K. Allewaert et al., THE BIOLOGICAL-ACTIVITY OF 23-OXA-DIHYDROXYVITAMIN-D-3, 23-OXA-24-OXO-DIHYDROXYVITAMIN-D-3, AND 23-THIA-DIHYDROXYVITAMIN-D-3, Steroids, 59(12), 1994, pp. 686-690
Three analogs of 1 alpha,25-(OH)(2)D-3 with an oxygen ol another heter
oatom at position 23 were synthesized in search of separating the cell
-differentiating from the calcemic effects of the vitamin D hormone. T
heir ability to induce superoxide production in human myeloid leukemia
cells (HL-60) was 1 alpha,25-(OH)(2)D-3 > 23-oxa-24-oxo-1 alpha,25-(O
H)(2)D-3 > 23-thia-1 alpha,25-(OH)(2)D-3 > 23-oxa-1 alpha,25-(OH)(2)D-
3. 23-oxa-24-oxo-1 alpha,25(OH)(2)D-3 was slightly more potent than 1
alpha,25-(OH)(2)D-3 in inhibiting cell proliferation in MCF-7 cells an
d 23-thia- and 23-oxa-1 alpha,25(OH)(2)D-3 were less potent. Their in
vitro potency to produce osteocalcin in MG-63 cells was 1 alpha,25-(OH
)(2)D-3 > 23-oxa-24-oxo-1 alpha,25-(OH)(2)D-3 > 23-thia-1 alpha,25-(OH
)(2)D-3 = 23-oxa-1 alpha,25-(OH)(2)D-3. All three analogs had reduced
receptor and DBP affinity compared to 1 alpha,25-(OH)(2)D-3. When thes
e analogs were injected in rachitic chicks, only little calcemic effec
ts were observed. The introduction of a heteroatom in carbon 23 of 1 a
lpha,25-(OH)(2)D-3 thus creates analogs with dissociated action on cel
l differentiation and calcium homeostasis.