Synthesis and biological evaluation of new 6-s-cis locked 1,2,25-trihydroxyprevitamin D3 analogues.
An efficient synthesis of several diastereomers of 2-hydroxy substituted 1alpha,25-dihydroxyprevitamin D3 derivatives was accomplished utilizing a practical route to the A-ring synthon. The biological activity of the analogues was evaluated in vitro. All the synthesized derivatives demonstrated low affinity for the vitamin D receptor and vitamin D-binding protein compared with 1alpha,25-dihydroxyvitamin D3, the natural hormone. 1alpha,2beta,25-trihydroxy-19-nor-pre-D3 was the most potent of the analogues in inhibiting proliferation of MCF-7 cells but requires higher EC50 concentrations than 1alpha,25-dihydroxyvitamin D3.
Sánchez-Abella
Laura
L
Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, 33006 Oviedo (Asturias), Spain.
Fernández
Susana
S
Verstuyf
Annemieke
A
Verlinden
Lieve
L
Ferrero
Miguel
M
Gotor
Vicente
V
D002460:Cell Line; D049109:Cell Proliferation; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
D002762:Cholecalciferol