greenberg, M. E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997, 91, 231-241.
53. Nilsen, J.; Brinton, R. D. Mechanism of estrogen-mediated neuroprotection: regulation of mitochondial calcium and Bcl-2 expression. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 2842-2847.
54. Green, P. S.; Yang, S. H.; Simpkins, J. W. Neuroprotective effects of phenolic A ring oestrogens. Novartis Found. Symp. 2000, 230, 202-213.
55. Kellenberger, E.; Rodrigo, J.; Muller, P.; Rognan, D. Comparative evaluation of eight docking tools for docking and virtual screening accuracy. Proteins 2004, 57, 225-242.
56. Kontoyianni, M.; McClellan, L. M.; Sokol, G. S. Evaluation of docking performance: Comparative data on docking algorithms. J. Med. Chem. 2004, 47, 558-565.
57. Zhao, L.; Wu, T.-W.; Brinton, R. D. Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neurons. Brain Res. 2004, 1010, 22-34.