Synthesis, conformational analysis, and biological evaluation of 19-nor-vitamin D3 analogues with A-ring modifications.
We have synthesized several isomers of 19-nor-vitamin D analogues possessing a hydroxy group at C-2 as well as novel derivatives bearing an epoxy substituent at the A-ring. All vitamins were prepared in convergent syntheses utilizing the modified Julia olefination. 1alpha,2alpha,25-Trihydroxy-19-nor-vitamin D(3) (3) and 2beta,3beta-epoxy-1alpha,25-dihydroxy-3-deoxy-19-nor-vitamin D(3) (10), which showed the highest affinity to the vitamin D receptor, displayed the highest potency among the tested compounds to inhibit the proliferation of MCF-7 breast cancer cells.
Sánchez-Abella
Laura
L
Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, Oviedo (Asturias), Spain.
Fernández
Susana
S
Verstuyf
Annemieke
A
Verlinden
Lieve
L
Gotor
Vicente
V
Ferrero
Miguel
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008968:Molecular Conformation; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018167:Receptors, Calcitriol; D002762:Cholecalciferol