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 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Fingerprint Dive into the research topics of 'Synthesis and biological activity of 3β-fluorovitamin D<sub>3</sub>: Comparison of the biological activity of 3β -fluorovitamin D<sub>3</sub> and 3-deoxyvitamin D<sub>3</sub>'. Together they form a unique fingerprint.

  • Cite this