17alpha;-Hydroxy-25-fluorovitamin D3: a potent analog of 1α,25-dihydroxyvitamin D3

Publisher Website
Google Scholar
Abstract
Chemically synthesized 1.alpha.-hydroxy-25-fluorovitamin D3 was compared to 1,25-dihydroxyvitamin D3 for potency in the chick intestinal cytosol-binding protein assay, induction of intestinal Ca transport, mobilization of Ca from bone and epiphyseal plate calcification in the rat. The 25-fluorinated analogue causes 50% displacement of 1,25-dihydroxy[23,24-3H]D3 at 1.8 .times. 10-8 M in the competitive protein-binding assay; only 5.6 .times. 10-11 M of unlabeled 1,25-dihydroxyvitamin D3 is needed for equal competition. This 315-fold difference between the activities of 1,25-dihydroxyvitamin D3 and 1.alpha.-hydroxy-25-fluorovitamin D3 indicates that the fluoro analogue is about equipotent with 1.alpha.-hydroxyvitamin D3 in the protein-binding assay. However, 1.alpha.-hydroxy-25-fluorovitamin D3 is 1/50 as active as 1,25-dihydroxyvitamin D3 in vivo in the stimulation of intestinal Ca transport and bone Ca mobilization in vitamin D deficient rats on a low Ca diet. Likewise, 1.alpha.-hydroxy-25-fluorovitamin D3 is about 40 times less active than 1,25-dihydroxyvitamin D3 in inducing endochondrial calcification in rachitic rats. No selective actions of 1.alpha.-hydroxy-25-fluorovitamin D3 were noted. Since the 25 position of the analogue is blocked by a F atom, it appears that 25-hydroxylation of 1.alpha.-hydroxylated vitamin D compounds in vivo is not an obligatory requirement for appreciable vitamin D activity.