Artículo
Del Fueyo, M.C.; Dansey, M.V.; Paolo, L.S.; Pecci, A.; Veleiro, A.S.; Burton, G. "C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands" (2016) Steroids. 112:109-114
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Abstract:
The DAF-12 receptor in nematodes and the Liver X Receptor (LXR) in mammals are structurally related transcription factors that play key roles in determining the life span of the organism. Both types of receptors are activated by oxysterols, cholesterol metabolites with oxidized side chains. Restricting the movement of the oxysterol side chain to certain orientations may have profound effects in the activity profile, however this has not been explored so far. In a first attempt to obtain analogues of natural ligands of DAF-12 and LXR with restricted side chain mobility we introduced a 16,22-oxygen bridge in 26-hydroxycholesterol, a cholestenoic acid and a dafachronic acid (5-7). Diosgenin was used as starting material, the key step to obtain the 16,22 epoxy functionality was the one pot formation and reduction of a cyclic hemiketal via the oxocarbenium ion using sodium cyanoborohydride. All new compounds were characterized by NMR and mass spectrometry and assayed as ceDAF-12 or LXR ligands in transactivation cell-based assays. The dafachronic acid analogue 7 behaved as a ceDAF-12 agonist. © 2016 Elsevier Inc. All rights reserved.
Registro:
| Documento: | Artículo |
| Título: | C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands |
| Autor: | Del Fueyo, M.C.; Dansey, M.V.; Paolo, L.S.; Pecci, A.; Veleiro, A.S.; Burton, G. |
| Filiación: | Departamento de Química Orgánica, UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Ciudad de Buenos Aires, C1428EGA, Argentina Departamento de Química Biológica, IFIBYNE (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Ciudad de Buenos Aires, C1428EGA, Argentina |
| Palabras clave: | DAF-12 receptor; Dafachronic acid; Liver X Receptor; Oxocarbenium reduction; Oxysterols; 26 hydroxycholesterol; bacterial protein; cell nucleus receptor; DAF 12 receptor; DAF 12 receptor agonist; diosgenin; hormone receptor stimulating agent; liver X receptor; liver X receptor agonist; unclassified drug; cholestane derivative; cholesterol derivative; dafachronic acid; liver X receptor; oxysterol; animal cell; Article; controlled study; desilylation; DNA binding; heteronuclear single quantum coherence; human; human cell; isomerization; ligand binding; mass spectrometry; nonhuman; nuclear magnetic resonance; oxidation; promoter region; protein conformation; reporter gene; stereochemistry; stereoisomerism; transactivation; transactivation assay; agonists; animal; cell line; chemical structure; chemistry; hamster; HEK293 cell line; metabolism; nuclear magnetic resonance spectroscopy; Animals; Cell Line; Cholestenes; Cricetinae; HEK293 Cells; Humans; Hydroxycholesterols; Liver X Receptors; Magnetic Resonance Spectroscopy; Molecular Structure; Oxysterols |
| Año: | 2016 |
| Volumen: | 112 |
| Página de inicio: | 109 |
| Página de fin: | 114 |
| DOI: | http://dx.doi.org/10.1016/j.steroids.2016.05.009 |
| Título revista: | Steroids |
| Título revista abreviado: | Steroids |
| ISSN: | 0039128X |
| CODEN: | STEDA |
| CAS: | 26 hydroxycholesterol, 13095-61-9; diosgenin, 512-04-9; Cholestenes; dafachronic acid; Hydroxycholesterols; Liver X Receptors; Oxysterols |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v112_n_p109_DelFueyo |
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Citas:
---------- APA ----------
Del Fueyo, M.C., Dansey, M.V., Paolo, L.S., Pecci, A., Veleiro, A.S. & Burton, G. (2016) . C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands. Steroids, 112, 109-114.http://dx.doi.org/10.1016/j.steroids.2016.05.009
---------- CHICAGO ----------
Del Fueyo, M.C., Dansey, M.V., Paolo, L.S., Pecci, A., Veleiro, A.S., Burton, G. "C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands" . Steroids 112 (2016) : 109-114.http://dx.doi.org/10.1016/j.steroids.2016.05.009
---------- MLA ----------
Del Fueyo, M.C., Dansey, M.V., Paolo, L.S., Pecci, A., Veleiro, A.S., Burton, G. "C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands" . Steroids, vol. 112, 2016, pp. 109-114.http://dx.doi.org/10.1016/j.steroids.2016.05.009
---------- VANCOUVER ----------
Del Fueyo, M.C., Dansey, M.V., Paolo, L.S., Pecci, A., Veleiro, A.S., Burton, G. C(16)-C(22) oxygen-bridged analogues of ceDAF-12 and LXR ligands. Steroids. 2016;112:109-114.http://dx.doi.org/10.1016/j.steroids.2016.05.009
