Synthesis, characterization, and receptor interaction profiles of enantiomeric bile acids

Journal of Medicinal Chemistry

Volumn 50, Issue 24, 2007, Pages 6048-6058

  Katona, Bryson W ^a   Cummins, Carolyn L ^b   Ferguson, Andrew D ^b   Li, Tingting ^b   Schmidt, Daniel R ^b   Mangelsdorf, David J ^b   Covey, Douglas F ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; CELL NUCLEUS RECEPTOR; CHENODEOXYCHOLIC ACID; DETERGENT; FARNESOID X RECEPTOR; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR TGR5; LITHOCHOLIC ACID; PREGNANE X RECEPTOR; STEROID; TESTOSTERONE; UNCLASSIFIED DRUG; VITAMIN D RECEPTOR;

ANIMAL CELL; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; CRITICAL MICELLE CONCENTRATION; ENANTIOMER; ENANTIOSELECTIVITY; GENE CONTROL; HUMAN; HUMAN CELL; INFRARED SPECTROSCOPY; NONHUMAN; PROTEIN INTERACTION; PROTON NUCLEAR MAGNETIC RESONANCE; QUANTUM YIELD; RECEPTOR BINDING; RECEPTOR UPREGULATION; SYNTHESIS;

CELL LINE; CHENODEOXYCHOLIC ACID; DNA-BINDING PROTEINS; HUMANS; LITHOCHOLIC ACID; MICELLES; MODELS, MOLECULAR; RECEPTORS, CALCITRIOL; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, STEROID; STEREOISOMERISM; TRANSCRIPTION FACTORS;

EID: 37849022070     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0707931     Document Type: Article

References (41)

1. Pellicciari, R.; Costantino, G.; Fiorucci, S. Farnesoid X receptor: From structure to potential clinical applications. J. Med. Chem. 2005, 48, 5383-5403.
2. Makishima, M.; Okamoto, A. Y.; Repa, J. J.; Tu, H.; Learned, R. M.; Luk, A.; Hull, M. V.; Lustig, K. D.; Mangelsdorf, D. J.; Shan, B. Identification of a nuclear receptor for bile acids. Science (Washington, DC, U.S.) 1999, 284, 1362-1365.
3. Parks, D. J.; Blanchard, S. G.; Bledsoe, R. K.; Chandra, G.; Consler, T. G.; Kliewer, S. A.; Stimmel, J. B.; Willson, T. M.; Zavacki, A. M.; Moore, D. D.; Lehmann, J. M. Bile acids: Natural ligands for an orphan nuclear receptor. Science (Washington, DC, U.S.) 1999, 284, 1365-1368.
4. Wang, H. B.; Chen, J.; Hollister, K.; Sowers, L. C.; Forman, B. M. Endogenous bile acids are ligands for the nuclear receptor FXR BAR. Mol. Cell 1999, 3, 543-553.
5. Makishima, M. Nuclear receptors as targets for drug development: Regulation of cholesterol and bile acid metabolism by nuclear receptors. J. Pharmacol. Sci. 2005, 97, 177-183.
6. Staudinger, J. L.; Goodwin, B.; Jones, S. A.; Hawkins-Brown, D.; MacKenzie, K. I.; Latour, A.; Liu, Y. P.; Klaassen, C. D.; Brown, K. K.; Reinhard, J.; Willson, T. N.; Koller, B. H.; Kliewer, S. A. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 3369-3374.
7. Xie, W.; Radominska-Pandya, A.; Shi, Y. H.; Simon, C. M.; Nelson, M. C.; Ong, E. S.; Waxman, D. J.; Evans, R. M. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 3375-3380.
8. Makishima, M.; Lu, T. T.; Xie, W.; Whitfield, G. K.; Domoto, H.; Evans, R. M.; Haussler, M. R.; Mangelsdorf, D. J. Vitamin D receptor as an intestinal bile acid sensor. Science (Washington, DC, U.S.) 2002, 296, 1313-1316.
9. Kliewer, S. A.; Willson, T. M. Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor. J. Lipid Res. 2002, 43, 359-64.
10. Liu, Y. P.; Binz, J.; Numerick, M. J.; Dennis, S.; Luo, G. Z.; Desai, B.; MacKenzie, K. I.; Mansfield, T. A.; Kliewer, S. A.; Goodwin, B.; Jones, S. A. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J. Clin. Invest. 2003, 112, 1678-1687.
11. Szapary, P. O.; Wolfe, M. L.; Bloedon, L. T.; Cucchiara, A. J.; DerMarderosian, A. H.; Cirigliano, M. D. Guggulipid for the treatment of hypercholesterolemia - A randomized controlled trial. J. Am. Med. Assoc. 2003, 290, 765-772.
12. Owsley, E.; Chiang, J. Y. Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7α-hydroxylase gene. Biochem. Biophys. Res. Commun. 2003, 304, 191-195.
13. Zollner, G.; Marschall, H. U.; Wagner, M.; Trauner, M. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: Pathogenetic and therapeutic considerations. Mol. Pharmacol. 2006, 3, 231-251.
14. Yee, Y. K.; Chintalacharuvu, S. R.; Lu, J.; Nagpal, S. Vitamin D receptor modulators for inflammation and cancer. Mini Rev. Med. Chem. 2005, 5, 761-778.
15. Gombart, A. F.; Luong, Q. T.; Koeffler, H. P. Vitamin D compounds: Activity against microbes and cancer. Anticancer Res. 2006, 26, 2531-2542.
16. Kawamata, Y.; Fujii, R.; Hosoya, M.; Harada, M.; Yoshida, H.; Miwa, M.; Fukusumi, S.; Habata, Y.; Itoh, T.; Shintani, Y.; Hinuma, S.; Fujisawa, Y.; Fujino, M. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 2003, 278, 9435-9440.
17. Maruyama, T.; Miyamoto, Y.; Nakamura, T.; Tamai, Y.; Okada, H.; Sugiyama, E.; Nakamura, T.; Itadani, H.; Tanaka, K. Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun. 2002, 298, 714-719.
18. Watanabe, M.; Houten, S. M.; Mataki, C.; Christoffolete, M. A.; Kim, B. W.; Sato, H.; Messaddeq, N.; Harney, J. W.; Ezaki, O.; Kodama, T.; Schoonjans, K.; Bianco, A. C.; Auwerx, J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature (London, U.K.) 2006, 439, 484-489.
19. Michéli, R. A.; Hajos, Z. G.; Cohen, N.; Parrish, D. R.; Portland, L. A.; Sciamanna, W.; Scott, M. A.; Wehrli, P. A. Total syntheses of optically active 19-norsteroids. (+)-Estr-4-ene-3,17-dione and (+)-13β-ethylgon-4- ene-3,17-dione. J. Org. Chem. 1975, 40, 675-681.
20. Rychnovsky, S. D.; Mickus, D. E. Synthesis of ent-cholesterol, the unnatural enantiomer. J. Org. Chem. 1992, 57, 2732-2736.
21. Katona, B. W.; Krishnan, K.; Cai, Z. Y.; Manion, B. D.; Benz, A.; Taylor, A.; Evers, A. S.; Zorumski, C. F.; Mennerick, S.; Covey, D. F. Neurosteroid analogues. 12. Potent enhancement of GABA-mediated chloride currents at GABAA receptors by ent-androgens. Eur. J. Med. Chem., in press.
22. Han, M. C.; Zorumski, C. F.; Covey, D. F. Neurosteroid analogues. 4. The effect of methyl substitution at the C-5 and C-10 positions of neurosteroids on electrophysiological activity at GABA(A) receptors. J. Med. Chem. 1996, 39, 4218-4232.
23. Templeton, J. F.; Kumar, V. P. S. Synthesis of ring-A and -B substituted 17α-acetoxypregnan-20-one derivatives with potential activity on the digitalis receptor in cardiac muscle. J. Chem. Soc., Perkin Trans. I 1987, 1361-1368.
24. Westover, E. J.; Covey, D. F. First synthesis of ent-desmosterol and its conversion to ent-deuterocholesterol. Steroids 2003, 68, 159-166.
25. Tochtrop, G. P.; DeKoster, G. T.; Cistola, D. P.; Covey, D. F. Synthesis of [3,4-C-13(2)]-enriched bile salts as NMR probes of protein-ligand interactions. J. Org. Chem. 2002, 67, 6764-6771.
26. Lai, C. K.; Byon, C. Y.; Gut, M. Synthesis of 3α,7α- dihydroxy-5β-androstan-17-one. Steroids 1983, 42, 707-711.
27. Wovkulich, P. M.; Batcho, A. D.; Uskokoviæ, M. R. Stereoselective introduction of steroid side chains. Synthesis of chenodeoxycholic acid. Helv. Chim. Acta 1984, 67, 612-615.
28. Roda, A.; Hofmann, A. F.; Mysels, K. J. The influence of bile salt structure on self-association in aqueous solutions. J. Biol. Chem. 1983, 258, 6362-6370.
29. Nair, P. P.; Kritchevsky, D. The Bile Acids: Chemistry, Physiology, and Metabolism; Plenum Press: New York, 1971; Vol. 1.
30. Carnahan, V. E.; Redinbo, M. R. Structure and function of the human nuclear xenobiotic receptor PXR. Curr. Drug Metab. 2005, 6, 357-367.
31. Yu, J.; Lo, J. L.; Huang, L.; Zhao, A.; Metzger, E.; Adams, A.; Meinke, P. T.; Wright, S. D.; Cui, J. Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J. Biol. Chem. 2002, 277, 31441-31447.
32. Maloney, P. R.; Parks, D. J.; Haffner, C. D.; Fivush, A. M.; Chandra, G.; Plunket, K. D.; Creech, K. L.; Moore, L. B.; Wilson, J. G.; Lewis, M. C.; Jones, S. A.; Willson, T. M. Identification of a chemical tool for the orphan nuclear receptor FXR. J. Med. Chem. 2000, 43, 2971-2974.
33. Mi, L. Z.; Devarakonda, S.; Harp, J. M.; Han, Q.; Pellicciari, R.; Willson, T. M.; Khorasanizadeh, S.; Rastinejad, F. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol. Cell 2003, 11, 1093-1100.
34. Houten, S. M.; Watanabe, M.; Auwerx, J. Endocrine functions of bile acids. EMBO J. 2006, 25, 1419-1425.
35. Biellmann, J. F. Enantiomeric steroids: Synthesis, physical, and biological properties. Chem. Rev. 2003, 103, 2019-2033.
36. Westover, E. J.; Covey, D. F.; Brockman, H. L.; Brown, R. E.; Pike, L. J. Cholesterol depletion results in site-specific increases in epidermal growth factor receptor phosphorylation due to membrane level effects - Studies with cholesterol enantiomers. J. Biol. Chem. 2003, 278, 51125-51133.
37. Alakoskela, J. M.; Covey, D. F.; Kinnunen, P. K. J. Lack of enantiomeric specificity in the effects of anesthetic steroids on lipid bilayers. Biochim. Biophys. Acta 2007, 1768, 131-145.
38. O'Neil, M. J. The Merck Index, 14th ed.; Merck Research Laboratories: Whitehouse Station, NJ, 2006.
39. Kametani, T. Studies on the syntheses of heterocyclic and natural compounds. 950. Asymmetric total synthesis of (+)-chenodeoxycholic acid. Stereoselectivity of intramolecular cycloaddition of olefinic o-quinodimethanes. J. Org. Chem. 1982, 47, 2331-2342.
40. Yu, J. H.; Lo, J. L.; Huang, L.; Zhao, A.; Metzger, E.; Adam, A.; Meinke, P. T.; Wright, S. D.; Cui, J. S. Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J. Biol. Chem. 2002, 277, 31441-31447.
41. Bookout, A. L.; Cummins, C. L.; Mangelsdorf, D. J. High-throughput real-time quantitative reverse transcription PCR. Curr. Protocols Mol. Biol. 2005, 15.8.1-15.8.21.