The first locked side-chain analogues of calcitriol (1alpha,25-dihydroxyvitamin D3) induce vitamin D receptor transcriptional activity.
[structure: see text]. We describe the synthesis of the first locked side-chain analogues of the natural hormone 1alpha,25-(OH)2-D3 and their effects on gene transcription in human colon cancer cells. Analogue 2 was more potent than 1alpha,25-(OH)2-D3 at inducing vitamin D receptor (VDR) transcriptional activity. Analogues 3a and 3b show potency similar to that of 1alpha,25-(OH)2-D3, whereas 3c was less active. The novel analogues efficiently bind VDR in vivo to induce transcription from a consensus vitamin D responsive element (VDRE).
Pérez-García
Xenxo
X
Departamento de Química Orgánica y Unidad Asociada al CSIC, Universidad de Santiago de Compostela, 15706 Santiago de Compostela, Madrid, Spain.
Rumbo
Antonio
A
Larriba
María Jesús
MJ
Ordóñez
Paloma
P
Muñoz
Alberto
A
Mouriño
Antonio
A
D000480:Alkynes / Q000737:chemistry; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D015394:Molecular Structure; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000502:physiology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*; D030181:Vitamin D Response Element / Q000235:genetics
D000480:Alkynes; D006841:Hydrocarbons, Aromatic; D018167:Receptors, Calcitriol; D008156:Luciferases; D002117:Calcitriol