Diastereotopic and deuterium effects in gemini

Journal of Medicinal Chemistry

Volumn 56, Issue 10, 2013, Pages 3878-3888

  Maehr, Hubert ^a   Rochel, Natacha ^b   Lee, Hong Jin ^a,d   Suh, Nanjoo ^a,c   Uskokovic, Milan R ^a  

^a RUTGERS UNIVERSITY   (United States)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^d Chung Ang University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

1ALPHA, 25 DIHYDROXYVITAMIN D3; DEUTERIUM; DIHYDROXYCOLECALCIFEROL; METHYL GROUP; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; BREAST CANCER; CANCER CELL; CANCER INHIBITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DIASTEREOISOMER; DISTORTION PRODUCT OTOACOUSTIC EMISSION; HUMAN; HUMAN CELL; ZEBRA FISH;

ANIMALS; ANTINEOPLASTIC AGENTS; CALCITRIOL; CELL LINE, TUMOR; CHROMATOGRAPHY, THIN LAYER; CRYSTALLOGRAPHY, X-RAY; DEUTERIUM; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; INDICATORS AND REAGENTS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; RECEPTORS, CALCITRIOL; SPECTROPHOTOMETRY, ULTRAVIOLET; STEREOISOMERISM; ZEBRAFISH;

EID: 84878075977     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400032t     Document Type: Article

References (42)

1. Foster, A. B. Deuterium isotope effects in the metabolism of drugs and xenobiotics: implications for drug design Adv. Drug Res. 1985, 1, 2
2. Mutlib, A. E. Application of stable labeled compounds in metabolism and in metabolism-mediated toxicity studies Chem. Res. Toxicol. 2008, 1672-1689
3. Kushner, D. J.; Baker, A.; Dunstall, T. G. Pharmacological uses and perspectives of heavy water and deuterated compounds Can. J. Physiol. Pharmacol. 1999, 77, 79-88
4. Carlberg, C. Molecular basis of the selective activity of vitamin D analogues J. Cell. Biochem. 2003, 88, 274-281
5. 3 receptor J. Biol. Chem. 1999, 274, 16836-16845
6. 3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system Genes Dev. 1998, 12, 1787-1800
7. 3 with two side chains: interaction with its nuclear receptor and cellular action J. Med. Chem. 2000, 43, 2719-2730
8. Uskokovic, M. R; Maehr, H.; Reddy, S. G; Li, Y. C.; Adorini, L.; Holick, M. F. Gemini: the 1,25-dihydroxy vitamin D analogs with two side-chains. Vitamin D, 2nd ed.; Feldman, D.; Pike, J. W.; Glorieux, F. H., Eds.; Elsevier Academic Press: London, 2005; pp 1511-1524.
9. Lee, H. J.; Ji, Y.; Paul, S.; Maehr, H.; Uskokovic, M.; Suh, N. Activation of bone morphogenetic protein signaling by a gemini vitamin D3 analogue is mediated by Ras/protein kinase Cα Cancer Res. 2007, 67, 11840-11847
10. Lee, H. J.; Paul, S.; Atalla, N.; Thomas, P. E.; Lin, X.; Yang, I.; Buckley, B.; Lu, G.; Zheng, X.; Lou, Y. R.; Conney, A. H.; Maehr, H.; Adorini, L.; Uskokovic, M.; Suh, N. Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity Cancer Prev. Res. 2008, 1960, 1-9
11. So, J. Y.; Lee, H. J.; Smolarek, A. K.; Paul, S.; Wang, C.-X.; Maehr, H.; Uskokovic, M.; Zheng, X.; Conney, A.; Cai, L.; Liu, F.; Suh, N. A novel vitamin D analog represses the expression of stem cell marker CD44 in breast cancer Mol. Pharmacol. 2011, 79, 360-367
12. Burch, W. M.; Lopez-Claros, M.; Uskokovic, M. R.; Drezner, M. K. 1,25-Dihydroxyvitamin D3 stimulates avian and mammalian cartilage growth in vitro J. Bone Mineral Res. 1988, 3, 87-91
13. Sanderson, K. Big interest in heavy drugs Nature 2009, 458, 269
14. Maehr, H.; Uskokovic, M. R.; Adorini, L.; Penna, G.; Mariani, R.; Panina, P.; Passini, N.; Bono, E.; Perego, S.; Biffi, M.; Holick, M.; Spina, C.; Suh, N. Calcitriol derivatives with two different side chains at C-20. III. An epimeric pair of the gemini family with unprecedented antiproliferative effects on tumor cells and renin mRNA expression inhibition J. Steroid Biochem. Mol. Biol. 2007, 103, 277-281
15. Maehr, H.; Lee, H. J.; Perry, B.; Suh, N.; Uskokovic, M. R. Calcitriol derivatives with two different side chains at C20. V. Potent inhibitors of mammary carcinogenesis and inducers of leukemia differentiation J. Med. Chem. 2009, 52, 5505-5519
16. Spina, C.; Tangpricha, V.; Min, Y.; Zhou, W.; Wolfe, M.; Maehr, H.; Uskokovic, M.; Adorini, L.; Holick, M. F. Colon cancer and ultraviolet B radiation and prevention and treatment of colon cancer in mice with vitamin D and its gemini analogs J. Steroid Biochem. Mol. Biol. 2005, 97, 111-120
17. 3 through C-24 oxidation pathway Biochemistry 1989, 28, 1763-1769
18. 3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation Biochem. J. 1989, 262, 173-180
19. Maehr, H.; Uskokovic, M. R.; Adorini, L.; Reddy, S. D. Calcitriol derivatives with two different side chains at C-20. II. Diastereoselective syntheses of the metabolically produced 24(R) hydroxygemini J. Med. Chem. 2004, 47, 6478-6484
20. 3-26,23-lactone J. Biol. Chem. 1984, 259, 884-889
21. 3-26,23-lactone biosynthesis Biochemistry 1984, 23, 3973-3976
22. Bouillon, R. O., W. H.; Norman, A. W. Structure-function relationships in the vitamin D endocrine system Endocr. Rev. 1995, 16, 200-257
23. 3: unique hydroxylated metaboles formed during catalysis with cytochrome P450scc (CYP11A1) Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 13754-14759
24. Binderup, L.; Latini, S.; Binderup, E.; Bertting, C.; Calverley, M.; Hansen, K. 20-Epivitamin D3 analogues: a novel class of potent regulators of cell growth and immune responses Biochem. Pharmacol. 1991, 42, 1569-1575
25. Dilworth, F. J.; Calverly, M. J.; Makin, H.; Jones, G. Increased biological activity of 20-epi-1,25-dihydroxyvitamin D3 is due to reduced catabolism and altered protein binding Biochem. Pharmacol. 1994, 47, 987-993
26. 3 analogs (MC 1288, KH 1060, EB 1089, GS 1558, and CB 1093): studies on their mechanism of action Steroids 2001, 66, 223-225
27. Rochel, N.; Wurtz, J. M.; Mitschler, A.; Klaholz, B.; Moras, D. The crystal structure of the nuclear receptor for vitamin D, bound to its natural ligand Mol. Cell 2000, 5, 173-9
28. Ciesielski, F.; Rochel, N.; Mitschler, A.; Kouzmenko, A.; Moras, D. Structural investigation of the ligand binding domain of the zebrafish VDR in complex with 1a25(OH2D3 and gemini: purification, crystallization and preliminary X-ray diffraction analysis J. Steroid Biochem. Mol. Biol. 2004, 89-90, 55-59
29. Ciesielski, F.; Rochel, N.; Moras, D. Adaptability of the vitamin D nuclear receptor to the synthetic ligand gemini: Remodeling the LPB with one side chain rotation J. Steroid Biochem. Mol. Biol. 2007, 103, 235-242
30. Rochel, N.; Moras, D. Ligand binding domain of vitamin D receptors Curr. Top. Med. Chem. 2006, 6, 1229-41
31. Rochel, N.; Moras, D. Vitamin D Nuclear Receptor Ligand-Binding Domain Crystal Structure. In Vitamin D, 2nd ed.; Feldman, D.; Pike, J. W; Glorieux, F. H., Eds.; Elsevier Academic Press: Burlington, MA, 2005; pp 279-289.
32. Huet, T.; Maehr, H.; Lee, H. J.; Uskokovic, M. R.; Suh, N.; Moras, D.; Rochel, N. Structure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097 Med. Chem. Commun. 2011, 2, 424-429
33. 3 analogs with bis C-20 side chains as therapeutic agents. Patent WO9849138, 1998, 35 pp.
34. Manchand, P. S.; Uskokovic, M. R. Method of using vitamin D analogs with bis C-20 side chains for treating or preventing neoplastic diseases. U.S. Patent US 6008209, 1999, 13 pp.
35. Maehr, H.; Uskokovic, M. R. Formal desymmetrization of the diastereotopic chains in gemini calcitriol derivatives with two different side chains at C-20 Eur. J. Org. Chem. 2004, 1703-1713
36. Manchand, P. S.; Yiannikouros, G. P.; Belica, P. S.; Madan, P. Nickel-mediated conjugate addition. Elaboration of calcitriol from ergocalciferol J. Org. Chem. 1995, 60, 6574-6581
37. Pilcher, A. S; DeShong, P. Improved protocols for the selective deprotection of trialkylsilyl ethers using fluorosilicic acid J. Org. Chem. 1993, 58, 5130-5134
38. Baggiolin, E. G; Iacobelli, J. A.; Hennessy, B. M.; Batcho, A. D.; Sereno, J. F.; Uskokovic, M. R. Stereocontrolled total synthesis of 1.alpha.,25-dihydroxycholecalciferol and 1.alpha.,25-dihydroxyergocalciferol J. Org. Chem. 1986, 51, 3098-3108
39. 3 and analogues J. Org. Chem. 2002, 67, 1580-1587
40. Courtney, L. F.; Lange, M.; Uskokovic, M. R.; Wovkulich, P. M. Asymmetric synthesis of a key ring A synthon for 1α-hydroxy-19-nor vitamin D Tetrahedron Lett. 1998, 39, 3363-3366
41. Zuh, G.-D.; Okamura, W. H. Synthesis of vitamin D (calciferol) Chem. Rev. 1995, 95, 1877-1952
42. Wade, D. Deuterium isotope effects on noncovalent interactions between molecules Chem.-Biol. Interact. 1999, 117, 191-217