Abstract
The alteration in the biologic activity of the vitamin D3 molecule resulting from the replacement of a hydrogen atom with a fluorine atom is a subject of fundamental interest. To investigate this problem we synthesized 3β-fluorovitamin D3 and its hydrogen analog, 3-deoxyvitamin D3, and tested the biologic activity of each by in vitro and in vivo methods. Contrary to previous reports which showed that 3β-fluorovitamin D3 was as active as vitamin D3 in vivo, we found that the fluoro-analog was less active than vitamin D3. With regard to stimulation of intestinal calcium transport and bone calcium mobilization in the D-deficient hypocalcemic rat, 3β-fluorovitamin D3 showed significantly greater biologic activity than its hydrogen analog, 3-deoxyvitamin D3. In the organ-cultured, embryonic chick duodenum, 3β-fluorovitamin D3 was approx 1/1000th as active as the native hormone, 1,25-dihydroxyvitamin D3, while 3-deoxyvitamin D3 was inactive even at μM concentrations, in the induction of the vitamin D-dependent, calcium-binding protein. With regard to in vitro activity in displacing radiolabeled 25-hydroxyvitamin D3 from vitamin D binding protein and radiolabelled 1,25-dihydroxyvitamin D3 from a chick intestinal cytosol receptor, 3β-fluorovitamin D3 and 3β-deoxyvitamin D3 both showed very poor binding efficiencies when compared with vitamin D3. Our results show that the substitution of a fluorine atom for a hydrogen atom at the C-3 position of the vitamin D3 molecule results in a fluorovitamin with significantly more biological activity than its hydrogen analog, 3-deoxyvitamin D3.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 469-474 |
| Number of pages | 6 |
| Journal | Journal of Steroid Biochemistry |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1985 |
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ASJC Scopus subject areas
- Biochemistry
- Endocrinology
Cite this
Synthesis and biological activity of 3β-fluorovitamin D3 : Comparison of the biological activity of 3β-fluorovitamin D3 and 3-deoxyvitamin D3. / Murari, Martha Pass; Londowski, James M.; Bollman, Susan; Kumar, Rajiv.
In: Journal of Steroid Biochemistry, Vol. 22, No. 4, 1985, p. 469-474.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and biological activity of 3β-fluorovitamin D3
T2 - Comparison of the biological activity of 3β-fluorovitamin D3 and 3-deoxyvitamin D3
AU - Murari, Martha Pass
AU - Londowski, James M.
AU - Bollman, Susan
AU - Kumar, Rajiv
PY - 1985
Y1 - 1985
N2 - The alteration in the biologic activity of the vitamin D3 molecule resulting from the replacement of a hydrogen atom with a fluorine atom is a subject of fundamental interest. To investigate this problem we synthesized 3β-fluorovitamin D3 and its hydrogen analog, 3-deoxyvitamin D3, and tested the biologic activity of each by in vitro and in vivo methods. Contrary to previous reports which showed that 3β-fluorovitamin D3 was as active as vitamin D3 in vivo, we found that the fluoro-analog was less active than vitamin D3. With regard to stimulation of intestinal calcium transport and bone calcium mobilization in the D-deficient hypocalcemic rat, 3β-fluorovitamin D3 showed significantly greater biologic activity than its hydrogen analog, 3-deoxyvitamin D3. In the organ-cultured, embryonic chick duodenum, 3β-fluorovitamin D3 was approx 1/1000th as active as the native hormone, 1,25-dihydroxyvitamin D3, while 3-deoxyvitamin D3 was inactive even at μM concentrations, in the induction of the vitamin D-dependent, calcium-binding protein. With regard to in vitro activity in displacing radiolabeled 25-hydroxyvitamin D3 from vitamin D binding protein and radiolabelled 1,25-dihydroxyvitamin D3 from a chick intestinal cytosol receptor, 3β-fluorovitamin D3 and 3β-deoxyvitamin D3 both showed very poor binding efficiencies when compared with vitamin D3. Our results show that the substitution of a fluorine atom for a hydrogen atom at the C-3 position of the vitamin D3 molecule results in a fluorovitamin with significantly more biological activity than its hydrogen analog, 3-deoxyvitamin D3.
AB - The alteration in the biologic activity of the vitamin D3 molecule resulting from the replacement of a hydrogen atom with a fluorine atom is a subject of fundamental interest. To investigate this problem we synthesized 3β-fluorovitamin D3 and its hydrogen analog, 3-deoxyvitamin D3, and tested the biologic activity of each by in vitro and in vivo methods. Contrary to previous reports which showed that 3β-fluorovitamin D3 was as active as vitamin D3 in vivo, we found that the fluoro-analog was less active than vitamin D3. With regard to stimulation of intestinal calcium transport and bone calcium mobilization in the D-deficient hypocalcemic rat, 3β-fluorovitamin D3 showed significantly greater biologic activity than its hydrogen analog, 3-deoxyvitamin D3. In the organ-cultured, embryonic chick duodenum, 3β-fluorovitamin D3 was approx 1/1000th as active as the native hormone, 1,25-dihydroxyvitamin D3, while 3-deoxyvitamin D3 was inactive even at μM concentrations, in the induction of the vitamin D-dependent, calcium-binding protein. With regard to in vitro activity in displacing radiolabeled 25-hydroxyvitamin D3 from vitamin D binding protein and radiolabelled 1,25-dihydroxyvitamin D3 from a chick intestinal cytosol receptor, 3β-fluorovitamin D3 and 3β-deoxyvitamin D3 both showed very poor binding efficiencies when compared with vitamin D3. Our results show that the substitution of a fluorine atom for a hydrogen atom at the C-3 position of the vitamin D3 molecule results in a fluorovitamin with significantly more biological activity than its hydrogen analog, 3-deoxyvitamin D3.
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U2 - 10.1016/0022-4731(85)90162-1
DO - 10.1016/0022-4731(85)90162-1
M3 - Article
VL - 22
SP - 469
EP - 474
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - 4
ER -