Synthesis and biological activity of 1a,2a,25-Trihydroxyvitamin D3

Active metabolite of 2a-(3-Hydroxypropoxy)-1a,25-dihydroxyvitamin D3 by human CYP3A4

Masashi Takano, Saori Ohya, Kaori Yasuda, Miyu Nishikawa, Akiko Takeuchi, Daisuke Sawada, Toshiyuki Sakaki, Atsushi Kittaka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Our previous studies revealed that recombinant human CYP3A4 converted 2a-(3-hydroxypropoxy)-1a,25- dihydroxyvitamin D3 (O2C3), which was a more potent binder to vitamin D receptor (VDR) than the natural hormone, 1a,25-dihydroxyvitamin D3 (1a,25(OH)2D3, 1), to 1a,2a,25-trihydroxyvitamin D3 (2). Here, we synthesized 2 using the Trost Pd-mediated coupling reaction between an A-ring precursor and a CD-ring bromoolefin and evaluated its preliminary biological activity. We found that metabolite 2 from O2C3 was still active as a VDR ligand while maintaining human VDR binding affinity (27.3% of 1a,25(OH)2D3) and HL-60 cell differentiation activity (62% of 1a,25(OH)2D3).

Original languageEnglish
Pages (from-to)182-184
Number of pages3
JournalChemical and Pharmaceutical Bulletin
Volume62
Issue number2
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP3A
Calcitriol Receptors
Metabolites
Bioactivity
HL-60 Cells
Binders
Cell Differentiation
Hormones
Ligands
dihydroxy-vitamin D3

Keywords

  • 1a,2a,25-trihydroxyvitamin D3
  • Cell differentiation
  • CYP24A1
  • CYP3A4
  • Vitamin D receptor

ASJC Scopus subject areas

  • Drug Discovery
  • Chemistry(all)

Cite this

Synthesis and biological activity of 1a,2a,25-Trihydroxyvitamin D3 : Active metabolite of 2a-(3-Hydroxypropoxy)-1a,25-dihydroxyvitamin D3 by human CYP3A4. / Takano, Masashi; Ohya, Saori; Yasuda, Kaori; Nishikawa, Miyu; Takeuchi, Akiko; Sawada, Daisuke; Sakaki, Toshiyuki; Kittaka, Atsushi.

In: Chemical and Pharmaceutical Bulletin, Vol. 62, No. 2, 02.2014, p. 182-184.

Research output: Contribution to journalArticle

Takano, Masashi ; Ohya, Saori ; Yasuda, Kaori ; Nishikawa, Miyu ; Takeuchi, Akiko ; Sawada, Daisuke ; Sakaki, Toshiyuki ; Kittaka, Atsushi. / Synthesis and biological activity of 1a,2a,25-Trihydroxyvitamin D3 : Active metabolite of 2a-(3-Hydroxypropoxy)-1a,25-dihydroxyvitamin D3 by human CYP3A4. In: Chemical and Pharmaceutical Bulletin. 2014 ; Vol. 62, No. 2. pp. 182-184.
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AU - Ohya, Saori

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AU - Sawada, Daisuke

AU - Sakaki, Toshiyuki

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