1 alpha-hydroxy-25-fluorovitamin D3: a potent analogue of 1 alpha,25-dihydroxyvitamin D3.
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 calcium transport, mobilization of calcium 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 X 10(-8) M in the competitive protein-binding assay, whereas only 5.6 X 10(-11) M of unlabeled 1,25-dihydroxyvitamin D3 is needed for equal competition. This 315-fold difference between 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 calcium transport and bone calcium mobilization in vitamin D deficient rats on a low-calcium 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 1alpha-hydroxy-25-fluorovitamin D3 were noted. Since the 25 position of the analogue is blocked by a fluorine 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.
D000818:Animals; D001667:Binding, Competitive; D001842:Bone and Bones / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002645:Chickens; D006887:Hydroxycholecalciferols / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
D006887:Hydroxycholecalciferols; C017403:1-hydroxy-25-fluorovitamin D3; D002118:Calcium