Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity

Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi Kittaka

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

2β-Substituted analogs of 14-epi-previtamin D3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46nM, respectively.

Original languageEnglish
Pages (from-to)20-24
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume121
Issue number1-2
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

Fingerprint

phosphine
Transcriptional Activation
Cholecalciferol
Epoxy Compounds
Osteocalcin
Testing
Isomerization
Oxides
Hot Temperature
Hormones
previtamin D(3)

Keywords

  • 14-epi-Previtamin D
  • Osteocalcin
  • Vitamin D receptor
  • Vitamin D

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry
  • Medicine(all)

Cite this

Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity. / Sawada, Daisuke; Tsukuda, Yuya; Saito, Hiroshi; Takagi, Ken ichiro; Ochiai, Eiji; Ishizuka, Seiichi; Takenouchi, Kazuya; Kittaka, Atsushi.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 121, No. 1-2, 07.2010, p. 20-24.

Research output: Contribution to journalArticle

Sawada, D, Tsukuda, Y, Saito, H, Takagi, KI, Ochiai, E, Ishizuka, S, Takenouchi, K & Kittaka, A 2010, 'Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity', Journal of Steroid Biochemistry and Molecular Biology, vol. 121, no. 1-2, pp. 20-24. https://doi.org/10.1016/j.jsbmb.2010.02.035
Sawada, Daisuke ; Tsukuda, Yuya ; Saito, Hiroshi ; Takagi, Ken ichiro ; Ochiai, Eiji ; Ishizuka, Seiichi ; Takenouchi, Kazuya ; Kittaka, Atsushi. / Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity. In: Journal of Steroid Biochemistry and Molecular Biology. 2010 ; Vol. 121, No. 1-2. pp. 20-24.
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