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 - Revelle, Larry K.
AU - Londowski, James M.
AU - Kost, Susan Bollman
AU - Corradino, Robert A.
AU - Kumar, Rajiv
N1 - Funding Information:
*To whom corresoondence should be addressed. Supported by NIH Grand AM 25409. iDepartment of Physiology, Cornell University, Ithaca, New York, U.S.A. ‘Abbreviation: 3/3-Fluoro-vitamin D,, 9, IO-seco-5,7,10(19)-cholestadiene. 2Abbreviation: 3-Deoxyvitamin D,, 9, IO-seco-5,7,10(19)-cholestadiene.
PY - 1985/4
Y1 - 1985/4
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 6 and its hydrogen analog, 3-deoxyvitarnin D3 7, 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 snowed 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 μ M 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 6 with significantly more biological activity than its hydrogen analog, 3-deoxyvitamin D3 7.
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 6 and its hydrogen analog, 3-deoxyvitarnin D3 7, 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 snowed 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 μ M 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 6 with significantly more biological activity than its hydrogen analog, 3-deoxyvitamin D3 7.
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U2 - 10.1016/0022-4731(85)90164-5
DO - 10.1016/0022-4731(85)90164-5
M3 - Article
C2 - 2987615
AN - SCOPUS:0021864014
SN - 0022-4731
VL - 22
SP - 469
EP - 474
JO - Journal of Steroid Biochemistry
JF - Journal of Steroid Biochemistry
IS - 4
ER -