Synthesis and biological activity of 3β-fluorovitamin D3: Comparison of the biological activity of 3β -fluorovitamin D3 and 3-deoxyvitamin D3

Larry K. Revelle, James M. Londowski, Susan Bollman Kost, Robert A. Corradino, Rajiv Kumar

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)469-474
Number of pages6
JournalJournal of Steroid Biochemistry
Volume22
Issue number4
DOIs
StatePublished - 1985

Fingerprint

Cholecalciferol
Bioactivity
Hydrogen
Atoms
Fluorine
Calcitriol
S100 Calcium Binding Protein G
Vitamin D-Binding Protein
Calcium
Calcifediol
Molecules
Duodenum
Cytosol
Rats
Bone
Substitution reactions
3-deoxyvitamin D3
Hormones
Bone and Bones
In Vitro Techniques

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. / Revelle, Larry K.; Londowski, James M.; Kost, Susan Bollman; Corradino, Robert A.; Kumar, Rajiv.

In: Journal of Steroid Biochemistry, Vol. 22, No. 4, 1985, p. 469-474.

Research output: Contribution to journalArticle

Revelle, Larry K. ; Londowski, James M. ; Kost, Susan Bollman ; Corradino, Robert A. ; Kumar, Rajiv. / Synthesis and biological activity of 3β-fluorovitamin D3 : Comparison of the biological activity of 3β -fluorovitamin D3 and 3-deoxyvitamin D3. In: Journal of Steroid Biochemistry. 1985 ; Vol. 22, No. 4. pp. 469-474.
@article{17134c3903034f5d843cd5eceab454eb,
title = "Synthesis and biological activity of 3β-fluorovitamin D3: Comparison of the biological activity of 3β -fluorovitamin D3 and 3-deoxyvitamin D3",
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 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.",
author = "Revelle, {Larry K.} and Londowski, {James M.} and Kost, {Susan Bollman} and Corradino, {Robert A.} and Rajiv Kumar",
year = "1985",
doi = "10.1016/0022-4731(85)90164-5",
language = "English (US)",
volume = "22",
pages = "469--474",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",
number = "4",

}

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

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 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.

UR - http://www.scopus.com/inward/record.url?scp=0021864014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021864014&partnerID=8YFLogxK

U2 - 10.1016/0022-4731(85)90164-5

DO - 10.1016/0022-4731(85)90164-5

M3 - Article

AN - SCOPUS:0021864014

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 -